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Amyotrophic Lateral Sclerosis (ALS) – A Progressive Neurodegenerative Disorder

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a devastating and progressive neurodegenerative disorder that affects the nerve cells in the brain and spinal cord. It is characterized by the gradual degeneration and death of motor neurons, which are responsible for controlling voluntary muscle movements. This progressive loss of motor neurons leads to muscle weakness, atrophy, and ultimately paralysis, severely impacting a person’s ability to speak, eat, move, and breathe.

Pathophysiology of ALS:

ALS is marked by the selective and progressive loss of both upper motor neurons (neurons located in the brain that send messages to the spinal cord) and lower motor neurons (neurons in the spinal cord that send messages to the muscles). The exact cause of this neuron degeneration remains largely unknown, although several mechanisms have been proposed, including glutamate toxicity, oxidative stress, mitochondrial dysfunction, and protein misfolding.
Glutamate is an important neurotransmitter involved in normal brain function. However, in ALS patients, excessive levels of glutamate can lead to excitotoxicity, where overstimulation of receptors causes neuron damage and death. Additionally, oxidative stress from free radicals damages cell components, further contributing to neuron degeneration. Mitochondria, the cell’s powerhouse, are also affected, leading to energy deficits and cell death. Abnormalities in protein processing can result in the accumulation of misfolded proteins, which can disrupt cell function and lead to neurodegeneration.

Causes and Risk Factors:

While the exact cause of ALS remains unclear, both genetic and environmental factors are believed to play a role. Approximately 10% of ALS cases are familial, meaning they are inherited through genetic mutations. The most common genetic mutations associated with familial ALS occur in the SOD1, TARDBP, FUS, and C9orf72 genes. These mutations can lead to the production of abnormal proteins that damage motor neurons.
In sporadic ALS, which accounts for the remaining 90% of cases, no specific family history or genetic cause can be identified. Environmental risk factors are being investigated, including exposure to toxins, smoking, military service, and physical trauma. However, no definitive environmental triggers have been conclusively linked to ALS.

Symptoms and Progression:

The onset of ALS symptoms is usually subtle and can vary from person to person. Early symptoms may include muscle weakness, twitching, and cramping, often starting in one limb and gradually spreading to other parts of the body. As the disease progresses, patients experience increasing difficulty with tasks that require fine motor skills, such as buttoning a shirt or writing.

Muscle weakness progresses to more severe atrophy and paralysis. Speech becomes slurred and difficult, and patients may eventually lose the ability to speak altogether. Swallowing difficulties, known as dysphagia, can lead to choking and aspiration pneumonia. Breathing problems arise as the muscles that control respiration weakens, ultimately requiring ventilatory support. Despite the loss of voluntary muscle control, sensory neurons and cognitive functions typically remain intact, leaving patients fully aware of their decline.