Clinical meaning
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig disease, is a progressive neurodegenerative disease that selectively destroys upper motor neurons in the motor cortex and lower motor neurons in the brainstem and spinal cord. The degeneration of these motor neurons leads to progressive muscle weakness, atrophy, fasciculations, and ultimately respiratory failure, which is the primary cause of death.
At the cellular level, ALS involves multiple pathological mechanisms. Approximately 10% of cases are familial (genetic), with mutations in the SOD1 gene (superoxide dismutase 1) being the most studied. The SOD1 enzyme normally protects cells from oxidative damage by converting superoxide radicals to hydrogen peroxide. Mutant SOD1 gains toxic functions that damage motor neurons through protein aggregation, mitochondrial dysfunction, and glutamate excitotoxicity. In sporadic ALS (90% of cases), the exact trigger is unknown, but similar pathological processes occur.
The destruction of upper motor neurons produces spasticity, hyperreflexia, and a positive Babinski sign. The destruction of lower motor neurons produces muscle weakness, atrophy, fasciculations (visible muscle twitching), and decreased or absent reflexes. The combination of upper and lower motor neuron signs in the same patient is the hallmark diagnostic feature of ALS.
Critically, ALS spares the sensory neurons, oculomotor neurons, and the neurons controlling bowel and bladder function until very late in the disease. This means patients retain full sensation, can see and move their eyes, and maintain continence, even as they lose all voluntary muscle control. Cognitive function is preserved in most patients (though 15% develop frontotemporal dementia), meaning the person is fully aware as their body progressively fails.