Background Respiratory failure is associated with significant morbidity and is the predominant cause of death in motor neurone disease/amyotrophic lateral sclerosis (MND/ALS). This study aimed to determine the effect of non-invasive ventilatory (NIV) support on survival and pulmonary function decline across MND/ALS phenotypes.

Methods Cohort recruited via a specialist, multidisciplinary clinic. Patients were categorised into four clinical phenotypes (ALS, flail arm, flail leg and primary lateral sclerosis) according to site of presenting symptom and the pattern of upper versus lower motor neurone involvement. NIV was initiated according to current consensus practice guidelines.

Results Between 1991 and 2011, 1198 patients diagnosed with ALS/MND were registered. 929 patients (77.5%) fulfilled the selection criteria and their data were analysed. Median tracheostomy free survival from symptom onset was 28 months in NIV-treated patients compared to 15 months in untreated (Univariate Cox regression HR=0.61 (0.51 to 0.73), p<0.001). The positive survival effect of NIV persisted when the model was adjusted for age, gender, riluzole and percutaneous endoscopic gastrostomy use (HR=0.72 (0.60 to 0.88, p=0.001). In contrast with the only randomised controlled trial, NIV statistically significantly increased survival by 19 months in those with ALS-bulbar onset (Univariate HR=0.50 (0.36 to 0.70), multivariate HR=0.59 (0.41 to 0.83)). These data confirm that NIV improves survival in MND/ALS. The overall magnitude of benefit is 13 months and was largest in those with ALS-bulbar disease. Future research should explore the optimal timing of NIV initiation within phenotypes in order to optimise respiratory function, quality of life and survival.