- Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease or motor neuron disease (MND), is a progressive and fatal neurodegenerative disorder that primarily affects the motor neurons—the nerve cells responsible for controlling voluntary muscle movement. ALS leads to the gradual degeneration and death of both upper motor neurons (originating in the brain) and lower motor neurons (located in the brainstem and spinal cord), resulting in muscle weakness, atrophy, and paralysis.
- The disease usually presents in mid-to-late adulthood, most often between the ages of 40 and 70, and is more common in men than women. Although most ALS cases are sporadic, about 5–10% are familial, with inherited mutations in genes such as SOD1, C9orf72, TARDBP, and FUS. These genetic mutations can lead to toxic protein accumulation, impaired RNA metabolism, mitochondrial dysfunction, and oxidative stress—factors believed to play critical roles in the disease’s pathogenesis.
- Early symptoms of ALS are typically subtle and may vary depending on the region first affected. These may include muscle twitching (fasciculations), cramping, limb weakness, or difficulty with speech, swallowing (dysphagia), or breathing (dyspnea). As the disease progresses, patients experience increasing difficulty with motor functions such as walking, using their hands, speaking (dysarthria), and ultimately, breathing, due to the paralysis of the diaphragm and other respiratory muscles. Importantly, ALS usually does not affect sensory nerves, cognitive abilities, or autonomic functions, though some patients may develop frontotemporal dementia (FTD), particularly in those with C9orf72 mutations.
- Diagnosis of ALS is primarily clinical, based on a combination of neurological examination, electromyography (EMG), nerve conduction studies, and the exclusion of other conditions. There is no single definitive diagnostic test, though MRI and laboratory tests may be used to rule out mimicking disorders. The El Escorial criteria are often applied to support the diagnosis.
- There is currently no cure for ALS, and treatment focuses on symptom management and prolonging survival. The drug riluzole, which modulates glutamate neurotransmission, has been shown to modestly extend survival. Edaravone, an antioxidant therapy, may slow functional decline in some patients. Multidisciplinary care—including physical therapy, speech therapy, respiratory support (e.g., non-invasive ventilation), nutritional support (including gastrostomy feeding), and psychosocial counseling—is critical in optimizing quality of life.
- The prognosis of ALS is poor, with a median survival of 3–5 years from symptom onset, though some individuals may live significantly longer, especially with supportive interventions. Most patients ultimately succumb to respiratory failure. Research efforts continue to explore novel therapeutic strategies, including gene therapies, stem cell treatments, and targeted drugs that can address underlying molecular pathways.
