What is amyotrophic lateral sclerosis?
Amyotrophic lateral sclerosis (ALS) is a rare neurological disorder that affects motor neurons, which are nerve cells that control voluntary muscle movement such as walking, talking and eating. As ALS is a progressive disease, the symptoms worsen as time goes on. At this moment, there is no cure for ALS as well as no successful treatments that can help stop or reverse disease progression.
How motor neurons communicate?
Motor neurons start in the brain and extend out to the spinal cord, as well as to muscles throughout the body. Motor neurons create a network that allows the brain to communicate with voluntary muscles and signals them to move. In this manner, communication that originates from motor neurons in the brain (known as upper motor neurons) are conveyed to motor neurons in the spinal cord and to a region called the motor nuclei of the brain (known as lower motor neurons). Then, the communication continues from the spinal cord and motor nuclei to a specific muscle or group of muscles.
Patients with ALS develop deterioration of the upper and lower motor neurons, causing the neurons to eventually die and halt communication to the muscles. Once these muscles are no longer in use, they start to twitch and eventually lose their functionality and waste away. Ultimately, the brain of ALS patients is no longer able to either commence or control voluntary muscle movements.
The initial symptoms of ALS generally involve muscle weakness or stiffness. Eventually, all muscles that a patient has voluntary control over become affected. Ultimately, patients lose their strength and can no longer walk, talk, eat, and even breathe. Most ALS patients die from the inability to breathe (known as respiratory failure). This generally occurs between 3 to 5 years from when the patient’s symptoms manifest. However, approximately 10 percent of ALS patients go on to live for 10 years or more.
What are the different types of ALS?
There are two different types of ALS, sporadic and familial.
Most patients with ALS (approximately 90-95 percent) are thought to be sporadic cases. As there is no familial component to sporadic ALS, it can develop in anyone at random. There are no clearly associated risk factors with sporadic ALS. Studies have shown that family members of sporadic ALS patients are at a higher risk of developing the disease. However, the risk overall is quite low and most family members will not develop ALS.
Familial (genetic) ALS
In approximately 5-10 percent of cases, ALS is genetic or familial, meaning that a patient inherits a disease-causing mutation from their parents. This type of ALS can be caused if even only one parent has a disease-causing mutation in their gene.
Scientists have discovered mutations in more than a dozen genes that can result in the development of familial ALS. The most common mutation, present in approximately 25-40 percent of patients, that causes ALS is in a gene called C9ORF72. Mutations in this gene have also been implicated in ALS-FTD (fronto-temporal dementia), a disease in which patients develop both motor neuron and dementia symptoms. Another common mutation, which occurs in 12-20 percent of familial ALS cases, resides in a gene called SOD1, which provides the cell instructions to make an enzyme called copper-zinc superoxide dismutase 1.
- The majority of patients with ALS will develop the disease between 40 and 70 years of age, though it can also develop in younger patients.
- ALS most commonly occurs in individuals that are over 60 years of age.
- In the United States alone, there are approximately 30,000 people living with the disease, with 5,000 new patients diagnosed annually.
- Study estimates indicate that ALS could be the cause of death for as many as 5 in 100,000 people that are 20 years or older.
- The incidence of ALS is similar to that of multiple sclerosis but five times more than that of Huntington’s disease.
What is the ALS prognosis?
Generally, the outlook for ALS is poor as most patients die from the disease. Statistics indicate that:
- 50% of patients live at least three or more years post-diagnosis,
- 25% of patients live for 5 years or more and
- up to 10% live more than 10 years.
Once the disease manifests, the physical condition of patients usually starts to deteriorate. At first, patients have issues with conducting everyday tasks due to muscle weakness and stiffness. Some patients will go through small periods, which can range from weeks to months, without further loss of functioning ability. Some might even recover some function. However, this improvement only lasts a year or more in less than 1% of patients.
The time scale in which a patient experiences worsening symptoms is variable and depends on the patient
One of the factors that lead to this variability includes the type of disease. For example, patients that experience the bulbar onset of ALS (in which patients initially experience muscle weakness in the head and neck) have a worse prognosis compared to those that have a spinal onset (which initially affects limbs and trunk). Furthermore, patients that experience respiratory onset ALS (which initially affects the respiratory system) have a particularly poor prognosis.
Another factor that affects prognosis is the age at which the patient develops the disease. In fact, patients that develop the disease later in life have a worse prognosis and patients that develop ALS before they are 40 are known to survive longer.
The type of ALS can also affect prognosis. In fact, studies have shown that patients with familial ALS, as those with A4V mutation in the SOD1 gene, are likely to only survive 12 months. On the other hand, other mutations can lead to a less aggressive disease course and longer survival.
Finally, there is some controversy in the field whether three other factors play a role in prognosis. These three factors include gender, time to diagnosis (the time it takes for a patient that is experiencing symptoms to become diagnosed), and whether ALS manifests in the upper or lower limbs.