There is strong evidence for blood-brain and blood-spinal cord barrier dysfunction at the early stages of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Since impairment of the blood-central nervous system barrier (BCNSB) occurs during the pre-symptomatic stages of ALS, the mechanisms underlying this pathology are likely also involved in the ALS disease process. In this review, we explore how drivers of ALS disease, particularly mitochondrial dysfunction, astrocyte pathology and neuroinflammation, may contribute to BCNSB impairment. Mitochondria are highly abundant in BCNSB tissue and mitochondrial dysfunction in ALS contributes to motor neuron death. Likewise, astrocytes adopt key physical, transport and metabolic functions at the barrier, many of which are impaired in ALS. Astrocytes also show raised expression of inflammatory markers in ALS and ablating ALS-causing transgenes in astrocytes slows disease progression. In addition, key drivers of neuroinflammation, including TAR DNA-binding protein 43 (TDP-43) pathology, matrix metalloproteinase activation and systemic inflammation, affect BCNSB integrity in ALS. Finally, we discuss the translational implications of BCNSB dysfunction in ALS, including the development of biomarkers for disease onset and progression, approaches aimed at restoring BCNSB integrity and in vitro modelling of the neurogliovascular system.

AimsTo compare current trust practice to NICE clinical guideline 91. To identify patients with a history of depression or chronic physical illness on admission to acute medical services. To assess such patients for evidence of new or ongoing depression and establish prevalence of depressive symptoms in high risk patient groups. To establish appropriate pathways for referral to mental health servicesMethodsCycle one: Eligible adult medical patients were screened for self-reported symptoms of low mood and anhedonia over the 2 weeks prior to admission. Inclusion criteria required patients to have either a past history of a chronic physical health condition or a past history of depression.For those who answered “YES” to depressive symptoms, clinicians were prompted to refer to mental health services.Intervention:Screening questions were added to the adult medical clerking proforma for routine screening of admitted patients.Patients self-identifying as depressed were triaged as requiring either inpatient liaison psychiatry team support or were referred to Improving Access to Psychological Therapies (IAPT) team on discharge with GP follow up.Acute Medical departmental teaching session held on CG91 and new referral pathway created with input from liaison psychiatry team.Cycle two:Audit cycle repeated, including audit of outcomes following identification of patients with depressive symptoms.ResultsIn cycle one, of 123 patients, 90 were eligible for inclusion (PPHx depression n=39; PMHx chronic physical condition n=51).Of those with a past history of depression, 85% reported YES to current symptoms.Of patients with a chronic physical condition, without prior history of depression, 48% reported low mood or anhedonia in the past two weeks.Following introduction of electronic screening questions, completion rate by clinicians was 65% (eligible patients n=102; PPHx depression n=43; PMHx chronic physical condition n=59). 44% of patients with a chronic physical health problem self-reported symptoms of depression.After local educational meeting, 84% of identified patients had a planned referral to primary or secondary care for further mental health assessment and support.ConclusionAround half of patients with chronic physical health conditions self-report high levels of depressive symptoms, without a known mental health diagnosis or support in place.Screening of patients on admission provides an opportunity for appropriate intervention.Establishing clear referral pathways and ongoing education is needed to ensure all identified patients are referred for further assessment.