What is the recommended treatment plan for a patient diagnosed with Amyotrophic Lateral Sclerosis (ALS)?

Treatment of Amyotrophic Lateral Sclerosis (ALS)

ALS requires immediate initiation of riluzole 50 mg twice daily (taken at least 1 hour before or 2 hours after meals) combined with early multidisciplinary palliative care, nutritional support, and respiratory management to maximize survival and quality of life. 1, 2

Disease-Modifying Pharmacotherapy

Riluzole (First-Line Treatment)

• Riluzole 50 mg orally twice daily is the primary disease-modifying therapy and should be offered to all patients with ALS to slow disease progression 1, 3
• Prolongs survival by approximately 2-3 months, with a 9% gain in probability of surviving one year (from 57% to 66%) 4
• Must be taken at least 1 hour before or 2 hours after meals for optimal absorption 1
• Measure serum aminotransferases (ALT/AST) before starting treatment and monitor regularly during therapy 1, 3
• Do not use if baseline aminotransferases are greater than 5 times upper limit of normal 1
• Discontinue if evidence of liver dysfunction develops (10-15% of patients develop ALT elevations >3x upper limit of normal) 5, 1
• Most common adverse effects are asthenia (18%), nausea (15%), dizziness, decreased lung function, and abdominal pain 1, 5
• Advise patients to report any febrile illness due to risk of neutropenia 1

Edaravone (Alternative/Adjunctive Therapy)

• FDA-approved for treatment of ALS 6
• Administered as 60 mg intravenous infusion over 60 minutes 6
• Initial treatment cycle: daily dosing for 14 days followed by 14-day drug-free period 6
• Subsequent cycles: daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods 6
• Contraindicated in patients with hypersensitivity to edaravone or sodium bisulfite 6
• Most common adverse reactions include contusion, gait disturbance, and headache 6

Nutritional Management

Assessment and Monitoring

• Assess nutritional status (BMI, weight) every 3 months to detect early malnutrition 2, 7
• Target weight gain if BMI <25 kg/m², weight stabilization if BMI 25-35 kg/m² 2
• Perform videofluoroscopy at diagnosis to detect early dysphagia, even in asymptomatic patients, particularly those with bulbar symptoms 8, 7

Dysphagia Management

• For patients with muscular fatigue and prolonged meals, fractionate meals and enrich with high-calorie foods 8
• Modify food texture to soft, semisolid, or semiliquid states to compensate for poor oral preparation and ease transport while avoiding choking 8, 2
• Use thicker liquids and jellified water instead of thin liquids to prevent aspiration 8, 2
• Implement chin-tuck posture during swallowing to protect airways and prevent laryngeal penetration 8, 2
• Use head rotation for hypertonicity, incomplete release, or premature upper esophageal sphincter closure 8, 2
• Hyperextended head posture only if lingual pump is absent and safe transit is ensured 8, 2
• Throat clearing every 3-4 swallows to prevent post-swallowing inhalation 8, 2
• Add dietary fiber for constipation caused by abdominal weakness 8, 2

Oral Nutritional Supplementation

• Recommend oral nutritional supplements for patients who cannot meet requirements with enriched diet alone 8
• High-calorie/high-protein supplements (300 kcal and 18g protein per unit) may be beneficial 8
• Insufficient evidence that oral supplementation alone improves survival 8

Enteral Nutrition

• Consider percutaneous endoscopic gastrostomy (PEG) to stabilize weight and prolong survival 3
• PEG should be placed before respiratory function significantly deteriorates (ideally when forced vital capacity >50%) 7
• Enteral nutrition is preferred over parenteral nutrition in all cases except acute contraindications (gastrointestinal hemorrhage, ileus, gastrostomy placement failure) 8
• Home parenteral nutrition is generally not indicated and carries significant risks including catheter-related bloodstream infections 8

Respiratory Management

Monitoring and Assessment

• Establish baseline pulmonary function with slow vital capacity (SVC) measurements and peak cough flow (PCF) 7
• Monitor respiratory function regularly to detect decline early 3

Non-Invasive Ventilation (NIV)

• NIV should be considered to treat respiratory insufficiency to lengthen survival and slow decline of forced vital capacity 3
• NIV may improve quality of life 3
• Early initiation of NIV increases compliance 3
• Assess cognitive function before recommending NIV, as cognitive impairment reduces compliance 2

Airway Clearance

• Insufflation/exsufflation devices should be considered to help clear secretions 3

Invasive Mechanical Ventilation

• Requires careful advance planning, as only 4-9% of patients choose this option 2
• Discuss preferences early in disease course before communication becomes limited 2

Palliative Care Integration

Timing and Approach

• Adopt a palliative care approach from the time of diagnosis, not reserved for end-stage disease 2, 7
• Early referral to palliative services is essential to establish relationships with staff and address end-of-life issues before communication becomes limited 2, 7
• Multidisciplinary care improves both survival and quality of life 2

Advance Care Planning

• Initiate advance directive discussions early in disease course, ideally at diagnosis 2
• Address preferences regarding ventilatory support, feeding tubes, and end-of-life care 2
• Only 30% of patients complete advance directives despite 78% of centers considering them useful 2

Cognitive Assessment

• Screen all patients for cognitive impairment, as up to 40% have cognitive dysfunction that impacts treatment decisions and prognosis 2
• Cognitive impairment reduces likelihood of choosing long-term mechanical ventilation and decreases NIV compliance 2

Caregiver Support

• Implement structured caregiver support from diagnosis, including counseling, support groups, and crisis management systems 2
• Behavioral deficits in ALS patients have significant negative impact on caregivers' quality of life 2

Symptomatic Management

Sialorrhea

• Anti-muscarinic therapy or botulinum toxin A can manage excessive saliva 8, 2
• No evidence links sialorrhea treatment with dysphagia improvement 8

Physical Activity

• Endurance and resistance exercises may slow disease progression and improve quality of life as long as they do not worsen physical state 8

Critical Pitfalls to Avoid

• Late referral to palliative services is the most common and harmful error, negatively impacting quality of life for patients and caregivers 2
• Delaying PEG placement until respiratory function is severely compromised increases procedural risk 7
• Failing to monitor liver enzymes in patients on riluzole can lead to serious hepatotoxicity 1, 5
• Not assessing cognitive function before recommending NIV leads to poor compliance 2
• Waiting for symptomatic dysphagia before performing videofluoroscopy misses early swallowing dysfunction 8, 7