Amyotrophic lateral sclerosis

Disease Description (Causes and Symptoms)

• Definition and pathophysiology: Amyotrophic lateral sclerosis (ALS) is a progressive degenerative neurological disease that selectively affects the upper and lower motor neurons (from the cerebral motor cortex to the motor neurons of the spinal cord), causing muscle weakness, muscle atrophy, fasciculations, and spasticity. The sensory system is often preserved, but some patients may have mild sensory symptoms. Some patients may also have frontotemporal or prefrontal cognitive and behavioral impairment (frontotemporal dementia spectrum).
• Causes: Although the exact disease mechanism is unknown, genetic (familial ALS) and non-genetic factors (viruses, metabolic abnormalities, environmental exposure and heavy metals, immune abnormalities, etc.) are presumed to be involved. Known genetic variants include C9orf72, SOD1, TARDBP, and FUS.
• Main symptoms:
  • Limb muscle weakness, muscle atrophy, frequent falls, or frequently dropping objects
  • Muscle fasciculations ( fasciculations ), spasticity (spasticity)
  • Slurred speech (dysarthria), difficulty swallowing (dysphagia) — increased risk of respiratory instability and aspiration
  • Shortness of breath and nocturnal hypoventilation due to respiratory muscle weakness
  • Sensory impairment, urinary dysfunction, and cognitive decline are usually mild or uncommon
• Course and prognosis: As a progressive disease, the course varies among patients, but average survival is several years after diagnosis (generally 2–5 years), and respiratory muscle function decline is the main cause of death.

Treatment Methods

• Goals: Suppress disease progression (when possible), relieve symptoms, prevent complications, and maintain or improve quality of life
• Disease-modifying medications:
  • Riluzole: Reported to slightly extend average survival by acting on mechanisms related to neurotoxic glutamate. Liver function monitoring is required.
  • Edaravone: There is evidence that it slows the rate of functional deterioration in some patients (intravenous administration). Its indications and effects are limited, and conditions apply to its use.
• Respiratory management:
  • Noninvasive positive-pressure ventilation (NIV, e.g., CPAP/BiPAP): Improves nocturnal hypoventilation, prolongs survival, and improves quality of life
  • Mechanical ventilation and tracheostomy (end-stage options): Discussed according to the values of the patient and family
• Nutritional and swallowing management:
  • Nutritional assessment and weight monitoring
  • If swallowing difficulty is severe, consider nutritional support through gastrostomy (PEG/PRG)
• Symptomatic treatment by symptom:
  • Spasticity/cramps: Baclofen, tizanidine, etc.
  • Excessive salivation (drooling): Anticholinergic drugs, botulinum toxin injections (into the salivary glands), oral hygiene and posture management
  • Pain and discomfort: Appropriate analgesics and physical therapy
  • Depression and anxiety: Psychosocial support and medication
• Multidisciplinary care: Team-based management involving neurology, pulmonology/rehabilitation medicine, nutrition, speech therapy, physical therapy, occupational therapy, clinical dietitians, hospice and palliative care, etc., is recommended
• Genetic counseling and testing: Genetic testing and genetic counseling are recommended in cases of a family history or young-onset disease
• Precautions (complication risks and self-care considerations):
  • Report respiratory decline (difficulty breathing, nighttime sleepiness, headaches) and dysphagia (choking, weight loss) immediately
  • Pay attention to preventing complications such as aspiration pneumonia, malnutrition, pressure sores, thrombosis, and depression
  • Liver function tests (when taking riluzole) and monitoring for treatment-related adverse effects are necessary
  • Avoid excessive strenuous exercise, but appropriate exercise for maintaining muscle strength (maintenance and flexibility exercises) is recommended

Outpatient Visit Checklist (Including Example Questions)

• Items to prepare/bring:
  • A list of all medications currently being taken (including prescription drugs, antipyretic analgesics, herbal medicines, and health functional foods)
  • Copies of previous test results (EMG/nerve conduction studies, brain and spinal cord MRI, blood tests, pulmonary function tests, etc.)
  • Records of recent weight changes and food intake
  • Records of respiratory symptoms (breathing pauses during sleep, sleepiness, morning headaches), coughing strength, and whether shortness of breath is present
  • Symptoms related to swallowing difficulties (food or water getting stuck, frequency of choking)
  • Family history (similar neurological diseases, neurodegenerative diseases with young-onset, etc.)
  • Living environment (safety issues at home, presence of stairs, need for assistive devices)
• Useful information for the outpatient visit:
  • When symptoms began and the rate of progression (e.g., period from the first symptom to the present)
  • Changes in functional ability (walking distance, changes in hand function, ability to perform daily activities such as eating and changing clothes)
  • Recent history of respiratory infections or hospitalization
• Example questions to check during the outpatient visit (questions for the patient or caregiver to prepare):
  • Have you recently fallen or frequently dropped objects?
  • Have you developed slurred speech or difficulty swallowing? How often does it occur?
  • Do you become short of breath at night or extremely fatigued during the day?
  • Have any new symptoms appeared with your current medications (vomiting, jaundice, drowsiness, etc.)?

General Example Questions to Ask the Doctor

• What are the expected effects and possible adverse effects of this medication (e.g., riluzole/edaravone)? What should I do if I observe adverse effects?
• If respiratory function declines, what tests should be performed and when? What are the criteria for requiring noninvasive ventilation?
• What is the recommended timing and what are the risks of nutritional management (PEG placement)?
• How can I be connected with multidisciplinary care (rehabilitation/speech therapy/nutrition/hospice)?

Examples of Disease-Specific Questions

• Respiratory and sleep-related:
  • I have recently experienced sleep apnea or morning headaches. At what level of respiratory function test results (FVC, SNIP, etc.) do you recommend noninvasive ventilation (NIV)?
• Genetic and family-related:
  • If a family member has similar symptoms or developed the disease at a young age, do you recommend genetic testing? Which genetic tests should be prioritized?