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

Standard Treatment for Amyotrophic Lateral Sclerosis (ALS)

Riluzole 50 mg twice daily (taken at least 1 hour before or 2 hours after meals) is the foundational disease-modifying therapy for ALS, extending survival by approximately 2-3 months, and should be initiated in all patients without contraindications. 1, 2

Disease-Modifying Pharmacotherapy

First-Line Treatment: Riluzole

• Riluzole 50 mg orally twice daily is FDA-approved and extends tracheostomy-free survival with a 9% gain in probability of surviving one year (57% placebo vs 66% riluzole group). 1, 2
• Measure serum aminotransferases (liver enzymes) before starting treatment and monitor regularly during therapy, as 10-15% of patients develop ALT elevations >3 times upper limit of normal. 1, 3
• Riluzole is contraindicated in patients with baseline aminotransferase elevations >5 times upper limit of normal or active liver disease. 1
• The most common adverse effects are asthenia (18%), nausea (15%), dizziness, and gastrointestinal disorders—these are generally well-tolerated. 2, 3

Second-Line Treatment: Edaravone

• Edaravone 60 mg by slow intravenous infusion (over 60 minutes) in 28-day cycles slows loss of physical function by 33% compared to placebo. 4
• This potent free radical scavenger prevents oxidative stress-induced motor neuron death and was FDA-approved in 2017. 4
• Edaravone is particularly indicated for patients who continue to progress despite riluzole therapy. 4, 5

Emerging Therapy: Sodium Phenylbutyrate-Taurursodiol (PB-TURSO)

• PB-TURSO received conditional approval in Canada in 2022, demonstrating significant slowing of disease progression and prolonged survival. 5
• This combination targets apoptotic and cellular stress pathways in ALS. 5

Nutritional Management

Early-Stage Nutritional Support

• Assess nutritional status (BMI, weight loss) every 3 months to detect early malnutrition. 6, 7
• For muscular fatigue and prolonged mealtimes, fractionate and enrich meals with energy-dense nutrients; add oral nutritional supplementation if weight loss progresses. 6
• Perform videofluoroscopy (VFS) at diagnosis to detect early dysphagia, even in asymptomatic patients with bulbar symptoms. 7

Dysphagia Management

• For moderate dysphagia, adapt food texture (soft, semisolid, or semiliquid) based on instrumental swallowing assessment (VFS or fiberoptic endoscopic evaluation). 6
• Implement chin-tuck posture to protect the airway during swallowing. 6
• Replace thin liquids with thicker liquids and semisolid foods with high water content (like jellified water) for patients with delayed swallowing. 6

Advanced Nutritional Support

• Enteral nutrition via gastrostomy (preferably PEG) is strongly preferred over parenteral nutrition when oral intake becomes insufficient. 6, 7
• Place PEG before respiratory function significantly deteriorates (while forced vital capacity is still adequate). 7
• Parenteral nutrition should only be considered in acute settings when enteral nutrition is contraindicated, given high complication rates (3.11 per 1000 catheter days). 6

Physical Activity and Rehabilitation

• Advise low to moderate physical activity (endurance and resistance exercises) as long as it doesn't worsen the patient's condition, as evidence suggests this may slow disease progression and improve functionality. 6
• Avoid excessive physical exertion that could lead to fatigue and symptom worsening. 6

Palliative Care Integration

• Adopt a palliative care approach from the time of diagnosis, not reserved for end-stage disease. 7
• Refer early to palliative services to establish relationships with staff before communication becomes impaired and to address end-of-life issues proactively. 7

Monitoring and Safety Considerations

Hepatotoxicity Monitoring

• Monitor liver enzymes regularly during riluzole therapy; discontinue if there is evidence of liver dysfunction. 1, 3
• Patients taking other hepatotoxic drugs concurrently with riluzole may be at increased risk for hepatotoxicity. 1

Hematologic Monitoring

• Advise patients to report any febrile illness, as riluzole may rarely cause neutropenia. 1, 3

Respiratory Monitoring

• Establish baseline pulmonary function with slow vital capacity (SVC) measurements and peak cough flow (PCF) to assess airway clearance ability. 7

Critical Pitfalls to Avoid

• Do not delay riluzole initiation—the modest survival benefit (2-3 months) is most meaningful when started early in the disease course. 2, 8
• Do not use riluzole in patients with pre-existing elevated transaminases (>5x ULN), as this significantly increases hepatotoxicity risk. 1
• Do not rely solely on pharmacotherapy—nutritional support and early PEG placement are critical for maintaining quality of life and preventing aspiration complications. 6, 7
• Dysphagia management techniques effective in other conditions may not work in ALS due to the specific pathophysiology of progressive muscle atrophy and fatigue. 6