Disorders of sleep and wakefulness in amyotrophic lateral sclerosis (ALS): a systematic review.

Disorders of sleep and wakefulness are common among neurodegenerative diseases. While amyotrophic lateral sclerosis (ALS) predominately manifests as motor symptoms, there is emerging evidence that disruptions to sleep and wakefulness also occur. This systematic review aims to report the most common disorders of sleep and wakefulness in ALS. We conducted a qualitative systematic review as per PRISMA guidelines and searched literature assessing the association between disorders of sleep and wakefulness with ALS using the PubMed and Medline database. Overall, 50-63% of patients with ALS have poor sleep quality as reported using the Pittsburgh Sleep Quality Index Questionnaire (PSQI). A higher proportion of ALS patients are categorized as poor sleepers, however there is conflicting evidence as to whether patients with ALS are more likely to exhibit excessive daytime sleepiness. Of the studies that utilized polysomnography, all reported various degrees of impairment to sleep microstructure and architecture among ALS patients. In future, longitudinal clinical studies will be essential for establishing the significance of impaired sleep in ALS. Future studies are also needed to establish whether the self-reported measures of poor sleep and impairment to sleep architecture occurs as a direct consequence of the disease, whether they are an early manifestation of the disease, and/or if they contribute to the neurodegenerative process.

Periconceptional ethanol exposure alters hypothalamic-pituitary-adrenal axis function, signalling elements and associated behaviours in a rodent model.

Alcohol consumption throughout pregnancy has been associated with mental illness, hyperactivity and social difficulties in offspring. This may be due in part to programmed disruption of the hypothalamic-pituitary-adrenal axis (HPA) activity and responsiveness. However, it is unknown if the HPA is affected and similar behavioural outcomes occur following alcohol exposure limited to the time around conception, the periconceptional (PC) period. Female Sprague-Dawley rats were treated with PC:EtOH (12.5 % v/v EtOH liquid diet) or a control diet from four days before conception, until embryonic day 4. Offspring at 3-months of age underwent the forced swim test (FST) and social interaction test. HPA reactivity tests (combined dexamethasone suppression test (DST) and corticotropin-releasing hormone test (CST), 30-minute restraint stress) were performed at 5 months of age and then pituitary and adrenal glands were collected for expression of genes involved in HPA regulation. PC:EtOH exposure significantly increased immobility (p < 0.05) in both sexes in the FST. PC:EtOH also increased the duration of affiliative behaviour (p < 0.05) within the social interaction test in female offspring. PC:EtOH programmed HPA hyperactivity in both sexes during the DST/CST test (p < 0.05); however, there was no impact of PC:EtOH on plasma corticosterone concentration in response to restraint stress. There was no significant impact of PC:EtOH on mRNA expression in glucocorticoid signalling genes in the pituitary gland or the steroidogenic pathway in the adrenal gland. This study suggests that alcohol exposure, even when limited to a short period around conception, can program mental illness-like phenotypes, and this was associated with alterations in HPA responsiveness. This study further highlights that consumption of alcohol even prior to implantation may impact the long-term health of offspring.