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Background: Death is the definitive hallmark of amyotrophic lateral sclerosis and primary endpoint in most treatment studies. Despite its importance limited data are available about the definitive causes of death in ALS nowadays. Previous autopsy studies (1) pointed out that defining the cause of death based solely on a clinical examination is not a reliable method to reveal the true cause of death. Treatment of our patients was according to the EFNS guidelines for patient care from 2005 (2). It is unclear if treatments such as non-invasive ventilation (NIV) or percutaneous gastrostomy (PEG) have an impact on the cause of death.
Objectives: The aim of this study was to gain a better understanding of causes of death in ALS patients and to investigate how these supportive treatments have an impact on the survival and the causes of death in ALS patients.
Methods: Seventy ALS patients were followed in our outpatient clinic and autopsied including a complete macroscopic and microscopic post mortem analysis between 2003 and 2014. Viscera for the pathological causes of death and relevant concomitant diseases were also studied. Neural tissue and CSF was stored for upcoming projects. Median time from point of death to autopsy was 4 h.
Results: In this study, the main cause of death was respiratory failure (69/70 patients). In 39/70, aspiration pneumonia and broncho-pneumonia led to death. 22//70 died of hypoxia and 5 patients requested assisted suicide inducing respiratory failure. Pulmonary embolism alone or in combination with pneumonia was detected in six. Both bulbar (n = 3) and spinal onset patients (N = 3) had embolism without any clear correlation to mobility status. A single patient died from a complication after PEG insertion. Average survival in patients using NIV was 7 month longer than without NIV and even more distinct in the NIV group comparing only limb onset patients. Bronchopneumonia was more frequent in patients using NIV versus non-NIV patients (19/38 versus 5/26, p < 0.003). The proportion of aspiration pneumonia was significantly lower in patients with PEG (7/43 versus 7/26, p < 0.003). PEG had no effect on survival or BMI at death. Genetic testing could be performed in 32 patients prior to death. Disease-causing mutations (SOD1 or C9orf72) were found in about 1/4 of this cohort.
Discussion and conclusion: In this first autopsy study after establishing of the EFNS guidelines, NIV has a positive effect on survival but may be a risk factor for bronchopneumonia. PEG insertion lowers the risk of aspiration pneumonia but has no effect on survival. No correlation was observed between pulmonary embolism and ambulatory disability or site of onset.