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

Amyotrophic lateral sclerosis

Contents

Background

Clinical Manifestations

Management

Further Reading