What are the key features and management options for Amyotrophic Lateral Sclerosis (ALS)?

Amyotrophic Lateral Sclerosis: Sex and Age Preponderance and Key Features

ALS demonstrates a higher incidence and prevalence in men than women, with men predominating in younger age groups and typically presenting with spinal-onset symptoms, while women more commonly experience bulbar-onset disease 1.

Epidemiological Features

• Sex distribution: ALS affects men more frequently than women in sporadic cases, though this gender difference is not observed in familial ALS 1
• Age of onset: Typically occurs in late middle age, with median survival of 2-5 years from symptom onset 2
• Prognostic factors:
  • Negative prognostic indicators include higher age at onset, bulbar onset, rapid disease progression, and weight loss >5% at diagnosis 3
  • Weight loss >5% at diagnosis doubles mortality risk (HR=1.92) 3
  • Each BMI point loss increases death risk by 24% (HR=1.24) 3

Clinical Presentation

• Motor symptoms: Progressive muscle weakness due to degeneration of upper and lower motor neurons in brain and spinal cord 4
• Presentation patterns:
  • Men: More likely to have spinal-region onset 1
  • Women: Greater tendency for bulbar-region onset 1
• Cognitive/behavioral involvement: Up to 40% of ALS patients show cognitive impairment, forming a clinical continuum with frontotemporal dementia 5, 4

Diagnostic Approach

• Diagnosis by exclusion: Requires progressive motor symptoms with both UMN and LMN signs, symptom spread, EMG compatible with LMN loss 4
• Cognitive assessment: Formal neuropsychological testing recommended despite challenges due to dysarthria and physical limitations 5
• Swallowing evaluation: Early detection of dysphagia through screening is essential 3

Management Strategies

Multidisciplinary Care

• Standard of care: Multidisciplinary clinics are associated with decreased healthcare utilization, prolonged survival, and higher quality of life 5
• Access challenges: Insurance typically covers less than half of costs for services in ALS centers 5

FDA-Approved Medications

• Riluzole: Indicated for treatment of ALS 6
• Edaravone: Indicated for treatment of ALS 7

Nutritional Management

• Monitoring: Regular screening of nutritional status, BMI, and weight every 3 months 3
• Energy requirements: Approximately 30 kcal/kg body weight for non-ventilated patients 3
• PEG placement: Should be considered when significant dysphagia develops or weight loss >10% occurs 3
• Weight goals:
  • Weight gain for BMI <25 kg/m²
  • Weight stabilization for BMI 25-35 kg/m² 3

Respiratory Care

• Monitoring: Regular assessment for signs of respiratory failure, particularly in patients with bulbar dysfunction 3
• Ventilation options:
  • Non-invasive ventilation: Improves quality and quantity of life 5
  • Medicare coverage issues: Current requirements for respiratory assist devices are outdated (FVC <50%) 5

Palliative Care

• Timing of end-of-life discussions: Should occur at specific trigger points including patient distress, disease evolution, or patient's expressed desire 5
• Advance care planning: Should begin early in disease course, documenting preferences regarding resuscitation, ventilation, nutrition, and preferred place of death 3

Future Directions

• Integrated care model: The 2024 National Academies of Sciences, Engineering, and Medicine report recommends a hub-and-spoke system of ALS care with community-based, regional, and comprehensive ALS centers 5
• Health equity: Efforts needed to address racial and ethnic disparities, as Black Americans face significantly worse health outcomes with ALS 5

Common Pitfalls

• Delayed PEG placement: Can lead to significant weight loss or critical respiratory function deterioration 3
• Cognitive impairment recognition: Failure to identify cognitive changes can lead to poor compliance with treatments and increased caregiver burden 5
• Respiratory support timing: Medicare qualification for respiratory assist devices is outdated and misaligned with current best practices 5