nocturnal epilepsy and sleepimg till 2pm

Indeed, the nAChR are extensively distributed in the brain and contribute to the regulation of sleep and arousal oscillations, at both the cortical and subcortical level. The findings of a genetic alteration of the cholinergic system and the in vivo documentation of an alteration of nAChR density distribution in ADNFLE patients may give some insights into understanding the relationships between genes, epileptogenesis, and arousal regulatory processes. To date, this is the only reported ADNFLE kindred carrying CHRNA2 mutations. In vitro studies confirmed functional alterations of the mutated protein, and postmortem brain examination disclosed a high expression of CHRNA2 in thalamic structures. These patients exhibited prominent fear and organized motor behaviors, which led the authors to speculate that seizures could have a fronto-limbic involvement. Ī fourth locus was mapped on chromosome 8p21.2-8q12 in 2006 in an Italian family and a mutation was identified in the α2 subunit of the nAChR ( CHRNA2) gene (Table 1). Further CHRNB2 mutations were disclosed in different unrelated families and one sporadic case (Table 1) in two families a coexistence of both epilepsy and specific deficits in tasks of verbal memory was observed in two patients ictal single-photon emission computed tomography showed a significant hyperperfusion of the cingulated gyrus. In particular, a second locus was identified at chromosome 15q24 in one family and a third locus spanning the pericentromeric region of chromosome 1 was identified in an Italian ADNFLE family, the latter containing the gene coding for the β2 subunit of the nACh receptor (CHRNB2) (Table 1). ADNFLE was quickly recognized as a genetically heterogeneous disorder as most of the described families did not show mutations in the CHRNA4 gene, and new loci and genes were reported in the following years. Three de novo or inherited CHRNA4 mutations, occasionally associated with mild-to-moderate mental retardation were later reported.

With the identification of these mutations, subsequently confirmed in families of different origins, ADNFLE became the first epilepsy in which genetic bases were detected, apparently showing features of a monogenic disease. Both mutations were shown to have major effects on receptor function in vitro. More specifically, a locus was identified at chromosome 20q13.2-q13.3 and two different mutations were detected in the gene coding the α4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) (CHRNA4). The genetic origin of the disease was confirmed by a linkage study in Australian kindred. After the report of several families showing a clear autosomal dominant inheritance, autosomal dominant NFLE (ADNFLE) was introduced as a distinct clinical entity with marked intrafamilial variability in disease severity. All the aforementioned issues will be reviewed and discussed in the following sections in order to give a comprehensive overview of the pathophysiological and clinical aspects of NFLE.Ī family history for epilepsy is frequently observed in NFLE patients. NFLE is usually considered a benign clinical epileptic syndrome because seizures occur almost exclusively during sleep, and in the majority of patients the pharmacological treatment is effective however, severe and drug-resistant forms, occasionally associated with mental retardation, have been described. In addition, a genetic heterogeneity is also evident within the familial type. It is now recognized that NFLE is not a homogeneous disease as familial, idiopathic, sporadic, cryptogenetic, or symptomatic forms do exist. In the last few decades, the spread and refinement of video–polysomnographic (V-PSG) technology has allowed NFLE to be fully defined and described, so that it is now considered a distinct epileptic syndrome nevertheless, some NFLE case can be hardly distinguishable from non-rapid eye movement (NREM) parasomnias and from sleep-related epileptic seizures originating outside the frontal lobe. The definition of nocturnal frontal lobe epilepsy (NFLE) has been introduced in order to identify patients affected by frontal lobe epilepsy whose seizures are almost exclusively sleep related. Seizures originating from the frontal lobe mainly occur during sleep.

Nocturnal epilepsy and sleepimg till 2pm