Current understanding and neurobiology of epileptic encephalopathies
Section snippets
Neonatal epileptic encephalopathies
The recent report of the International League Against Epilepsy (ILAE) commission on classification and terminology (Berg et al., 2010) recognizes three neonatal electroclinical syndromes: Benign Familial Neonatal Epilepsy (BFNE), Early Myoclonic Encephalopathy (EME), and Ohtahara syndrome (OS). While BFNE is a self-limited form of epilepsy associated in most cases with normal development, EME and OS are characterized by a severe disruption of cerebral functions associated with seizures, often
West syndrome
West syndrome, or Infantile Spasms (IS), is one of the most common epilepsy syndromes in the first year of life, although the overall incidence is relatively low (1 in 2000). West syndrome is characterized by the association of epileptic spasms, psychomotor regression and a specific EEG pattern called hypsarrhythmia (Fig. 3). IS result from a whole range of causes comprising focal or multifocal, pre-, peri- or postnatal brain damage or malformation, or genetic predisposition, or can occur
Dravet syndrome
Dravet syndrome (DS) is a refractory epilepsy syndrome characterized by early-onset, febrile or afebrile, generalized or unilateral, clonic or tonic–clonic seizures. Usually, the first seizures are long-lasting episodes of status epilepticus (SE) occurring during the first year of life in an otherwise normal infant. Later, myoclonus, atypical absences and partial seizures are observed. Mutations in the voltage-gated sodium channel gene SCN1A are the main genetic cause of DS (60–80% of the
Lennox-Gastaut syndrome
Lennox-Gastaut syndrome (LGS) is a childhood EE. The main clinical hallmarks of the syndrome were identified and accurately described early on (Lennox and Davis, 1950, Gastaut et al., 1966). The diagnosis is not always easy since the electroclinical characteristics appear progressively. Moreover, the term LGS has often been loosely used to define all kinds of severe childhood epilepsy syndromes (Arzimanoglou et al., 2009). This is an important clinical issue since their treatment and outcomes
EE with continuous spike-and-wave during sleep/Landau-Kleffner syndrome
EE with continuous spike-and-wave during sleep (EE-CSWS) and Landau-Kleffner syndrome (LKS) are two distinctive EEs with different clinical phenotypes. These rare epilepsy syndromes typically start with seizures around 2–4 years of age in a child with normal or moderately abnormal baseline development. Seizures are not frequent. Around age 5–6 years, severe and global neuropsychological regression occurs and seizures including head drop become usually more frequent. Both syndromes are
Role of inflammation in the neurobiology of EE
Emerging evidence highlights a putative pathogenic role of neuroinflammation, both in sustaining the recurrence of seizures and in mediating the development of long-term morbidity (Nabbout et al., 2011, Vezzani et al., 2013) (Fig. 6). Neuroinflammation is defined as an “innate immunological response of the nervous system, involving its own immune cells (microglia, astrocytes), releasing cytokines and chemokines, thus activating down-stream inflammatory effector molecules, and related molecular
Conclusion
Among the epilepsy syndromes that are considered to be EEs (Table 1), there are in our opinion not many that truly fulfill the criteria defined by Berg et al. (2010). LGS, EE-CSWS and LKS can be regarded as the best examples of this definition. In case of neonatal-onset epilepsies, the complex links between gene dysfunction and seizure activity, between gene dysfunction and cognitive involvement, and between seizures in the developing brain and cognitive outcome make it difficult to determine
References (196)
- et al.
Minocycline attenuates microglia activation and blocks the long-term epileptogenic effects of early-life seizures
Neurobiol. Dis.
(2012) - et al.
Sex-specific consequences of early life seizures
Neurobiol. Dis.
(2014) - et al.
KAINIC-acid-induced seizures — a developmental-study
Dev. Brain Res.
(1984) - et al.
Epilepsy related to developmental tumors and malformations of cortical development
Neurotherapeutics
(2014) - et al.
Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology
Lancet Neurol.
(2009) Should we still consider Dravet syndrome an epileptic encephalopathy?
Epilepsy Behav.
(2014)- et al.
Inflammation enhances epileptogenesis in the developing rat brain
Neurobiol. Dis.
(2010) - et al.
Novel animal models of pediatric epilepsy
Neurotherapeutics
(2012) - et al.
Cerebrospinal-fluid corticotropin and cortisol are reduced in infantile spasms
Pediatr. Neurol.
(1995) - et al.
Corticotropin-releasing hormone is a rapid and potent convulsant in the infant rat
Dev. Brain Res.
(1991)