Is survival improved by the use of NIV and PEG in amyotrophic lateral sclerosis (ALS)? A post-mortem study of 80 ALS patients

PLoS One. 2017 May 23;12(5):e0177555. doi: 10.1371/journal.pone.0177555. eCollection 2017.

Abstract

Background: Non-invasive ventilation (NIV) and percutaneous gastrostomy (PEG) are guideline-recommended interventions for symptom management in amyotrophic lateral sclerosis (ALS). Their effect on survival is controversial and the impact on causes of death is unknown.

Objective: To investigate the effect of NIV and PEG on survival and causes of death in ALS patients.

Methods: Eighty deceased ALS patients underwent a complete post mortem analysis for causes of death between 2003 and 2015. Forty-two of these patients consented for genetic testing. Effects of NIV and PEG on survival and causes of death were analyzed in a multivariable Cox proportional hazard regression.

Results: Six patients, who requested assisted suicide causing drug-induced hypoxia, were excluded from final analysis. Respiratory failure was the main cause of death in 72 out of 74 patients. Fifteen out of 74 died of aspiration pneumonia 23/74 of bronchopneumonia and 8/74 of a combination of aspiration pneumonia and bronchopneumonia. Twenty died of hypoxia without concomitant infection, and six patients had pulmonary embolism alone or in combination with pneumonia. NIV (p = 0.01) and PEG (p<0.01) had a significant impact on survival. In patients using NIV bronchopneumonia was significantly more frequent (p <0.04) compared to non-NIV patients. This effect was even more pronounced in limb onset patients (p<0.002). Patients with C9orf72 hexanucleotide repeat expansions showed faster disease progression and shorter survival (p = 0.01).

Conclusion: The use of NIV and PEG prolongs survival in ALS. This study supports current AAN and EFNS guidelines which recommend NIV and PEG as a treatment option in ALS. The risk of bronchopneumonia as cause of death may be increased by NIV.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / complications
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / mortality
  • Amyotrophic Lateral Sclerosis / therapy*
  • C9orf72 Protein
  • Cause of Death
  • Disease Progression
  • Female
  • Gastrostomy*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Noninvasive Ventilation*
  • Nuclear Respiratory Factors
  • Proportional Hazards Models
  • Proteins / genetics
  • Retrospective Studies
  • Survival Analysis

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • Nuclear Respiratory Factors
  • Proteins

Grants and funding

Christian Burkhardt receives honoraria from Biogen Idec for training courses and receives research support from the Swiss ALS Foundation and the EU Joint Programme-Neurodegenerative Disease Research (JPND) projects (grant number SNF 31ND30_141622 (SOPHIA) and 31ND30_151115 (STRENGTH)). Christoph Neuwirth receives honoraria from Biogen Idec, USA, as advisory board member tasks and training courses and support from the Swiss ALS Foundation and the EU Joint Programme-Neurodegenerative Disease Research (JPND) projects (grant number SNF 31ND30_141622 (SOPHIA) and 31ND30_151115 (STRENGTH)). Andreas Sommacal reports no disclosures. Peter M. Andersen receives honoraria from Biogen Idec and Neuroimmune for advisory board tasks and counselling on clinical trials. He receives numerous research grants from the Swedish Science Council and private foundations and patient organizations in Sweden and Norway. Markus Weber receives honoraria from Merz Pharma Schweiz AG, Biogen Idec, USA, as advisory board member and support from the Swiss ALS Foundation and the EU Joint Programme-Neurodegenerative Disease Research (JPND) projects (grant number SNF 31ND30_141622 (SOPHIA) and 31ND30_151115 (STRENGTH)).