Amyotrophic Lateral Sclerosis (ALS)

Presented by Alexia DeLara, Vanesa Mesic, Joseph Ekofo,

Amber Tinagero, and Jerilyn Curtis

What is ALS?ALS is a rapidly progressive idiopathic neurodegenerative disease primarily targeting

voluntary motor neurons, which may result in muscle weakness, paralysis, and respiratory failure

Introduction● Why we chose ALS?

We chose to do our presentation on ALS because it is a very rare condition with devastating effects. We wanted to increase awareness about this disease and present some of the research that are being conducted on this topic.

● In this presentation, you will find information about ALS including some background information, famous cases, causes, the pathophysiology behind the disease, symptoms, diagnosis, treatment, challenges that doctors face, differential diagnosis, future research, and the ice bucket challenge.

What is in the name?● "Amyotrophic" derives from Greek

"A" means no or negative; "Myo" refers to muscle; "Trophic" means nourishment Amyotrophic literally means “No muscle nourishment"

○ When a muscle has no nourishment, it "atrophies" or wastes away

● "Lateral" refers to the location of the spinal cord where portions of the nerve cells that signal and control the muscles are located

● "Sclerosis" refers to the scarring or hardening within the nervous system as a result of nerve degeneration

Background● 1825-1893 Jean-Marie Charcot, a french neurologist, reported the first characteristics of ALS ● 1874 Amyotrophic Lateral Sclerosis was named ● In the US, approximately 5,000 people are diagnosed yearly with ALS● Most are between the ages of 45-65● Presently in the United States, about 30,000 people are victims of ALS ● Most will die within 3-5 years of contracting the fatal syndrome● 10% of all known cases are hereditary● Males are more susceptible to ALS● The condition has no racial or ethnic boundaries. ● Doctors Scarmeas, Shih, Stern, Ottoman, and Rowland recently published a scientific article concluding

that subjects with motor neuron diseases were more likely to be slim, or had once been serious athletes

Lou Gehrig

Henry Louis Gehrig was born on June 19, 1903. He was a famous New York Yankee’s baseball player who was well known for setting various records. He began to show signs of the disease in 1938. In 1939, doctors at the Mayo Clinic diagnosed Gehrig with ALS. On May 2, 1939, Gehrig voluntarily removed himself from the game; shortly thereafter, he retired from baseball. He passed away on June 2, 1941. The diagnosis of his disease brought awareness to the condition and after his death, the disease became known as Lou Gehrig’s Disease.

Stephen HawkingStephen Hawking was born on January 8, 1942. He was diagnosed with ALS at age 21 while still attending college. Despite his physical limitations, he has made great strides in the field of cosmology and physics. In spite of being wheelchair bound and dependent on a computerised voice system for communication, he continues to combine family life with his research in theoretical physics and an extensive program of travel and public lectures. Upon diagnosis, he was given 2 years to live. Mr. Hawking is now 73 years old, surpassing the life expectancy of his illness decades over.

In 2014, the movie "Theory of Everything" portrays Stephen Hawking's life with ALS.

Possible Causes● The specific cause of ALS is unclear but researchers believe there

are several factors that contribute to the condition:1. Genetic Factors

❏ Researchers have found 2 genes associated with the disease: ALS1 and ASL2. ALS1 was discovered in 1993, found on chromosome 21

2. Mutation of the Superoxide dismutase enzyme (SOD1)

❏ which normally rid the body of free radicals produced in cell metabolism

3. Excitotoxicity due to increase levels of Glutamate

4. Inflammation of the central nervous system

Neurology Basics● Neurons- the fundamental units of the nervous system that generate action

potentials

● Action Potential- the electrical signaling generated by neurons, propagates within the nervous system

● Lower Motor Neurons- nerve cells that send action potentials from the spinal cord to the muscle fibers of the skeletal muscles

● Upper Motor Neurons- interneurons that connect the brain and the lower motor system in the spinal cord

Pathophysiology● The exact mechanism of ALS remains

unclear due to the uncertainty of causation but it has been determined that it affects the upper and lower motor neurons that provide voluntary movements and muscle power.

● The progressive degeneration of the motor neurons leads to inhibition of the action potentials reaching the muscle fibers to promote muscle movement.

● It has been hypothesized, however, that the motor neurons may be damaged by the increase in glutamate

Pathophysiology (cont’d)● The cardiac and smooth muscle of the digestive system are regulated involuntary via the autonomic

nervous system. Therefore, the heart and the digestive system are not affected by ALS.

