What is the rate of progression of Amyotrophic Lateral Sclerosis (ALS)?

Rate of Progression in Amyotrophic Lateral Sclerosis (ALS)

ALS typically progresses with an average life expectancy of 2 to 5 years from symptom onset, though there is significant individual variability with some patients living less than 2 years and approximately 5% surviving beyond a decade.1

Disease Progression Timeline

ALS progression is characterized by:

• Average survival from symptom onset: 2-5 years 1
• Median survival:
  • Recent data shows improvement to 4.32 years in contemporary cohorts compared to 3.22 years in historical groups 2
  • The Piemonte and Valle d'Aosta registry showed median survival of approximately 20.1 months from diagnosis in the most recent epoch (2011-2018) 3

Progression Patterns

Disease progression can be categorized into three main groups based on the decline rate of ALS Functional Rating Scale-Revised (ALSFRS-R) from symptom onset to diagnosis:

1. Slow progressors (below 25th percentile): <0.29 points/month decline
2. Intermediate progressors (25th-75th percentile): 0.29-1.03 points/month decline
3. Fast progressors (above 75th percentile): >1.03 points/month decline 4

Factors Affecting Progression Rate

Several factors influence the rate of ALS progression:

• Age at onset: Younger patients (<49 years) show significantly higher survival rates 5
• Site of onset:
  • Bulbar onset has poorer prognosis with faster progression
  • Spinal onset generally has slower progression 5, 1
• Respiratory function: Declining respiratory function accelerates disease progression
• Nutritional status: Weight loss and malnutrition correlate with faster progression 1

Clinical Manifestations of Progression

As ALS progresses, patients experience:

• Bulbar symptoms: Difficulty chewing, swallowing, speaking
• Respiratory decline: Increasing shortness of breath, reduced vital capacity
• Muscle weakness: Progressive weakness and atrophy in limbs
• Nutritional challenges: 8.7-13% of patients are malnourished at diagnosis, increasing to 7.5-53% during follow-up 1
• Dysphagia: Found in 6.2-85.7% of ALS patients (48.1-85.7% in bulbar form, 41.1-71.4% in spinal form) 1

Monitoring Disease Progression

Regular monitoring is essential to track progression:

• Clinical evaluations every 3 months are recommended 1
• Assessment should include:
  • Weight and BMI monitoring
  • Respiratory function tests
  • Swallowing capacity evaluation
  • ALSFRS-R scoring

Improving Survival Trends

Recent studies suggest survival may be improving:

• Contemporary patients show slower disease progression (10 months vs. 9 months to reach a 20-point increase in Appel ALS score) 2
• Survival improvement appears independent of specific ALS-modifying therapies 2
• Multidisciplinary care at specialized centers may contribute to improved outcomes 3

Outliers in Disease Progression

It's important to note that approximately:

• 6% of fast progressors live more than 5 years
• 26% of all ALS patients survive longer than 5 years
• 21% survive less than 2 years 4

These variations highlight the heterogeneous nature of ALS progression and the need for individualized prognostication.

Conclusion

While ALS remains a relentlessly progressive disease with an average survival of 2-5 years, progression rates vary significantly between individuals. Regular monitoring through specialized multidisciplinary care is essential for managing symptoms and potentially extending survival.