Diagnosis of ALS

There is no one test or procedure used to diagnose ALS. Most of the tests and examinations done when ALS is suspected are just used to rule out other diseases that have the same symptoms as ALS. That is why, it is of the utmost importance that when your physician thinks you may have ALS, it is strongly recommended that you get a second opinion from an ALS expert, to solidify the first opinion.

Most of the procedures done to rule out the other diseases that have similar symptoms to ALS include:

• X-Rays (including MRIs) - this can help determine whether there is a mass or lesion that could be in the spinal area, causing weakness of arm and leg muscles. If there is a mass, it could be blocking motor signals from the actual muscles to the brain, making it difficult to move, and mimicking symptoms of ALS.
• Spinal Tap - this is a procedure in which a large needle is inserted into the lower spinal area, and CSF (or cerebrospinal fluid) is taken out. CSF is made in the brain and circulates the whole spinal cord. Getting a spinal tap can tell you whether the person has an active infection or bacteria.
• Muscle and/or Nerve Biopsy - this procedure is done to take a closer look at the actual muscle and nerve cells in your body. It helps rule out any weird or unusual cells that could be disrupting normal muscle or nerve function.
• Thorough Neurological Examination - this examination goes through a series of tests that tell you how well your nerves are functioning, and can also help the physician keep track of the progression of the disease later on, by testing the nerves and brain function again, and comparing it to these older results.
• Electrodiagnostic Tests: (includes Electromyography and Nerve Conduction Velocity). And electromyography is used to evaluate and record the electrical activity of muscles. The test basically assesses the health of muscle and nerve cells that control the muscle cells, in the body. This can help the physician keep track of the progression of the disease and get a baseline to compare later results to. As ALS is a disease specifically related to the nerve cells that control muscle cells in the body, this test is especially important in helping to rule out other diseases the symptoms could lead to. 

I've included another video that I found very helpful. She does an excellent job of explaining the progression of her symptoms of ALS. Enjoy!

Sources:
Youtube Video: "How My Initial Symptoms Progressed" By: Toochey Films

 Association, A. (2014). Epidemiology of ALS and Suspected Clusters. Retrieved from ALS Association: http://www.alsa.org/als-care/resources/publications-videos/factsheets/epidemiology.html

Pathophysiology of ALS

ALS is the most common neurodegenerative disease of motor neurons. As I've said in my previous posts, there is currently no known cause of ALS.

Disease Progression:  Most people diagnosed with ALS begin showing symptoms that involve movement of their limbs. It starts out as "clumsiness" or stumbling on their feet when they run, this progresses to "slapping gait," which is also known as foot drop. As for the arms, there is reduced dexterity and ability to do activities that involve fine detail and intricate handy work. Hands get cramped and stiff, and it eventually can affect work performance. Later, problems with the throat (which is a lot more debilitating and noticeable) progress to high risk of choking while eating, slurred speech and difficulty talking loudly. ALS patients can also have a hard time with their emotions, such as involuntary laughing or crying, and depression.

As the diseases advances, you see more ALS patients having spasticity, or involuntary tightening of their muscles, which can significantly impair the way they walk and their dexterity. Their muscles have atrophied significantly, and you can start to see it visibly. They also commonly get muscle cramps and contractures due to inability or difficulty moving their limbs.

There are many theories and studies that explore the cause of ALS. One of them suggests that excessive stimulation of glutamate receptors can cause the "excitotoxicity" that happens in ALS. Excitotoxicity is usually controlled by Sodium-dependent glutamate transporters that bind to glutamate and clear it out of the synaptic gap. The one medication that I talked about in my first post "riluzole" actually works through this pathway and gets rid of glutamate. Excitotoxicity causes the death of motor neurons in patients with ALS, and so by getting rid of glutamate (the agent that causes excitotoxicity), you can essentially slow down the progression of the disease.

As you can see in the image above, in a normal person, glutamate removal is regulated and there is not an excessive amount of it in the synaptic cleft (no excitotoxicity would be present here). In the image on the left, the person with ALS has a very excessive amount of glutamate in the synaptic cleft, and this is what causes the cell to have excitotoxicity, and cause death of a motor neuron.

Sources:

Medscape. (2014, May 2). Amyotrophic Lateral Sclerosis. Retrieved from Medscape: http://emedicine.medscape.com/article/1170097-overview

Image Source:

Youtube Video: "Amyotrophic Lateral Sclerosis"

Epidemiology of ALS

Though there is no specific cause for ALS, about 5-10% of the cases are inherited (familial ALS).  As I stated in my previous post, there are many theories on the causes, including occupational exposure, environmental exposure, chemical exposures, trauma, etc.

