Theme 10 Disease stratification and phenotyping of patients

Abstract

Background: MND is a progressive neurodegenerative disease characterised by death of upper and lower motor neurons, leading to progressive weakness of the bulbar, limb, thoracic and abdominal muscles. MND has a fairly stereotypical course, with death from respiratory failure occurring 2-4 years after symptom onset in most cases (1). Making the diagnosis of MND can be straightforward when key clinical criteria are met; however, at first presentation, rarely do patients meet these criteria, neurological changes may be subtle and disease progression slow. Thus, diagnosis poses a significant challenge, particularly in general practice, where patients are most likely to first present. Not surprisingly, there is usually a delay of 10-18 months between symptom onset and MND diagnosis (2). Importantly, early assessment by a neurologist is associated with a shorter time to MND diagnosis (3), which has significant implications for access to healthcare, including Riluzole and multidisciplinary clinics, which improve survival (4). Although delay in diagnosis is well documented, there have been no studies that have sought to identify factors associated with time to diagnosis, thereby enabling targeted implementation of a public health intervention.Objectives: To characterise the clinical factors that influence time to diagnosis of MND.Methods: 112 patients with MND attending the Southern Adelaide MND Clinic enrolled between January 2016 - 2018 were retrospectively recruited in to a cohort study. Information pertaining to the patient's demographics and their journey to diagnosis collected by a specialist physician and stored in the Australian MND Registry during clinic review were analysed to identify factors associated with time to diagnosis.Results: Mean time to diagnosis was 13 ± 1 months (range 1 - 38 months) from symptom onset. 41% of patients were classified as having fast disease progression; compared to those with slow disease progression, these patients were diagnosed earlier (8 ± 1 months vs 16 ± 2 months) (p < 0.0001, t = 34.6, df =220), were less likely to undergo multiple specialist opinions prior to referral to a neurologist (53% vs 73%) (p < 0.05, Chi-squared = 9.5, df =1), and were more disabled at time of diagnosis (mean ALSFRS-R 33 ± 5 vs ALSFRS-R 41 ± 5) (p < 0.0001, t = 12.4, df =220).Discussion and conclusions: Fast disease progression identifies a dichotomy of MND patients diagnosed earlier, although more disabled at diagnosis, likely mediated by a more efficient referral process. A greater awareness of MND is required to shorten time to diagnosis.