Nocturnal frontal lobe epilepsy up to now has been considered a channelopathy caused by mutations in the α 4 and β 2 subunits of the neuronal nicotinic acetylcholine receptor. However, these mutations account for on...Nocturnal frontal lobe epilepsy up to now has been considered a channelopathy caused by mutations in the α 4 and β 2 subunits of the neuronal nicotinic acetylcholine receptor. However, these mutations account for only a minority of patients, and the existence of at least a new locus for the disease has been demonstrated. In one Italian nocturnal frontal lobe epilepsy family, we identified two new putative loci on chromosomes 3 and 8, where several candidate genes are mapped. In particular, on chromosome 8, corticotropin-releasing hormone gene (CRH) appears to be a good candidate. We therefore searched for CRH mutations in the proband. The study allowed the identification of a nucle-otide variation in the promoter that was subsequently detected in all affected and obligate carrier members of the same family, in two sporadic cases, in all affected members of an additional compliant family, and in the proband of a noncompliant family. Moreover, a different mutation in the promoter was detected in a familial case. In vitro experiments showed altered levels of gene expression. CRH alterations could explain several autosomal dominant nocturnal frontal lobe epilepsy clinical features.展开更多
Background: Parkinsonian patients with excessive daytime sleepiness (EDS), hal lucinations, REM sleep behavior disorder(RBD), short mean sleep latencies, and s leep-on- set REM periods (SOREMP) on multiple sleep laten...Background: Parkinsonian patients with excessive daytime sleepiness (EDS), hal lucinations, REM sleep behavior disorder(RBD), short mean sleep latencies, and s leep-on- set REM periods (SOREMP) on multiple sleep latency tests (MSLT) have been repo rted. In these patients a narcolepsy-like pathophysiology of sleep-wake distur bances has been suggested. Patients and methods: We studied 14 consecutive patie nts with Parkinsonism and EDS. Standard studies included assessment of duration and severity of Parkinsonism (Hoehn &Yahr score),Epworth sleepiness score (ESS) , history of “REM-symptoms”(RBD/hallucinations/sleep paralysis/cataplexy-lik e episodes),polysom- nography (PSG),MSLT, and measurement of cerebrospinal fluid (CSF) levels of hy pocretin-1 (orexin A). Results:There were 12 men and 2 women (mean age 69 years ; range 54-82). The mean duration and the Hoehn &Yahr score were 6.3 years and 2.2, respectively. Diagnoses included idiopathic Parkinson’s disease (IPD, n=1 0), dementia with diffuse Lewy bodies (n=3), and multisystem atrophy (n=1). The ESS was≥10 in all patients (mean 12; range 10-18). “REM-symptoms”were repor ted by all but two patients (hallucinations: n=9; RBD:n=9).None of the patients reported cataplexy-like symptoms or sleep paralysis. On PSG sleep apnea (apnea hypopnea index > 10/h, n=7), periodic limb movements during sleep (PLMS index > 10/h, n=6), and features of RBD (n=5) were found. On MSLT mean sleep latency was < 5 minutes in 10 patients, and SOREMP were found in two patients. When compare d with controls (n=20, mean 497 pg/ml; range 350-603), CSF hypocretin-1 levels were normal in 8 patients and low in 2 patients(221 and 307 pg/ml, respectively ). Conclusion: These findings do not support the hypothesis of a “final common pathway”in the pathophysiology of narcolepsy and Parkinsonism with EDS. Sleep a pnea and PLMS may play a so-far underestimated role in the pathogenesis of EDS in Parkinsonian patients.展开更多
文摘Nocturnal frontal lobe epilepsy up to now has been considered a channelopathy caused by mutations in the α 4 and β 2 subunits of the neuronal nicotinic acetylcholine receptor. However, these mutations account for only a minority of patients, and the existence of at least a new locus for the disease has been demonstrated. In one Italian nocturnal frontal lobe epilepsy family, we identified two new putative loci on chromosomes 3 and 8, where several candidate genes are mapped. In particular, on chromosome 8, corticotropin-releasing hormone gene (CRH) appears to be a good candidate. We therefore searched for CRH mutations in the proband. The study allowed the identification of a nucle-otide variation in the promoter that was subsequently detected in all affected and obligate carrier members of the same family, in two sporadic cases, in all affected members of an additional compliant family, and in the proband of a noncompliant family. Moreover, a different mutation in the promoter was detected in a familial case. In vitro experiments showed altered levels of gene expression. CRH alterations could explain several autosomal dominant nocturnal frontal lobe epilepsy clinical features.
文摘Background: Parkinsonian patients with excessive daytime sleepiness (EDS), hal lucinations, REM sleep behavior disorder(RBD), short mean sleep latencies, and s leep-on- set REM periods (SOREMP) on multiple sleep latency tests (MSLT) have been repo rted. In these patients a narcolepsy-like pathophysiology of sleep-wake distur bances has been suggested. Patients and methods: We studied 14 consecutive patie nts with Parkinsonism and EDS. Standard studies included assessment of duration and severity of Parkinsonism (Hoehn &Yahr score),Epworth sleepiness score (ESS) , history of “REM-symptoms”(RBD/hallucinations/sleep paralysis/cataplexy-lik e episodes),polysom- nography (PSG),MSLT, and measurement of cerebrospinal fluid (CSF) levels of hy pocretin-1 (orexin A). Results:There were 12 men and 2 women (mean age 69 years ; range 54-82). The mean duration and the Hoehn &Yahr score were 6.3 years and 2.2, respectively. Diagnoses included idiopathic Parkinson’s disease (IPD, n=1 0), dementia with diffuse Lewy bodies (n=3), and multisystem atrophy (n=1). The ESS was≥10 in all patients (mean 12; range 10-18). “REM-symptoms”were repor ted by all but two patients (hallucinations: n=9; RBD:n=9).None of the patients reported cataplexy-like symptoms or sleep paralysis. On PSG sleep apnea (apnea hypopnea index > 10/h, n=7), periodic limb movements during sleep (PLMS index > 10/h, n=6), and features of RBD (n=5) were found. On MSLT mean sleep latency was < 5 minutes in 10 patients, and SOREMP were found in two patients. When compare d with controls (n=20, mean 497 pg/ml; range 350-603), CSF hypocretin-1 levels were normal in 8 patients and low in 2 patients(221 and 307 pg/ml, respectively ). Conclusion: These findings do not support the hypothesis of a “final common pathway”in the pathophysiology of narcolepsy and Parkinsonism with EDS. Sleep a pnea and PLMS may play a so-far underestimated role in the pathogenesis of EDS in Parkinsonian patients.
