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Mutations responsible for autosomal dominant nocturnal frontal lobe epilepsy have been identified in two members of the neuronal nicotinic acetylcholine receptor gene family: CHRNA4(ENFL1 locus) and CHRNB2 (ENFL3 locus) coding for α4 and β2 subunit, respectively. However, mutations in these genes account for only a minority (less than 10%) of cases. For a third ADNFLE locus (ENFL2) on chromosome 15q24 the gene was not identified. The involvement of the three loci in the pathogenesis of ADNFLE was investigated in 12 unrelated Italian families, selected on the basis of anamnestic and video-polysomnographic data. Compliant family members were typed for polymorphic markers spanning the analyzed chromosome regions. Linkage analyses excluded association of all chromosome regions with ADNFLE in 72% of cases. In two, four and one families it was impossible to ascertain or exclude association with ENFL1, ENFL2, or ENFL3, respectively, however, no mutations have been detected in the nicotinic receptor genes located in these regions. These data strongly suggest that ENFL1, ENFL2 and ENFL3 are minor loci for the disease and point to the existence of at least a fourth locus for ADNFLE. [Copyright &y& Elsevier] more...

Context: The mechanisms underlying bone fragility and increased fracture risk observed in individuals with type 2 diabetes (T2D) are not yet fully elucidated. Previous research has suggested a role for neuropeptides in regulating bone metabolism; however, the contribution of the neuropeptide Neurotensin (NT), which is thoroughly implicated in T2D and cardiovascular disease, has not been investigated in this context., Objective: To study the relationship between circulating levels of the NT precursor proneurotensin (proNT) and bone mineralisation in T2D women., Materials and Methods: This is a cross-sectional investigation with a longitudinal prospective phase, involving 126 women with T2D who underwent bone density scans and had proNT levels measured. Biomarkers of bone metabolism and inflammation were also assessed. Data on bone mineral density (BMD) after 12 months were available for 49 patients., Main Outcome Measure: Plasma proNT levels in relation to BMD., Results: 32% of the participants had osteopenia/osteoporosis and exhibited higher proNT than those with normal BMD (200.8 ± 113.7 vs. 161.6 ± 108.8 pg/mL; p = 0.013). ProNT inversely correlated with femur BMD and T-score (p < 0.01) and was associated with degraded bone architecture (TBS, p = 0.02), and higher OPN, P1NP, TNF-α and IL-1β levels. Baseline proNT correlated with further BMD reduction at the 12-month follow-up, independently of potential confounders (p = 0.02)., Conclusions: In women with T2D, greater proNT levels are associated with impaired bone mineralisation and predict mineral density decline overtime. ProNT could potentially serve as a diagnostic tool for identifying patients at higher risk of osteopenia/osteoporosis, suggesting a significant connection between this neuropeptide and bone metabolism in diabetes., (© 2024 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.) more...

Restless Legs Syndrome/Willis Ekbom Disease (RLS/WED) is a common neurological disorder characterized by uncomfortable and unpleasant sensations in the legs, with an urge to move. The symptoms typically begin or worsen during periods of rest, in particular during the evening and at night, while the activity may typically relieve them. The majority of patients complains of poor sleep. Recent studies reported the prevalence is ranging from 5 to 10%. RLS/WED can be divided into primary (patients without associated conditions that may explain the symptoms) and secondary forms (mostly iron deficiency). RLS/WED is typically a chronic condition. The clinical course varies according to the age of onset. A great load of accumulating research and clinical data have led to an extended consensus for a need to enhance the diagnostic criteria. The aim of this paper is to provide a critical comparison among different diagnostic criteria, taking into account respectively the International Classification of Sleep Disorders (ICSD), the International RLS Study Group (IRLSSG) and the Diagnostic and Statistical Manual of Mental Disorders (DSM). There are several remarkable distinctions between the IRLSSG revised criteria, ICSD-3 and DSM-V. Contrary to the DSM-V criteria, ICSD-3 diagnostic criteria are more aligned to the IRLSSG ones. In fact, the five essential criteria of the IRLSSG are also required for the diagnosis of RLS/WED according to ICSD-3. The new IRLSSG criteria provide a more rigorous approach to case ascertainment and a better characterization of patients by specifying clinical significance and course. Future ascertainment of correct diagnosis should include documentation that all five diagnostic criteria are considered. more...

Study Objectives: To analyze cyclic alternating pattern (CAP) in restless legs syndrome (RLS) and the eventual changes induced by the acute administration of pramipexole., Setting: Sleep clinic in a scientific research institute., Interventions: Placebo or pramipexole 0.25 mg., Methods: Thirty-four patients were included: 19 patients received 0.25 mg of pramipexole and 15 were given placebo. The control group included 13 normal subjects. Nocturnal polysomnography was carried out in all subjects, and a second night was recorded after pramipexole or placebo was administered to patients with RLS. Sleep stages, CAP, and leg movement activity were scored following standard criteria., Measurements and Results: At baseline, rapid eye movement sleep latency was significantly longer in patients with RLS than in normal control subjects, and the periodic leg movement during sleep index (PLMS) was also significantly higher. On the contrary, many CAP parameters appeared to be significantly different, with a general increase in CAP rate in patients with RLS. Acute administration of pramipexole induced moderate changes in sleep architecture (increased number of stage shifts/h, sleep efficiency, and percentage of stage 2 sleep; decreased wakefulness after sleep onset; and a lower PLMS index. No effects of treatment on CAP were observed., Conclusion: Patients with RLS show significant abnormalities in sleep microstructure, represented by an excessive sleep instability/discontinuity. Acute pramipexole administration seems to exert no action on these abnormalities; the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of presleep RLS symptoms and PLMS. more...