Primary Treatment for Amyotrophic Lateral Sclerosis (ALS)
The primary treatment for ALS is multidisciplinary care centered on improving quality of life and prolonging survival, with riluzole (50 mg twice daily) as the only FDA-approved disease-modifying medication that modestly slows progression, combined with early palliative care, respiratory support, and nutritional management. 1
Disease-Modifying Pharmacotherapy
Riluzole remains the cornerstone pharmacologic treatment, approved by the FDA for ALS with a recommended dosage of 50 mg twice daily, taken at least 1 hour before or 2 hours after meals 1. This antiglutamatergic agent decreases the risk of death or tracheostomy by approximately 35% when adjusted for baseline prognostic factors, though the survival benefit is modest (approximately 2-3 months) 2. Riluzole demonstrates a dose-related decrease in risk of death or tracheostomy over 18 months 2.
Additional FDA-approved agents include edaravone (administered as 60 mg IV infusion over 60 minutes in 28-day cycles), which slows loss of physical function by 33% compared to placebo, and sodium phenylbutyrate/taurursodiol (PB/TURSO) 3, 4. However, riluzole remains first-line due to its oral administration, established safety profile, and cost-effectiveness 5, 6.
Critical monitoring requirement: Measure serum aminotransferases before and during riluzole treatment, as hepatotoxicity is a significant concern 1. Discontinue riluzole if baseline elevations exceed 5 times the upper limit of normal or if evidence of liver dysfunction develops 1.
Multidisciplinary Care Framework
The National Academies of Science, Engineering, and Medicine (NASEM) 2024 guidelines emphasize that multidisciplinary care is not optional but essential, as it improves both survival and quality of life 7, 8. The care team must include neurology, pulmonology, gastroenterology, speech-language pathology, nutrition, physical therapy, occupational therapy, social work, and palliative care 8.
Key Components of Multidisciplinary Management:
Respiratory Management:
- Initiate non-invasive ventilation (NIV) when FVC falls below 80% of normal with symptoms, FVC <50% predicted, or evidence of sleep-disordered breathing 8
- Use bilevel positive airway pressure (BPAP) with backup respiratory rate for patients with bulbar impairment, as recommended by the American College of Chest Physicians 8
- Critical timing: Respiratory assist device (RAD) placement should occur before FVC falls below 50% of predicted, and gastrostomy should be refused when FVC falls below 30% 7, 8
Nutritional Support:
- Conduct nutritional status assessment (BMI, weight loss) every 3 months to detect early malnutrition 8, 9
- For dysphagia, adapt food texture to facilitate swallowing, implement chin-tuck postural maneuvers, and use thicker liquids and semisolid foods with high water content instead of thin liquids 8, 10
- All patients with suspected bulbar dysfunction require swallow screening before initiating oral intake; those with positive screening require videofluoroscopy swallowing study (VFSS) 8, 9
- Percutaneous endoscopic gastrostomy (PEG) placement should occur before respiratory function significantly deteriorates, ideally when FVC remains >50% of predicted 8
Bulbar Symptom Management:
- First-line therapy for sialorrhea is an inexpensive oral anticholinergic medication 8
- Second-line therapy is botulinum toxin injection to salivary glands 8
Palliative Care Integration
A palliative care approach must be adopted from the time of diagnosis, not reserved for end-stage disease 7, 8, 9. Early referral to palliative services is essential because speech and communication become severely limited in later stages 8. This represents a fundamental shift from traditional models that delay palliative involvement until terminal phases.
The American Academy of Neurology specifically recommends establishing relationships with palliative care staff early, before communication becomes impaired 9. Initiate end-of-life discussions at specific trigger points: presence of patient distress, evolution of disease, or expressed desire of the patient to discuss these issues 8.
Critical Pitfalls to Avoid
Equipment and service delays can result in catastrophic safety risks rather than simple inconvenience 7. The rapidly progressive nature of ALS (average life expectancy 2-5 years from onset, 25-28 months for bulbar-onset) does not fit traditional reimbursement models predicated on slower timelines 7, 8. All requests for equipment and services for ALS should be considered urgent and handled expeditiously 8.
Compliance with NIV is adversely affected by cognitive impairment, requiring careful assessment before implementation 8. Patients with executive dysfunction are at higher risk of falls, choking episodes, and injuries 8.
Late palliative care referral negatively impacts patient outcomes 8. Access to palliative care and hospice services should occur early in the disease course, not when death is imminent 8.
Prognosis and Disease Course
Bulbar-onset ALS has significantly worse outcomes compared to spinal-onset, with median survival of 28 months versus 44 months for spinal-onset patients with dysphagia 8. Aspiration pneumonia occurs in 11.4-13% of bulbar ALS cases and represents a leading cause of mortality 8. There is currently no cure for ALS, and approximately 90% of cases are sporadic without a known genetic mutation 7.