What is the primary treatment for Amyotrophic Lateral Sclerosis (ALS)?

Primary Treatment for Amyotrophic Lateral Sclerosis (ALS)

The primary treatment for ALS consists of disease-modifying pharmacotherapy with riluzole (50-100 mg/day) or edaravone, combined with immediate initiation of multidisciplinary supportive care focused on nutritional support, respiratory management, and palliative care from the time of diagnosis. 1, 2, 3

Disease-Modifying Pharmacotherapy

Riluzole is FDA-approved for ALS treatment and remains the first-line disease-modifying agent, demonstrating a 35% decreased risk of death or tracheostomy when used at 100 mg/day over 18 months. 1, 4 The drug works through anti-excitotoxic mechanisms and has been shown to extend survival modestly in large randomized controlled trials. 4

• Dosing: 100 mg/day (50 mg twice daily) is the optimal dose based on dose-ranging studies showing significant survival benefit. 4
• Monitoring requirement: Strict monitoring of liver enzymes is mandatory, as 10-15% of patients develop alanine aminotransferase elevations more than three times the upper limit of normal. 5
• Contraindications: Active liver disease or elevated baseline transaminases. 5
• Common adverse effects: Asthenia (18%) and nausea (15%) are most frequently encountered but generally well-tolerated. 5

Edaravone (IV) is the second FDA-approved disease-modifying agent for ALS treatment, offering an alternative or potentially complementary approach. 2, 6

• Three disease-modifying treatments are currently available (riluzole, edaravone, and sodium phenylbutyrate/taurursodiol), with therapy selection based on patient characteristics. 7

Multidisciplinary Supportive Care (Initiated at Diagnosis)

A palliative care approach must be adopted from the time of diagnosis, not reserved for end-stage disease, as this improves both survival and quality of life. 3, 8 Early referral to palliative services is essential because speech and communication become severely limited in later stages. 8

Nutritional Management

• Baseline assessment: Conduct nutritional status evaluation (BMI, weight loss) every 3 months to detect early malnutrition. 3, 8
• Dysphagia screening: All patients require videofluoroscopy at diagnosis to detect early dysphagia, even if asymptomatic. 3
• Dietary modifications: 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. 3, 8, 9
• Enteral nutrition timing: Consider percutaneous endoscopic gastrostomy (PEG) placement before respiratory function significantly deteriorates, ideally when forced vital capacity (FVC) remains >50% of predicted. 8 Critical pitfall: Refuse gastrostomy when FVC falls below 30%. 8

Respiratory Management

• Baseline pulmonary function: Establish baseline with slow vital capacity (SVC) measurements and peak cough flow (PCF) to assess airway clearance ability. 3
• Non-invasive ventilation (NIV) initiation criteria: Start NIV when FVC <80% of normal with symptoms, FVC <50% predicted, or evidence of sleep-disordered breathing on polysomnography. 8
• Ventilator selection: Use bilevel positive airway pressure (BPAP) with backup respiratory rate for better patient-ventilator synchrony, particularly in patients with bulbar impairment. 8
• Important caveat: Compliance with NIV is adversely affected by cognitive impairment, requiring careful assessment before implementation. 8

Symptomatic Management

First-line therapy for sialorrhea (excessive salivation) is an inexpensive oral anticholinergic medication, with botulinum toxin therapy to salivary glands as second-line. 8

Additional symptomatic treatments address anxiety, depression, pseudobulbar affect, fasciculations, fatigue, insomnia, muscle cramps, pain, spasticity, constipation, and urinary urgency, though evidence for many pharmacologic therapies is limited. 7

Critical Pitfalls to Avoid

• Equipment delays: All requests for equipment and services for ALS should be considered urgent and handled expeditiously, as delays can result in catastrophic safety risks rather than simple inconvenience. 8
• Late PEG placement: Attempting gastrostomy when FVC <30% carries prohibitive risk. 8
• Delayed palliative care: Late referral negatively impacts patient outcomes; access should occur early in the disease course. 8
• Inadequate swallow assessment: Patients with suspected bulbar dysfunction require swallow screening before initiating oral intake, with videofluoroscopy for those with positive bedside screening or high aspiration risk. 8

Multidisciplinary Team Composition

The care team should include neurology, pulmonology, gastroenterology, speech-language pathology, nutrition, physical therapy, occupational therapy, social work, and palliative care, as multidisciplinary care improves both survival and quality of life. 8