Amyotrophic Lateral Sclerosis (ALS) for USMLE Step 1 & COMLEX-USA Level 1
Amyotrophic Lateral Sclerosis (ALS) for the USMLE Step 1 & COMLEX-USA Level 1 focuses on the basic science aspects, particularly neuroanatomy, neurophysiology, and molecular pathology.
Definition
ALS is a progressive neurodegenerative disorder affecting both upper and lower motor neurons, leading to muscle weakness, atrophy, and eventual paralysis.
Pathophysiology
No Sensory or Cognitive Impairment: ALS primarily affects motor neurons. Cognitive and sensory functions are typically spared (although some patients may develop frontotemporal dementia).
Pathology
Diagnosis
- Upper Motor Neuron (UMN) Degeneration: Degeneration of neurons in the motor cortex produces spasticity, hyperreflexia, and Babinski sign.
- Lower Motor Neuron (LMN) Degeneration: Loss of neurons in the anterior horn of the spinal cord and brainstem produces muscle atrophy, fasciculations, and flaccid paralysis.
- 90% of ALS cases are sporadic.
- Familial ALS: Associated with mutations in the SOD1 gene (superoxide dismutase), TARDBP (TDP-43), and C9orf72.
- Progressive, asymmetric muscle weakness (initially affecting limbs or bulbar muscles).
- UMN signs: Hyperreflexia, spasticity, and positive Babinski reflex.
- LMN signs: Muscle wasting, fasciculations, and flaccid paralysis.
- Bulbar involvement leads to dysphagia and dysarthria.
No Sensory or Cognitive Impairment: ALS primarily affects motor neurons. Cognitive and sensory functions are typically spared (although some patients may develop frontotemporal dementia).
Pathology
- Loss of anterior horn cells in the spinal cord.
- Degeneration of corticospinal tracts (upper motor neurons).
Diagnosis
- Primarily clinical.
- Electromyography (EMG) shows evidence of denervation and muscle wasting.
- Riluzole: Glutamate inhibitor that can slow disease progression.
- Edaravone: Antioxidant thought to reduce oxidative stress, providing some benefit.