Objective: Sleep impairment is one of the most common comorbidities affecting people with epilepsy (PWE). The bidirectional relation between epilepsy and sleep has been widely established. Several studies investigated subjective sleep quality and daytime vigilance in PWE, highlighting frequent complaints of sleep fragmentation, difficulties in falling asleep, and daytime sleepiness. The present study aimed to evaluate sleep structure in drug-naive PWE, distributed on the basis of epilepsy type, and compared with controls. Methods: This observational study included adult patients newly diagnosed with epilepsy and drug-naive as well as a control group of healthy subjects. All PWE and controls underwent a dynamic 24-h EEG with signals for sleep recording to evaluate sleep architecture, structure, continuity, and fragmentation.Results: Twenty-four PWE were included and distributed in two groups based on epilepsy type. Eleven patients were included in the generalized epilepsy group (63.6% male; 34.91 ± 9.80 years) and 13 patients in the focal epilepsy group (53.8% male; 38.69 ± 12.74 years). The control group included 16 subjects (56.3% male; 32.75 ± 12.19 years). Patients with generalized or focal epilepsy had a significantly lower sleep efficiency than controls. Moreover, both patient groups presented the alteration of markers of sleep fragmentation and loss of continuity, with higher indices of sleep stage transitions and arousal. Finally, the two patient groups presented less REM sleep than controls.

Epilepsy is a common neurological disorder, affecting patients of all ages, reducing the quality of life, and associated with several comorbidities. Sleep impairment is a frequent condition in patients with epilepsy (PWE), and the relation between sleep and epilepsy has been considered bidirectional, as one can significantly influence the other, and vice versa. The orexin system was described more than 20 years ago and is implicated in several neurobiological functions other than in controlling the sleep–wake cycle. Considering the relation between epilepsy and sleep, and the significant contribution of the orexin system in regulating the sleep–wake cycle, it is conceivable that the orexin system may be affected in PWE. Preclinical studies investigated the impact of the orexin system on epileptogenesis and the effect of orexin antagonism on seizures in animal models. Conversely, clinical studies are few and propose heterogeneous results also considering the different methodological approaches to orexin levels quantification (cerebrospinal‐fluid or blood samples). Because orexin system activity can be modulated by sleep, and considering the sleep impairment documented in PWE, the recently approved dual orexin receptor antagonists (DORAs) have been suggested for treating sleep impairment and insomnia in PWE. Accordingly, sleep improvement can be a therapeutic strategy for reducing seizures and better managing epilepsy. The present review analyzes the preclinical and clinical evidence linking the orexin system to epilepsy, and hypothesizes a model in which the antagonism to the orexin system by DORAs can improve epilepsy by both a direct and a sleep‐mediated (indirect) effect.

Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy associated with numerous neurological signs and symptoms. Altered postural tone and the need for a caregiver-assisted wheelchair are features characterizing patients with LGS. Highly purified cannabidiol (CBD) is a novel antiseizure medication (ASM) recommended for seizure treatment, in combination with clobazam, in patients with LGS. Adding CBD to the previous ASM treatment helps in reducing seizure frequency, specifically drop seizures, in patients with LGS in both clinical trials and real-world studies. However, no data about drug effects on postural tone, motor activity, gait, and stability are available. In

Study Objectives Patients with isolated rapid-eye movement (REM) sleep behaviour disorder (iRBD) have an increased risk of developing neurodegenerative diseases. This study assessed cerebrospinal fluid (CSF) biomarkers of neurodegeneration and blood-brain barrier (BBB) alteration in iRBD patients compared to controls and ascertain whether these biomarkers may predict phenoconversion to alpha-synucleinopathies (Parkinson’s Disease – PD, Dementia with Lewy bodies – DLB, Multiple System Atrophy - MSA). Methods Patients and controls underwent between 2012-2016 a neurological assessment, a lumbar puncture for CSF biomarker analysis (β-amyloid42 - Aβ42; total-tau, and phosphorylated tau) and BBB alteration (CSF/serum albumin ratio). All iRBD patients were followed until 2021 and then classified into patients who converted to alpha-synucleinopathies (iRBD converters, cRBD) or not (iRBD non-converters, ncRBD). Results Thirty-four iRBD patients (mean age 67.12±8.14) and thirty-three controls (mean age 64.97±8.91) were included. At follow-up (7.63±3.40 years), eight patients were ncRBD and twenty-three patients were cRBD: eleven converted to PD, ten to DLB and two to MSA. IRBD patients showed lower CSF Aβ42 levels and higher CSF/serum albumin ratio than controls. Cox regression analysis showed that the phenoconversion rate increases with higher motor impairment (hazard ratio (HR)=1.23, p=0.032). CSF Aβ42 levels predicted phenoconversion to DLB (HR=0.67, p=0.038) and BBB alteration predicted phenoconversion to PD (HR=1.20,p =0.038). Discussion This study showed that low CSF Aβ42 levels and high BBB alteration may predict the phenoconversion to DLB and PD in iRBD patients, respectively. These findings highlight the possibility to discriminate phenoconversion in iRBD patients through CSF biomarkers, however further studies are needed.