Over a third had no symptoms of dysphagia

Weight loss in patients with amyotrophic lateral sclerosis (ALS) was common at diagnosis, was not accompanied by dysphagia in over one-third of patients, and affected risk of death in a dose-dependent fashion, a prospective study found.

Of 2,420 patients, 67.5% overall reported weight loss at diagnosis. Of those with weight loss, 35.1% had no symptoms of dysphagia.

Over 3,773 person-years, risk of death increased by 23% for every 10% increase in weight loss (HR 1.23, 95% CI 1.13-1.51; P<0.001), reported Leonard van den Berg, MD, PhD, of the University Medical Center Utrecht in the Netherlands, and coauthors.

In bulbar-onset ALS, about 72% of patients reported weight loss at the time of diagnosis; in spinal-onset 64.2%, and about 87% in the thoracic/respiratory onset group. The mean percent loss of body weight was 6.9% (95% CI 6.8-6.9), 5.5% (95% CI 5.5-5.6), and 11.0% (95% CI 10.8 -11.2), respectively (P<0.001).

“This population-based study shows that two-thirds of the patients with ALS have weight loss at diagnosis, which also occurs independent of dysphagia, and is related to survival,” the researchers wrote in Journal of Neurology, Neurosurgery, and Psychiatry.

“The adjusted HR for absolute weight loss in kg was 1.03 (95% CI 1.02-1.04, P<0.001), indicating that with each additional kilo of weight loss, the risk of dying during follow-up increases by 3%,” they added. “Our results suggest that weight loss is a multifactorial process that may differ from patient to patient. Gaining further insight in its underlying factors could prove essential for future therapeutic measures.”

“As the largest study to date to address the association between prediagnostic weight loss and disease duration, the authors reconfirm that patients with greater weight loss prior to diagnosis tend to have shorter survival,” noted Frederik Steyn, PhD, and Shyuan Ngo, PhD, both of University of Queensland in Australia, in an accompanying editorial.

The researchers “show that inclusion of weight loss at diagnosis improves the overall accuracy of their prediction models on survival. Confirmation of this finding has the potential to significantly advance patient care and clinical trial design,” they added.

ALS diagnosis is made when deficits in motor function lead to identification of death of both upper and lower motor neurons. Progressive paralysis, fatigue, swallowing and respiratory difficulties lead to death due to respiratory failure at a median of 3-5 years from symptom onset. There has been growing recognition of other dimensions of the disease, including cognitive changes and associated frontotemporal brain involvement.

Malnutrition is a recognized feature of ALS. A study of 121 patients on the benefit of high-calorie supplements found that about 56% of surveyed patients experienced weight loss, and about 38% of those did not have dysphagia. Percutaneous endoscopic gastrostomy supplements were beneficial for weight stabilization and quality of life.

A 2014 registry study found cumulative survival at 1, 5, and 10 years from diagnosis was 76.2%, 23.4%, and 11.8%, respectively, with longer survival predicted by variables including younger age, spinal onset, and male gender.

In the present study, van den Berg and colleagues enrolled 2,420 patients diagnosed with ALS between 2010 and 2018 in a population-based setting to determine the association between weight loss and the risk of death during follow-up.

The group overall was 57% male and average age was 65.7. Dysphagia was present at the time of diagnosis in 44.1%. Spinal-onset was most common (62.9%), followed by bulbar (33.5%) and thoracic/respiratory (3.6%). Mean body mass index at diagnosis was 24.6.

Median months of survival after diagnosis with and without weight loss were 14.7 versus 22.5 months (95% CI 13.9-15.7 and 20.5-24.7, respectively). The adjusted HR of death for no weight loss versus weight loss reported at diagnosis was 1.40 (95% CI 1.23-1.60; P<0.001).

“Interestingly, the effect of weight loss on survival did not differ significantly between patients with or without dysphagia (P=0.46), nor between bulbar and spinal onset patients (P=0.63),” the authors observed.

At diagnosis, weight loss occurred in 73.5% of those with dysphagia (mean weight loss of 7.5%) and 62.8% of those without (mean weight loss of 5.1%).

“This suggests that weight loss is not solely related to dysphagia,” the authors wrote. Potential additional factors they cited include:

  • Altered metabolism: a hypermetabolic state has been reported in 41% to 55% of the patients with ALS and may result in nutritional imbalance.
  • Altered olfaction and gustation with loss of appetite may lead to a changed dietary pattern with lower energy intake.
  • Cognitive disturbances, though the authors caution that they did not find a significant association between cognitive disturbances and weight loss in this study.
  • Secondary factors, such as loss of autonomy or effects of medication.

Because the cause of weight loss likely varies from individual to individual, future studies should determine the change in body composition rather than total weight loss, and determine details of metabolic balance, food intake, activity level, and hormonal balance, the researchers recommended. “Indeed, this multifactorial process of weight loss suggests that therapeutic interventions may also have to be individually tailored to each underlying factor,” they wrote.

Limitations of the study include the absence of data to determine the cause of weight loss.

  1. Two-thirds of the patients with ALS have weight loss at diagnosis, which also occurs independent of dysphagia and is related to survival.

  2. This study suggests that with each additional kilo of weight loss, the risk of an ALS patient dying during follow-up increased by 3%.

Paul Smyth, MD, Contributing Writer, BreakingMED™

Funding was received from the Netherlands ALS Foundation.

van den Berg reported grants from Netherlands ALS Foundation, the Netherlands Organization for Health Research and Development, and personal fees from Shire, Biogen, Cytokinetics, and Treeway.

The editorialists had no disclosures.

Cat ID: 130

Topic ID: 82,130,730,130,192,925