Razionale sull'impiego del fenofibrato come terapia aggiuntiva nell'epilessia frontale notturna (NFLE) farmacoresistente

Nocturnal Frontal Lobe Epilepsy (NFLE) is characterized by onset during infancy or childhood with persistence in adulthood, family history of similar nocturnal episodes simulating non-REM parasomnias (sleep terrors or sleepwalking), general absence of morphological substrates, often by normal interictal electroencephalographical recordings (EEGs) during wakefulness. A family history of epilepsy may be present with Mendelian autosomal dominant inheritance has been described in some families. Recent studies indicate the involvement of neuronal nicotinic acetylcholine receptors (nAChRs) in the molecular mechanisms of NFLE. Mutations in the genes encoding for the α4 (CHRNA4) and ß2 (CHRNB2) subunits of the nAChR induce changes in the biophysical properties of nAChR, resulting generally in a “gain of function”. Preclinical studies report that activation of a nuclear receptor called type peroxisome proliferator-activated receptor (PPAR-α) by endogenous molecules or by medications (e.g. fenofibrate) reduces the activity of the nAChR and, therefore, may decrease the frequency of seizures. Thus, we hypothesize that negative modulation of nAChRs might represent a therapeutic strategy to be explored for pharmacological treatment of this form of epilepsy, which only partially responds to conventional antiepileptic drugs. In fact, carbamazepine, the current medication for NFLE, abolishes the seizures only in one third of the patients. The aim of the project is: 1)_to verify the clinical efficacy of adjunctive therapy with fenofibrate in pharmacoresistant NFLE and ADNFLE patients; focousing on the analysis of the polysomnographic action of the PPAR- agonist (fenofibrate). 2)_to demonstrate the subtended mechanism of efficacy by means of electrophysiological and behavioral experiments in an animal model of the disease: particularly, transgenic mice carrying the mutation in the nAChR 4 subunit (Chrna4S252F) homologous to that found in the humans. Given that a PPAR-α agonist, FENOFIBRATE, already clinically utilized for lipid metabolism disorders, provides a promising therapeutic avenue in the treatment of NFLE\ADNFLE

EEG functional network topology is associated with disability in patients with amyotrophic lateral sclerosis

Amyotrophic Lateral Sclerosis (ALS) is one of the most severe neurodegenerative diseases, which is known to affect upper and lower motor neurons. In contrast to the classical tenet that ALS represents the outcome of extensive and progressive impairment of a fixed set of motor connections, recent neuroimaging findings suggest that the disease spreads along vast non-motor connections. Here, we hypothesised that functional network topology is perturbed in ALS, and that this reorganization is associated with disability. We tested this hypothesis in 21 patients affected by ALS at several stages of impairment using resting-state electroencephalography (EEG) and compared the results to 16 age-matched healthy controls. We estimated functional connectivity using the Phase Lag Index (PLI), and characterized the network topology using the minimum spanning tree (MST). We found a significant difference between groups in terms of MST dissimilarity and MST leaf fraction in the beta band. Moreover, some MST parameters (leaf, hierarchy and kappa) significantly correlated with disability. These findings suggest that the topology of resting-state functional networks in ALS is affected by the disease in relation to disability. EEG network analysis may be of help in monitoring and evaluating the clinical status of ALS patients

Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort

Introduction Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naive patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). Methods We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. Results One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. Conclusion Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach

Restless Legs Syndrome/Willis-Ekbom Disease and Periodic Limb Movements in Sleep in the Elderly with and without Dementia

There is great interest in the study of sleep in healthy and cognitively impaired elderly. Sleep disorders have been related to quality of aging. Sleep-related movements are a frequent cause of disordered sleep and daytime sleepiness. Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is often unrecognized in the elderly. This review explores RLS/WED in the elderly population. The elderly population may be subdivided into 3 groups: healthy, dependent, and frail. The RLS/WED could be a predictor for lower physical function; its burden on quality of life and health care-related costs, in the elderly, should be an important clinical and public health concern

Sleep and violence

Treatment of violent behaviors in sleep depends on the underlying condition and a correct identification of the causative disorder is mandatory. After eliminating possible precipitating factors, pharmacological treatment is often required to control violent sleep behaviors. Although no drugs are specifically approved for the treatment of parasomnias and placebo-controlled trials are lacking in these patient populations, clonazepam is considered the drug of choice in the management of both Non-REM and REM parasomnias. Benzodiazepines may cause unwanted side effects especially in older individuals and tolerance is sometime observed. Melatonin and pramipexole may represent alternative options in REM sleep behavior disorder. Hypnosis therapy may be considered in arousal disorders when pharmacological treatment is contraindicated or ineffective. Management of nocturnal frontal lobe epilepsy include a first-step pharmacological approach with antiepileptic drugs (eg, carbamazepine, oxcarbazepine or other drugs effective on partial seizures), but surgical options may be considered in drug refractory patients. The published evidence for the efficacy of various treatments relies mostly upon case series or case reports

Firing a loaded gun during sleep in an elderly man with a "perfect storm" of risk factors including severe obstructive sleep apnea

We report a case of firing a loaded gun during sleep in a geriatric patient with undiagnosed major sleep disorders and multiple risk factors for sleep violence. Polysomnographic findings, diagnostic challenges, and forensic implications in this unprecedented geriatric case are discussed

Vagal nerve stimulation effects on cerebellar tremor in multiple sclerosis

Although vagal nerve stimulation (VNS) is a common alternative add-on treatment for epilepsy, the effects of the possible combination of VNS programmable options other than those established in antiepileptic protocols (e.g., current intensity, on-off operating time) have not been fully investigated. This study reports the effect of low-intensity, low cycling VNS on a subject with persistent cerebellar tremor due to multiple sclerosis (MS)