Defining novel functions for cerebrospinal fluid in ALS pathophysiology

Despite the considerable progress made towards understanding ALS pathophysiology, several key features of ALS remain unexplained, from its aetiology to its epidemiological aspects. The glymphatic system, which has recently been recognised as a major clearance pathway for the brain, has received considerable attention in several neurological conditions, particularly Alzheimer's disease. Its significance in ALS has, however, been little addressed. This perspective article therefore aims to assess the possibility of CSF contribution in ALS by considering various lines of evidence, including the abnormal composition of ALS-CSF, its toxicity and the evidence for impaired CSF dynamics in ALS patients. We also describe a potential role for CSF circulation in determining disease spread as well as the importance of CSF dynamics in ALS neurotherapeutics. We propose that a CSF model could potentially offer additional avenues to explore currently unexplained features of ALS, ultimately leading to new treatment options for people with ALS.</p

Loneliness among people with substance use problems: a narrative systematic review

Issues: Despite the serious implications of loneliness on health and wellbeing, little is understood about this experience across people with substance use problems. This systematic review aimed to examine: (i) correlates and predictors of loneliness; (ii) theories underpinning loneliness; (iii) methods employed to measure loneliness; and (iv) loneliness interventions for people with substance use problems. Approach: Empirical sources were identified from key databases for all publications preceding February 2019. Overall, 41 studies met the eligibility criteria and were included in the review. Key Findings: Findings from this review suggest that loneliness is related to poor physical and mental health, substance use, the quality of relationships, stigma and perception of ill treatment by others. Although cognitive theories have proposed cognitive patterns underlying the onset and maintenance of loneliness, they had not been investigated in relation to measurement or intervention efforts. Just one loneliness measure (UCLA Loneliness Scale) is valid for use with this population. Finally, only a single loneliness intervention had been trialled and was not found to be efficacious in reducing loneliness for people with substance use problems. Implications: Understanding possible links between loneliness and substance use and how to alleviate loneliness is important for this population in terms of their wellbeing and recovery. Conclusion: Loneliness is prevalent and experienced as problematic among people with substance use problems. Future research should focus on employing longitudinal designs, using validated, multidimensional measures of loneliness and on developing and trialling loneliness interventions that meet the specific needs of people with substance use problems