ALS

(picture courtesy alsa.org) 

Starting in August 2014, the “Ice Bucket Challenge” has taken the internet by storm. The challenge is simple; once nominated, the challengers have to dump a bucket of ice water over their heads within 24 hours or donate some amount of money to the Amyotrophic Lateral Sclerosis Foundation. People have performed this challenge by themselves, with friends, even on top of mountains with a helicopter. As friends challenge friends, this #IceBucketChallenge has even reached celebrities such as  Bill Gates, Chris Pratt, the Old Spice Man, George Bush, Oprah, Justin Timberlake, and more. All this recent media revolving around the ice bucket challenge has brought in $100 million in donations for the ALS Foundation, and more importantly, spread awareness about ALS. But...what exactly is ALS?

What is ALS?

ALS stands for amyotrophic lateral sclerosis and is often referred to as Lou Gehrig’s Disease or Charcot’s disease.^1,2 It is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Motor neurons connect the brain to the spinal cord, and then the spinal cord to muscles. As these motor neurons degenerate, they can no longer send signals to the muscle fibers that normally result in muscle movement. The progressive nature of ALS eventually leads to the death of the motor neurons. As these motor neurons die, the brain loses the ability to control muscle movements. As the disease gets progressively worse, patients will eventually be totally paralyzed. Most patients with ALS will only live for 2 to 5 years.³

How many people are affected by ALS?

ALS can strike anyone, with no racial, ethnic, or socioeconomic patterns.^1,2 Usually, people between the ages of 40 to 70 are affected. ALS is slightly more common in men than women. It is estimated that 30,000 Americans may have the disease, and approximately 5,600 people in the United States are diagnosed every year. Roughly, it occurs in 1 to 3 per every 100,000 people.¹

What types of ALS are there?

There are 2 types of ALS.^1,2 Sporadic ALS (SALS) is the most common form of ALS (90% to 95% of all cases). Like the name suggests, this type of ALS can affect anyone, anywhere. Another type of ALS is known as familial ALS (FALS), which is when ALS occurs more than once in a family lineage. This type accounts for 5% to 10% of all cases. Through research, scientists have identified some common genes known to be associated with FALS, though not all. There is a third type of ALS, but this type appears in specific regions of Guam or Papua New Guinea.¹

What are the common signs and symptoms associated with ALS?

The early signs and symptoms of ALS vary depending on which motor neurons are affected.^1,2 However, the initial hallmark sign of ALS is muscle weakness. This weakness can start in the hands, arms, feet, and/or legs. Typically, muscle weakness develops on one side and it appears gradually. It can be as subtle as tripping over carpet edges. Muscle mass can decrease and muscles spontaneously twitch. Sometimes, patients with a lot of these muscle twitches or jerks complain of muscle soreness and stiffness more than weakness. The muscles can cramp as well early on in the disease, usually early in the morning. Some patients have described it as being similar to a muscle cramp while stretching in bed.

The muscles controlling swallowing, breathing, and speech can be affected as the disease spreads.^1,2 Patients can experience trouble speaking and the exaggeration of expressions of emotion, which leads to involuntary, excessive laughing or crying, called a pseudobulbar affect (PBA). As the disease progresses, more and more muscles are involved. Shortness of breath and difficulty in breathing and swallowing can be experienced by patients. Eventually, the person may have to get a ventilation machine to help with breathing. But the 5 senses of sight, touch, hearing, taste, and smell are not affected. Even in the late stages of ALS, bowel, bladder, and cognitive functions remain normal.

What are common causes or risk factors for ALS?

Because most of the ALS cases are sporadic, there are no definitive common causes or risk factors.^1,2 However, military veterans who were deployed during the Gulf War are approximately twice as likely to develop ALS. Based on an analysis of a several studies, smoking is associated with an increased risk of ALS.⁴ Formaldehyde exposure is also associated with an increased risk for ALS. But pesticide or herbicide exposure is not.

There is a genetic test available for FALS.^4­ Because this type of ALS is inherited, there are some inheritance patterns that have been identified. One such test can detect up to 35% of genetic mutations that can cause FALS.⁵

Why is early diagnosis important?

ALS is difficult to diagnose.^1,2 ALS has no cure, but there are other neurologic diseases that may look similar to ALS that can be treated, so it is important to have the correct diagnosis. If the patient does actually have ALS and the diagnosis is made early, the family can help the patient with emotional, mental, and moral support, as well as physical support as time continues. It is also important to note that because ALS is a rare disease, patients are encouraged to get a second medical opinion for diagnosis.

ALS also does not have a specific test for its identification.^1,2 To differentiate ALS from other disorders, healthcare workers call this a “diagnosis of ruling out”. A comprehensive work up is, however, required for this ruling out process; blood and urine tests, thyroid and parathyroid hormone tests, spinal tap, X-rays, magnetic resonance imaging (MRI), myelogram, muscle and/or nerve biopsy, and neurological examination. But early diagnosis is important for supportive care. Patients with FALS do have an option of getting genetic testing as mentioned above. However, treatment would not be different.

