Amyotrophic lateral sclerosis (ALS), known as Lou Gehrig’s Disease, is a rare and severe neurodegenerative disorder. It progressively affects nerve cells in the brain and spinal cord that control voluntary muscle movement. As these nerve cells deteriorate, the brain’s ability to control muscles is lost, leading to increasing weakness and paralysis. This impacts motor function, eventually affecting movement, speech, swallowing, and breathing.
The Initial Breakdown
ALS involves the selective degeneration and death of motor neurons. These specialized nerve cells extend from the brain to the spinal cord and then to muscles throughout the body. There are two main types: upper motor neurons, located in the brain, and lower motor neurons, found in the brainstem and spinal cord. Together, they form a communication pathway, transmitting signals that enable voluntary muscle contractions. When these motor neurons are damaged, they stop sending messages to the muscles, disrupting this crucial communication.
The progressive loss of motor neurons means muscles no longer receive necessary signals. This leads to muscle weakness, a reduction in muscle size (atrophy), and involuntary muscle twitching (fasciculations). Over time, muscles may also become stiff (spasticity) due to damage to upper motor neurons. This cellular breakdown results in the loss of voluntary muscle action and paralysis.
Unraveling the Causes
Most ALS cases occur without a clear cause. Approximately 90% to 95% of ALS cases are sporadic, appearing randomly with no family history. The remaining 5% to 10% are familial ALS, inherited through genetic mutations. Familial ALS often has an earlier onset, typically in the 40s or 50s, compared to sporadic cases which commonly manifest in the 60s.
Several specific genetic mutations have been identified in both familial and some sporadic cases, including those in the C9orf72, SOD1, TARDBP, and FUS genes. These genetic changes are believed to disrupt various cellular processes, leading to motor neuron degeneration. While genetics play a role, environmental factors are also investigated, though no single definitive cause has been identified.
Environmental factors under investigation include exposure to heavy metals like lead, certain pesticides, and chemicals such as BMAA (beta-methylamino-L-alanine) found in some cyanobacteria. Smoking has also been suggested as a risk factor, particularly for women after menopause. It is generally believed that ALS results from a complex interaction between genetic predispositions and environmental influences.
First Signs of Onset
Early ALS symptoms are often subtle and vary among individuals. They typically include muscle weakness, twitching, cramps, or stiffness. These signs commonly begin in one specific body region before gradually spreading to others.
For many, symptoms first appear in the limbs, known as limb-onset ALS. This can manifest as difficulty with fine motor tasks, such as buttoning a shirt or writing, or weakness in the legs leading to stumbling and tripping. Alternatively, some individuals experience bulbar-onset ALS, where the earliest signs involve difficulties with speech or swallowing. This may present as slurred speech, a hoarse voice, or problems managing certain foods and liquids.
Who is at Risk?
Several factors increase the risk of developing ALS. Age is a primary factor, with most diagnoses occurring between 40 and 75 years. The average age of onset for sporadic ALS is typically in the late 50s to early 60s.
ALS is slightly more common in men before age 70, though this difference equalizes in older age groups. Family history is a clear risk factor for familial cases, where there is a genetic predisposition. Military service is also a factor, with veterans showing a higher risk, though specific reasons remain under investigation.