Amyotrophic Lateral Sclerosis (ALS)
ALS is a progressive neurodegenerative disorder characterized by degeneration of upper and lower motor neurons in the brain and spinal cord, resulting in progressive muscle weakness, atrophy, and eventual respiratory failure with a median survival of 3-5 years after symptom onset. 1
Clinical Presentation
ALS presents in two main forms:
Bulbar onset (25-35% of patients):
- Affects speech and swallowing first
- Almost 80% develop dysarthria and dysphagia
- Associated with shorter life expectancy 1
Spinal/limb onset (65-75% of patients):
- Begins with muscle weakness in limbs
- Typically presents with asymmetric weakness 2
Key Clinical Features
- Upper motor neuron signs: Hypertonicity, hyperreflexia, spasticity
- Lower motor neuron signs: Muscle fasciculations, weakness, atrophy
- Preserved functions: Sensory, autonomic, and oculomotor neurons 1, 3
- Cognitive dysfunction: Present in 20-50% of cases, primarily frontotemporal dementia 1
Epidemiology
- Annual incidence: 1-2 per 100,000 population
- Majority of cases (85-90%) are sporadic
- 10-15% are familial with autosomal dominant inheritance pattern
- Median survival: 3-5 years, with 5-10% living longer than 10 years 1, 2
Etiology and Pathogenesis
The etiology of ALS is multifactorial, with several mechanisms implicated:
- Increased oxidative stress
- Glutamate excitotoxicity
- Mitochondrial dysfunction
- Inflammation
- Apoptosis 1, 3
Genetic Factors
- More than 20 genes have been associated with ALS
- Most common genetic cause: Hexanucleotide repeat expansion in C9orf72 gene (30-50% of familial ALS, 7% of sporadic ALS)
- About 20% of familial ALS cases are associated with mutations in the copper/zinc superoxide dismutase-1 (SOD1) gene 3, 2
Diagnosis
Diagnosis is primarily clinical, supported by electrophysiological studies and exclusion of other conditions:
- Electromyography (EMG) and nerve conduction studies (NCS): Key diagnostic tools 4
- MRI of brain and spinal cord: Primarily to exclude other conditions rather than confirm ALS 1
- MRI head without IV contrast is the recommended imaging modality
- Common MRI findings: Abnormal T2/FLAIR signal in corticospinal tracts, "snake eyes" appearance in anterior horns of spinal cord 1
Nutritional Considerations
Malnutrition is common in ALS due to:
- Bulbar dysfunction causing difficulty chewing and swallowing
- Anorexia related to psychosocial distress and depression
- Weakness of abdominal and pelvic muscles causing constipation
- Potentially increased energy requirements from respiratory effort 1
Management Approach
Disease-Modifying Treatment
- Riluzole: Only disease-specific treatment with neuroprotective effects through glutamate inhibition 3
Supportive Care
- Multidisciplinary approach: Essential for optimal management
- Palliative care: Should be integrated from diagnosis, not just at end-of-life 1
- Nutritional support: Regular assessment of BMI and weight loss to detect early malnutrition 1
- Respiratory support: Non-invasive ventilation when indicated
- Physical therapy: Appropriate exercise may help maintain function and prevent disuse atrophy 5
Prognosis and End-of-Life Care
- Primary causes of death: Respiratory failure and malnutrition with dehydration
- Negative prognostic factors: Bulbar onset, older age, rapid weight loss
- Weight loss impact: 5% weight loss at diagnosis associated with doubled risk of death 1
Common Pitfalls in Management
- Late referral to palliative care: Should be initiated at diagnosis, not just terminal phase
- Inadequate nutritional monitoring: Regular assessment of BMI and weight loss is essential
- Overlooking cognitive/behavioral symptoms: Up to 50% have some cognitive changes
- Insufficient communication: Effective coordination between multidisciplinary ALS team, primary care, and palliative care is critical
- Inappropriate imaging: CT has limited value compared to MRI for diagnosis
ALS is a devastating disease requiring comprehensive care focused on maintaining quality of life. Early integration of palliative approaches, proactive nutritional management, and coordinated multidisciplinary care are essential to optimize outcomes for patients with this progressive condition.