Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models

Lateral hypothalamic neurons producing melanin-concentrating hormone (MCH) and orexin/hypocretin are involved in sleep regulation. Both MCH and orexin neurons are altered in amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disease. However, sleep alterations are currently poorly characterized in ALS, and could represent either early symptoms or late consequences of disease progression. We characterized sleep architecture using polysomnography in cohorts of both early ALS patients without respiratory impairment and presymptomatic carriers of mutations leading to familial ALS. We observed sleep alterations, including increased wake and decreased deep sleep (non-rapid eye movement—NREM3) and increased wake correlated with worse cognitive performance, in particular, verbal fluency in both cohorts. These changes in sleep architecture were replicated in three mouse models of familial ALS, Sod1G86R, FusΔNLS/+ and TDP-43Q331K mice. Altered sleep structure in mice wa..., ALS patients were recruited from the inpatient and outpatient clinics of the neurologic department of the University Hospital of Ulm, Germany. The inclusion criteria for ALS patients included a diagnosis of definite ALS based on the revised El Escorial criteria. Presymptomatic carriers of fALS genes were recruited through the study centre of the Neurological University Hospital, through which first-degree relatives of confirmed familial ALS patients receive longitudinal follow-up and counselling. Controls were recruited from the general population at the neurology clinic, and matched to ALS patients based on age, sex, and geographical location; the requirement for this group was the exclusion of neurodegenerative diseases. All individuals in the control group were unrelated to ALS or familial ALS.
The study in the ALS patient cohort was approved by the Ethics Committee of the University of Ulm (reference 391/18), as well as the study in the presymptomatic carriers which was also approve..., , # Dataset for Guillot SJ, Lang C STM paper

[https://doi.org/10.5061/dryad.gb5mkkx10](https://doi.org/10.5061/dryad.gb5mkkx10)

## Description of the data and file structure

The dataset contains the raw data from which the figures were generated.

**DATA_ALS_Cohort.csv**: sleep parameters compared between patients with ALS and their controls
Classification: classification of patients with ALS (ALS) and their controls (CTR)
ESS: Epworth Sleepiness Scale
PSQI: Pittsburgh Sleep Quality Index sumscore
ECAS_MEM: ECAS memory subscore
ECAS_SpatConpt: ECAS spatial conception subscore
ECAS_Speak: ECAS speech subscore
ECAS_VerFlnt: ECAS verbal fluency subscore
ECAS_ExecFct: ECAS executive function subscore
ECAS_Total: ECAS total sumscore
percWake: percentage of wake episodes (%)
percREM: percentage of REM episodes (%)
percNREM: percentage of NREM episodes (%)
percNREM1: percentage of NREM1 episodes (%)
percNREM2: percentage of NREM2 episodes (%)
percNREM3:percentage of NREM3 episodes (%)
Dur_N1:...