| dc.description.abstract | Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), a rare familial form of idiopathic partial epilepsy, is characterized by short nocturnal seizure episodes, occurring in stage II of the non-REM sleep. The motor attacks during the seizures and the high heritability of this disorder makes ADNFLE an intriguing topic to study. The seizures are believed to mainly originate in the frontal lobe. The onset of the disorder is often during early childhood or adolescence. However, due to the nocturnal onset of the symptoms and diagnostic difficulties, ADNFLE may be diagnosed many years after the actual disease onset. As the first epileptic disorder to have an identified genetic cause, ADNFLE is linked to genetic defects in the α4 and β2 subunit of nicotinic acetylcholine receptors (nAChR) in over hundred affected families. The mutations identified to date show a common property of hypersensitivity to ligand binding. More insights into the disease mechanism have been recently provided by animal models. In the developed mouse and rat models harboring hypersensitive nAChR mutations, important findings have been reported, including evidence for excessive glutamate transmission, developmental defects, and the paradoxal role for increased GABAergic transmission. The surprising role for GABA is probably an additional contributor in a subset of the patients.
The detailed contribution of these finding to ADNFLE pathogenesis is still poorly understood. In addition to the further research to find the consequences of developmental defects and cause of excessive glutamate transmission, more studies should be focused on the role of nicotine exposure during development and low doses of nicotine as a potent therapy. Nicotine has already been shown to be effective in a few patients, and more data on the therapeutic effects in relation to specific mutations are needed to establish nicotine as a new treatment and successor of carbamazepine. | |
