What is the primary treatment for amyotrophic lateral sclerosis (ALS)?

Primary Treatment for Amyotrophic Lateral Sclerosis (ALS)

Riluzole 100 mg daily (50 mg twice daily) is the primary pharmacologic treatment for ALS, prolonging survival by approximately 2-3 months, and should be initiated in all patients with definite or probable ALS who can tolerate it. 1, 2, 3

Disease-Modifying Pharmacotherapy

Riluzole (First-Line Treatment)

• Riluzole 50 mg twice daily (100 mg/day total) is FDA-approved and represents the standard of care for ALS treatment. 1
• This dose provides a 9% absolute gain in probability of surviving one year (57% placebo vs 66% riluzole), with a hazard ratio of 0.80 (95% CI 0.64-0.99). 2, 3
• Survival benefit is significant at 6,9,12, and 15 months, though not at 3 or 18 months. 3
• The 100 mg dose demonstrates the best benefit-to-risk ratio compared to 50 mg or 200 mg doses. 2

Edaravone (Second-Line or Adjunctive Treatment)

• Edaravone injection 60 mg IV is FDA-approved for ALS treatment, administered over 60 minutes according to a specific cycling schedule. 1
• Dosing schedule: Initial cycle with daily dosing for 14 days followed by 14-day drug-free period, then subsequent cycles with 10 days of dosing out of 14-day periods. 1
• In clinical trials, edaravone slowed decline in ALSFRS-R scores by 2.49 points compared to placebo at 24 weeks (p=0.0013). 1
• Efficacy was established in patients who retained most activities of daily living (ALSFRS-R ≥2 on each item), had normal respiratory function (FVC ≥80%), and disease duration ≤2 years. 1

Critical Monitoring for Riluzole

Hepatotoxicity Surveillance

• Monitor serum transaminases (ALT/AST) before treatment initiation, monthly for the first 3 months, then every 3 months during the first year. 4, 5
• Elevated liver enzymes are the most common reason for discontinuation (5.4% of patients). 4
• Threefold increase in serum alanine transferase occurs more frequently with riluzole (weighted mean difference 2.69,95% CI 1.65-4.38). 3
• Most transaminase elevations are transient and regress within 2-6 months of continued treatment. 5

Other Adverse Events Requiring Monitoring

• All adverse events with riluzole occur within the first 6 months of treatment and improve after discontinuation. 4
• Common dose-dependent adverse effects include: asthenia, dizziness, gastrointestinal disorders (nausea, vomiting, diarrhea, anorexia), circumoral paresthesia, and somnolence. 2, 5
• Perform chest X-rays as clinically indicated during the first 6 months, as interstitial pneumonia can occur and may require steroid treatment. 4

Essential Multidisciplinary Management Framework

Beyond pharmacotherapy, multidisciplinary care is essential and improves both survival and quality of life. 6, 7

Core Team Composition

• The care team must include: neurology, pulmonology, gastroenterology, speech-language pathology, nutrition, physical therapy, occupational therapy, social work, and palliative care. 6

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. 6
• Use bilevel positive airway pressure (BPAP) with backup respiratory rate for patients with bulbar impairment. 6
• Establish baseline pulmonary function with slow vital capacity (SVC) measurements and peak cough flow (PCF) at diagnosis. 8

Nutritional Support

• Conduct nutritional status assessment (BMI, weight loss) every 3 months to detect early malnutrition. 8, 6
• Perform videofluoroscopy at diagnosis for all patients with bulbar symptoms to detect early dysphagia, even if asymptomatic. 8
• Place percutaneous endoscopic gastrostomy (PEG) before FVC falls below 50% of predicted; refuse gastrostomy when FVC <30%. 6, 7
• For dysphagia, adapt food texture, implement chin-tuck postural maneuvers, and use thicker liquids and semisolid foods with high water content. 6, 7

Palliative Care Integration

• Adopt a palliative care approach from the time of diagnosis, not reserved for end-stage disease. 8, 6, 7
• Early referral to palliative services is essential because speech and communication become severely limited in later stages. 6, 7
• Initiate end-of-life discussions at specific trigger points: patient distress, disease evolution, or patient's expressed desire to discuss these issues. 6, 7

Critical Pitfalls to Avoid

• Do not delay equipment and service requests—all requests for ALS patients should be considered urgent and handled expeditiously, as delays can result in catastrophic safety risks. 7
• Do not wait for advanced respiratory decline before PEG placement; optimal timing is when FVC remains >50% predicted. 6, 7
• Do not delay palliative care referral until end-stage disease; late referral negatively impacts patient outcomes. 7
• Carefully monitor the first 6 months of riluzole treatment through interviews, chemical analyses, and chest X-rays as required. 4