ALS is known to affect males more than women, especially white males. ALS becomes increasingly more common in people ages 60 or older. This means that a white male that's older than 60 years has an extremely higher risk of getting ALS than a black women in her 40's (Mehta, P).  As ALS is not a condition that is required to be reported by the U.S (Massachusetts is the only state that mandates reporting ALS), we will never know the extent of the disease in the U.S. The main goal of mandatory reporting or registering is to examine specific risk factors for ALS.

Environmental exposures that research has included as making a person of higher risk to developing ALS includes previous exposure to heavy metals (lead) and certain occupations (military service). Most of these risk factor studies use only small sample sizes and therefore have been conducted in limited geographic areas and are not clinically accurate. Other studies show that environmental toxic exposures may work against a background of increased genetic susceptibility to increase one's risk of ALS (LM, N). Evidence regarding a lot of these theories is inconsistent however, and there is still no specific cause or causes of ALS.

The incidence rate of ALS across ALL ages is estimated to be about 2 persons per 100,000 population (Mehta, P). The rate increases to five people per 100,000 population in those ages 70 or above, showing that the prevalence and risk of ALS does increase as one ages. An estimation of about 5,000 people are diagnosed with ALS every year in the U.S. Looking at ALS data across the four national databases, the prevalence rate for whites is two times more than blacks, with whites having a prevalence rate of 4.2 per 100,000 population and blacks only having a rate of 2.0 per 100,000 population. The disease has also found to be more common in non-Hispanics than Hispanics.  According to the ALS Association, some physicians are reporting that they are seeing an increasing number of younger people with ALS than in previous years (Association, A).

There are currently many epidemiological studies being conducted in the U.S., but as physicians are NOT required to report cases of ALS, it is very difficult to investigate the incidence, prevalence and risk factors of ALS.

Life expectancy of people with ALS is 2-5 years from the time of diagnosis. More than half of all patients live more than 3 years after diagnosis (Association, A).

Search Terms: "Epidemiology of ALS," Epidemiology of ALS, NIH"

Sources:

Association, A. (2014). Epidemiology of ALS and Suspected Clusters. Retrieved from ALS Association: http://www.alsa.org/als-care/resources/publications-videos/factsheets/epidemiology.html

LM, N. (1995-1996). Epidemiology of ALS. Clinical Neuroscience.

Mehta, P. (2014, June). Prevalence of Amyotrophic Lateral Sclerosis 2010-2011. Retrieved from Centers for Disease Control and Prevention: http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6307a1.htm

What is ALS?

Amyotrophic lateral sclerosis (ALS) is also referred to as "Lou Gehrig's disease."
It is a very rapidly progressing neurodegenerative disease that affects nerve cells. In simpler terms, this disease causes motor neurons (nerve cells in our body that help us move our muscles) to deteriorate and die. As motor neurons in the body degenerate, the person slowly loses control and function of their muscles, and eventually could become completely paralyzed.

Symptoms that an ALS patient may experience include muscle weakness (as their motor neurons die off), difficulty swallowing, difficulty breathing and difficulty talking. These last three symptoms are due to loss of control of muscles used in breathing (muscles in the chest and diaphragm) and also loss of control of muscles used in swallowing (walls of the pharynx, esophagus). As the disease progresses, the patient is forced to get nutrition through a feeding tube and use ventilation to help them breathe. Loss of control over skeletal muscles causes the fibers to "atrophy" or waste away, and those eventually degenerate also.

ALS is one of the most common neuromuscular diseases worldwide. Within a population of 100,000 people, there are 2 new ALS cases each year. ALS is more common in men than women, white people than black people, and can also be inherited. Being diagnosed with ALS is rare before the age of 40, but it does happen. Most people with the disease live an average of 2-5 years after their first signs of disease and only about 10% of people with ALS survive for 10 years or more.

This disease is fatal, there is no cure and no way to prevent it. Riluzole is the only FDA approved drug available to treat ALS. It slows the progression of ALS, and can only extend survival about 2-3 months.

The cause of ALS is still unknown, but there are a few theories. In the past few decades scientists have discovered that mutations in the gene that produces the SOD1 enzyme were linked with some cases of familial ALS, although it is unclear how the mutations could lead to motor neuron degeneration. Other studies look into environmental factors (exposure to toxins, physical trauma, etc.).  Recently, researchers have started focusing on RNA processing after finding that many genetic risk factors for ALS are involved in this pathway. Although the cause of ALS is still not clear, many researchers seem to agree that the development of the disease could be contributed by a number of processes.

I know you were probably expecting an "Ice Bucket Challenge" video somewhere on this post, as that has been a recent trend on social media sites. Below is my favorite "Ice Bucket Challenge" video, and in my opinion, the only one that really meant something. Fast forward to 2:00 to gain real insight into ALS.

Sources:
 Association, A. (2014). Epidemiology of ALS and Suspected Clusters. Retrieved from ALS Association: http://www.alsa.org/als-care/resources/publications-videos/factsheets/epidemiology.html