Amyotrophic lateral sclerosis

Background

• Degenerative disorder of the motor neurons in the brain and spinal cord

Clinical Manifestations

• Weakness, muscle atrophy, fasciculations, and spasticity
• Most commonly starts in the limbs with weakness and mobility issues (70% of patients)
• Bulbar involvement affecting swallowing and speech occurs in 25% of cases
• Can also cause cognitive and behavioural disorders from degeneration of frontal and temporal lobes of the brain (50%)
• Progresses over time, with median death from respiratory failure of 5 years after diagnosis

Management

• Care should be coordinated by a specialized ALS multidisciplinary clinic
  • Should include communication, nutrition, swallowing, mobility, activities of daily living, respiratory care, cognition, psychosocial issues, medical management and end-of-life care
• Routine screening of respiratory status at least every 3 months
  • Review symptoms, measure sitting FVC or slow vital capacity, SNIP or supine FVC or MIP, ABG or VBG or transcutaneous CO₂ (if hypercapnia is suspected), PCF measurement for cough effectiveness, and nocturnal oximetry or polysomnography if sleep-disordered breathing is suspected
• Ventilation
  • Non-invasive ventilation (NIV) improves symptoms and survival, with involvement of a respiratory specialist
    • NIV is preferred to supplemental oxygen
  • Criteria for NIV:
    • Symptoms, including orthopnea
    • SNIP ≤40 cmH₂O or MIP ≤40 cmH₂O
    • Upright FVC <65%
    • FVC sitting or supine <80% with signs or symptoms of respiratory distress
    • Abnormal nocturnal oximetry or symptomatic sleep-disordered breathing
  • If any of the criteria are met, they should start NIV within 4 weeks
• Nutritional screening and management
  • Assess weight and BMI at least every 3 months
  • Assess swallowing safety regularly
  • Management may include enteral feeding tube if risk of aspiration, decrease of 5 to 10% of weight, decrease of 1 point of BMI, BMI <18.5, or TDEE exceeding energy intake
    • When indicated, it should be inserted within 4 weeks
    • RIG may be safer than PEG, but both are reasonable
• Symptom management
  • Pain: assess and treat regularly
  • Silaorrhea
    • First-line: anticholinergic medications ± oral suction
    • Second-line: botulinum toxin as second-line therapy (after feeding tube insertion)
    • Third-line: salivary gland radiation
  • Pseudobulbar affect
    • First-line: education
    • Consider TCAs or SSRIs if indicated
    • Second-line: dextromethorphan 20 mg with quinidine 10 mg
  • Spasticity
    • Stretching
    • Medical options include baclofen, tizanidine, botulinum toxin, benzodiazepines, and cannabinoids
  • Cramps
    • First-line: tonic water, gabapentin, and baclofen
    • Second-line: quinine, levetiracetam, and mexiletine
  • Depression: psychosocial support and therapy, spiritual care, and SSRIs or SNRIs
  • Anxiety: beware benzodiazepines, which can worsen respiratory function
  • Insomnia: rule out other causes such as depression or respiratory insufficiency
  • Fatigue: investigate underlying causes, including respiratory insufficiency, sleep disorders, depression, and effect of riluzole
• Disease-modifying medications
  • Riluzole
    • Riluzole increases median survival from 11.8 to 14.8 months in RCTs
    • Registry data of riluzole suggests that its benefit is anywhere from none at all up to to 12 months extended survival
    • Generally well-tolerated, with monitoring for liver enzymes and blood counts
  • Edaravone
    • No overall benefit, but may improve outcomes in a small subset of patients: disease duration less than 2 years, FVC >80%, ALSFRS-R subcomponents all >2, and steady decline in ALSFRS-R over 3 months

Further Reading

• Canadian best practice recommendations for the management of amyotrophic lateral sclerosis. CMAJ. 2020;192(46):E1453-E1468. doi: 10.1503/cmaj.191721