{
  "abstract": "Introduction The gut-brain axis (GBA) has been suggested as a potentially modifiable pathway for preventing and slowing progression of motor neuron disease (MND). MND is a rapidly-progressing, fatal neurodegenerative disorder with a poorly understood pathogenesis and limited disease modifying options. The lack of reliable predictors of disease progression is a major unmet need in the management of MND patients.Methods A prospective longitudinal cohort study was conducted following participants through administration of questionnaires from baseline up until a maximum of 18 months at approximate 6-month intervals. Gastrointestinal, psychological, dietary, quality of life (QOL), and sleep-related factors associated with change in Amyotrophic Lateral Sclerosis (ALS) Functional Rating Scale-Revised (ALSFRS-R) scores over time were examined. ALSFRS-change (defined as ALSFRS-R score at last visit subtracted from baseline score, and divided by time interval in months), was used as a measure of disease progression. In the first analysis, baseline demographic and clinical characteristics were compared between MND patients (n = 113), healthy controls (HCs; n = 39), and Kennedy’s disease (KD) neurological controls (NCs; n = 21). In the second analysis, baseline questionnaire scores were then compared between the same three groups. In the final analysis, the associations of demographic, clinical variables, and questionnaire scores with ALSFRS-change in MND patients (n = 38) were assessed using univariate linear regression analyses.Results The first analysis indicated that MND patients were significantly older (p < 0.001) than HCs, and significantly older (p < 0.001) at disease onset, with shorter diagnostic delay (p < 0.001) and faster disease progression (p < 0.001) than NCs.The second analysis showed that MND patients scored significantly worse than HCs for ALSFRS-R, Constipation Scoring System (p = 0.006), Gastrointestinal Symptom Rating Scale (GSRS; p = 0.028), Swallowing Disturbance Questionnaire (p < 0.001), Gastrointestinal Quality of Life Index (GIQLI; p < 0.001), Patient Health Questionnaire-9 for depression (p = 0.035), EQ-5D QOL self-report and index score (p < 0.001), and Pittsburgh Sleep Quality Index (PSQI; p = 0.014). MND patients only scored significantly worse than NCs for ALSFRS-R fine motor skills subscore (p = 0.016).The univariate regression analyses with ALSFRS-change revealed several significant predictors of disease progression (p < 0.05): GSRS-change, GIQLI-change, EQ-5D QOL self-report and index score change, and PSQI change.Conclusions Longitudinal changes in gastrointestinal symptoms, sleep quality, and overall QOL are associated with disease progression in MND. These findings support a role for GBA-related factors in MND and suggest that non-motor features may contribute useful prognostic information. Future studies to determine if targeting these pathways could improve future management strategies are needed.",
  "authors": [
    {
      "affiliations": [
        "Queen Mary University of London, London, United Kingdom"
      ],
      "name": "Iman Khwaja"
    },
    {
      "affiliations": [
        "Queen Mary University of London, London, United Kingdom"
      ],
      "name": "Helen R Warren"
    },
    {
      "affiliations": [
        "University College London, London, United Kingdom"
      ],
      "name": "Andrea Malaspina"
    },
    {
      "affiliations": [
        "Queen Mary University of London, London, United Kingdom"
      ],
      "name": "Qasim Aziz"
    }
  ],
  "title": "P388 Characterisation of the role of the gut-brain axis in the progression of motor neuron disease",
  "uid": "70ea5e3c-f02b-5bff-b5e6-602ade8957d8"
}