What medications are used in the treatment of ALS?

As mentioned above, ALS has no cure.^1,2,4 However, there is a drug called riluzole that can slightly increase length of survival, by about 2 to 3 months. Other medications are available to relieve any symptoms patients may experience.

Riluzole (Rilutek) does not reverse the damages already done to the neurons.^6,11 It affects both signaling pathways and signaling proteins in the central nervous system. This medication extends the time before a person needs help breathing with ventilation support. Some of the common side effects from this medication includes an increase in blood pressure, increase in heart rate, abdominal pain, diarrhea, loss of appetite, nausea, vomiting, decreased lung function, feeling weak, joint pain, dizziness, sleepiness, and vertigo. But not all of these side effects are felt by everyone, or if at all. There are some rare but serious side effects including cardiac arrest, low white blood cells or neutropenia, increased liver function tests, hepatitis, jaundice, or interstitial lung disease. Remember to always talk to a physician or pharmacist with any questions about side effects and medications.

As mentioned before, there are some medications available to help treat some of the symptoms caused by ALS, such as fatigue, muscle cramps, muscle spasms, excess saliva, pain, depression, sleep disturbances, and constipation.^1-3 The possible treatment options are summarized below.

●      Drooling: Botulinum toxin type B or low-dose radiation therapy to salivary glands can help decrease or stop drooling.

●      Excessive laughing or crying: (also known as pseudobulbar affect or involuntary emotional expression disorder) Nuedexta (dextromethorphan and quinidine) is recommended.

●      Fatigue: There are no medications currently to help with fatigue. Riluzole can actually cause fatigue in some people, so talk to your physician if you are feeling tired while taking riluzole.

●      Spasms: There is no specific recommendation, but benzodiazepines, baclofen, dantrolene, and tizanidine have been used in patients with multiple sclerosis and cerebral palsy, who also experience muscle spasms.

●      Cramps: Similar to spasms, there are no specific recommendations, but there are treatments that can be tried. Gabapentin, vitamin E, and riluzole have been used for this indication, however, studies that did look that these medications show that they may not help everyone.

●      Depression: There are no recommendations on a specific medication, but there are many effective treatments available.

●      Insomnia: Just like depression, there are no specific recommendations, but there are also many treatment options.

Earlier on in the disease state, there are some rehabilitative options to assist ALS patients.¹ Foot-drop splints can help prevent someone from tripping. Finger extension slips can help someone get a better hand grip on items. Diet and nutritional support is especially important for patients with ALS as they develop problems with swallowing and choking. For difficulty swallowing, a feeding tube may help restore normal nutrition. For those patients whose disease states have progressed to respiratory failure, mechanical ventilation can be an option.

What can I do to prevent ALS?

There is currently no way to prevent ALS. However, research towards ALS certainly helps. Scientists can continue to research more effective treatments and genetic testing to help better the lives of those who have been affected by ALS.

Where can I find more information on ALS?

●      ALS Association
http://www.alsa.org/

●      ALS Therapy Development Institute
http://www.als.net/

●      GeneTests: Genetic Testing Available and Near You
https://www.genetests.org/search/disorders.php?search=Amyotrophic%2520Lateral%2520Sclerosis&submit=Search&start=0

●      KidsHealth: Lou Gehrig’s Disease For Kids
http://kidshealth.org/kid/grownup/conditions/als.html

●      Muscular Dystrophy Association, ALS Division Fact Sheet http://static.mda.org/publications/PDF/FA-ALS.pdf

●      National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/ALS.htm

●      ALS Association Facts Sheet - Spanish
http://www.alsa.org/en-espanol/qu-es-la-ela.html?print=t

Written by:

Yijia Luo, PharmD Candidate, 2015

UIC College of Pharmacy

References

1.     Brown RH Jr. Amyotrophic lateral sclerosis and other motor neuron diseases. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012. http://accesspharmacy.mhmedical.com/content.aspx?bookid=331&Sectionid=40727190. Accessed August 28, 2014.

2.     Standaert DG, Roberson ED. Treatment of central nervous system degenerative disorders. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e. New York, NY: McGraw-Hill; 2011. http://accesspharmacy.mhmedical.com/content.aspx?bookid=374&Sectionid=41266228. Accessed August 28, 2014.

3.     Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73(15):1227-1233. doi:10.1212/WNL.0b013e3181bc01a4.

4.     Dynamed [online database]. Ipswich, MA: EBSCOHost; 2014. http://search.ebscohost.com/login.aspx?direct=true&db=dme&AN=116744&site=dynamed-live&scope=site. Updated June 25, 2014. Accessed September 2, 2014.

5.     ALS DNA Tests Available. Muscular Dystrophy Association website. http://mda.org/alsn/als-dna-tests-available. Accessed September 17, 2014.

6.     Rilutek [package insert]. Bridgewater, NJ: Sanofi-Aventis; 2012.