What is the management and treatment of amyotrophic lateral sclerosis (ALS)?

Management and Treatment of Amyotrophic Lateral Sclerosis (ALS)

Pharmacological Treatment

Riluzole 50 mg twice daily (taken at least 1 hour before or 2 hours after meals) is the only FDA-approved disease-modifying therapy for ALS, extending survival by 3-6 months. 1, 2

Monitoring Requirements for Riluzole

• Measure serum aminotransferases before initiating treatment and periodically during therapy 1
• Discontinue if baseline aminotransferases exceed 5 times the upper limit of normal 1
• Discontinue if evidence of liver dysfunction develops during treatment 1
• Advise patients to report any febrile illness due to risk of neutropenia 1

Drug Interactions to Avoid

• Strong to moderate CYP1A2 inhibitors may increase riluzole-associated adverse reactions 1
• Strong to moderate CYP1A2 inducers may decrease riluzole efficacy 1
• Avoid concurrent hepatotoxic drugs due to increased risk of hepatotoxicity 1

Palliative Care Framework

Integrate palliative care from the time of diagnosis, not at end-of-life, as this approach improves both survival and quality of life. 3, 4

Timing of Palliative Care Integration

• Begin palliative discussions at diagnosis, before communication becomes limited by disease progression 3
• Late referral to palliative services is the most common and harmful error in ALS management 3
• Early integration allows establishment of relationships with palliative care staff and addresses end-of-life planning while patients retain decision-making capacity 5, 3

Respiratory Management

Non-invasive ventilation (NIV) is the most effective intervention for prolonging survival and maintaining quality of life in ALS patients with respiratory insufficiency. 3, 6

NIV Implementation Algorithm

• Screen for respiratory symptoms: orthopnea, morning headaches, daytime somnolence 3
• Assess cognitive function before recommending NIV, as cognitive impairment significantly reduces compliance 5, 3
• Patients with mild cognitive changes are less likely to choose long-term mechanical ventilation 5
• Only 4-9% of patients choose invasive mechanical ventilation, with wide cultural variation 3

Critical Consideration

• Compliance with NIV is adversely affected by cognitive impairment, making cognitive screening essential before initiation 5

Nutritional Support

Implement nutritional interventions early when dysphagia develops, with gastrostomy placement considered before severe malnutrition occurs. 3

Dysphagia Management Strategy

• Modify food texture to ease oral and pharyngeal transport while preventing choking 3
• Teach chin-tuck posture as protection mechanism for airways to prevent laryngeal penetration 3
• Use head rotation for hypertonicity or incomplete upper esophageal sphincter closure 3
• Implement throat clearing every 3-4 swallows to prevent postswallowing aspiration 3
• Recognize that aspiration can occur without clinical signs or subjective complaints 3

Nutritional Supplementation

• Advise multiple small meals throughout the day for patients with fatigue 3
• Focus dietetic counseling on meal enrichment using high-calorie foods 3
• Add nutritional supplementation when enriched diet fails to meet requirements 3
• Add dietary fiber for constipation caused by abdominal weakness 3

Gastrostomy Considerations

• Mean feeding duration after gastrostomy is 11-18 months 3
• Placement rates vary significantly by country and healthcare system 3
• Patients with significant cognitive or behavioral deficits may show poor compliance with gastrostomy tubes 5

Cognitive and Behavioral Assessment

Screen all ALS patients for cognitive impairment at diagnosis, as up to 40% have cognitive dysfunction that significantly impacts treatment decisions and prognosis. 5, 3, 4

Impact of Cognitive Impairment

• Survival is significantly shorter in patients with frontotemporal dementia and executive dysfunction 5, 4
• Cognitive impairment increases risk of falls, choking episodes, and injuries 5
• Behavioral deficits significantly increase caregiver burden and negatively impact caregiver quality of life 5, 3
• Patients with executive dysfunction show poorer compliance with walking aids, feeding tubes, and safety devices 5

Treatment Modification Based on Cognitive Status

• Carefully consider appropriateness of NIV and feeding tube placement in patients with significant behavioral and cognitive deficits on an individual basis 5
• Apply concepts from palliative management of advanced dementias when cognitive impairment is present 5

Advance Care Planning

Initiate advance directive discussions at diagnosis, with specific trigger points including patient distress, disease evolution, or patient's expressed desire to discuss end-of-life issues. 5, 3, 4

Advance Directive Framework

• Although considered useful in 78% of European centers, only 30% of patients actually complete advance directives 3, 4
• Address preferences regarding ventilatory support, feeding tubes, and end-of-life care early in disease course 3
• Legal validity of advance directives varies by country and jurisdiction 4

Three Main Formats

• Advance declaration made by patient when still competent 4
• Advance declaration refusing specific treatments 4
• Durable power of attorney designating a representative for decision-making 4

Caregiver Support

Implement structured caregiver support from diagnosis, including counseling, support groups, and crisis management systems. 3, 4

Rationale for Early Caregiver Support

• Behavioral deficits in ALS patients have significant negative impact on caregiver quality of life 5, 3
• Caregiver burden increases considerably as disease progresses 5, 4
• Family members play a central role in management and care 7

Multidisciplinary Care Coordination

Organize care through a multidisciplinary team with clear designation of care coordinators across disease phases. 5, 3

Dutch Model of Care Coordination

• Diagnostic phase: Neurologist serves as care coordinator 3
• Rehabilitation phase: Consultant in rehabilitation medicine coordinates care 5
• Terminal phase: General practitioner becomes main care coordinator 5

Evidence for Multidisciplinary Approach

• Considerable evidence demonstrates that multidisciplinary care improves both survival and quality of life 3
• Despite international consensus, integration of palliative care varies considerably across healthcare systems 3, 4

Symptomatic Management

Sialorrhea

• Use anti-muscarinic therapy or botulinum toxin A for excessive salivation 3
• No evidence links treatment of saliva problems with improvement of dysphagia 3

Spasticity

• Muscle relaxants can be used for spasticity management 8

Speech and Communication

• Speech therapy for dysarthria as bulbar symptoms develop 8
• Implement augmentative communication devices as speech deteriorates 7

Critical Pitfalls to Avoid

• Late palliative care referral: Most common error that negatively impacts quality of life for patients and caregivers 3
• Insisting on aggressive interventions despite cognitive impairment: NIV and feeding tubes may be inappropriate in patients with significant behavioral and cognitive deficits 5
• Delayed advance care planning: Waiting until communication is severely impaired makes end-of-life discussions extremely difficult 5, 3
• Inadequate caregiver support: Failing to address caregiver burden leads to poor outcomes for both patients and families 5, 3, 4
• Assuming aspiration is clinically apparent: Both oral and pharyngeal swallowing stages may be compromised without obvious clinical signs 3

Prognosis Communication

• Mean survival is 3-5 years after symptom onset 3, 4, 9
• Only 5-10% of patients live longer than 10 years 3, 9
• Respiratory failure from respiratory muscle weakness is the most common cause of death 3
• Bulbar-onset ALS affects approximately 80% of patients with dysarthria and dysphagia 3, 9