● Because ALS primarily involves motor neurons, sensory function is typically preserved. Few patients complain of numbness and paresthesias.

● Skin integrity is usually maintained, primarily due to the combination of preserved sensory function and continued control of bowel and bladder function. o Some studies on patients with ALS have shown morphologic changes in the skin that are

complex and poorly understood but believed to help preserve the skin integrity.

Symptoms● Early symptoms of ALS may be subtle and often overlooked. Symptoms vary for

each patient and proper diagnosis is critical in order to have early treatment interventions

● Common symptoms include:o Weaknesso Fasciculations o Muscular Atrophyo Babinski Signo Difficulty with daily activitieso Slurred speecho Hyperreflexia

Diagnostics ● Each patient is different and multiple tests or combination of tests may be

necessary

● Tests Include:

o Electromyography (EMG)o Nerve Conduction (NCS) o Magnetic Resonance Imaging (MRI) o Blood and urine testso Nerve biopsyo Muscle biopsyo Spinal fluid analysis

Treatment● There is no cure yet for ALS and very few therapies.

● Treatments are often for symptoms related to ALS, such aso Muscle pain or weaknesso Cramping of muscleso Insomniao Depressiono Shortness of breath

● Long-term care may includeo Wheelchairso Nutritional supporto Hospice careo Ventilators for breathing

The Challenge for Doctors● Due to the nature of the disease, accurate diagnosis is important.

● ALS is a challenge to diagnose due to the fact that many of the observed symptoms are mimicked by other motor neuron diseases.

● Misdiagnosis is often a result of a lack of knowledge about the disease.

Recall From Class● Signs and symptoms for lower motor system syndrome

o Effects can be limited to a single muscle or small group of muscleso Muscular Atrophyo Weakness or total paralysiso Hyperreflexia o Hypotoniao Fasciculations

● Signs and symptoms for the upper motor system syndromeo Effects extent to large group of muscleso Hypertoniao Hyperreflexia o Clonus (abnormal, rapid, high frequency vibrations)o Babinski Signo Atrophy is rare

Differential Diagnosis● ALS has multiple forms depending on what physical processes are affected.

o Classical ALS Upper and lower motor neuron deterioration (presented in this

presentation) Majority of those diagnosed have this form of ALS

o Primary Lateral Sclerosis (PLS) Upper motor neuron deterioration Lower motor neuron deterioration may or may not occur Rarest form of ALS

o Progressive Bulbar Palsy (PBP) Lower motor neuron deterioration Affects approximately 25% of those diagnosed

o Progressive Muscular Atrophy (PMA) Lower motor neuron deterioration Upper motor neuron deterioration may or may not occur

o Familial Heritable genetic mutation

Differential Diagnosis (cont’d)● Motor neuron diseases that are extremely related to ALS include:

1. Primary Lateral Sclerosis (PLS)

a. Distinguished from ALS by the presence of primarily lower motor neuron signs and symptoms and the presence of abnormal nerve conduction

2. Multifocal Motor Neuropathy

a. Distinguished from ALS by death of neurons only in anterior horn cells of the lower motor neurons , shows only lower motor signs and symptoms

3. Adult Spinal Muscular Atrophy

a. Distinguished from ALS by death of neurons only in anterior horn cells of the lower motor neurons and only shows lower motor signs and symptoms

4. Progressive Bulbar Atrophy

a. Distinguished from ALS by remaining isolated within the bulbar muscles.

Analyzing Differential Diagnosis

● The El Escorial criteria outlines the requirements for diagnosis o This criteria offers doctors diagnostic tests and guidelines for choosing the

right diagnosis of ALS

● Doctors look at both lower motor neuron(LMN) and upper motor neuron(UMN) diagnostics

Lower Motor Neuron Upper Motor Neuron

Pseudobulbar features Clonus

Muscular Atrophy Babinski Sign

Weakness Hoffman Response

Fasciculations Hyperactive reflexes

El Escorial Criteria

Does a patient have ALS?

Positive UMN by blood work, genetic markers, etc.

Neuroimaging show other diseases such as MS

Progressive spread of symptoms

Positive for pathologic evidence of other disease

YES

Symptoms are not progressing

NO

Further tests are needed

Positive LMN degeneration by neurological exam

El Escorial Criteria (cont’d)

Future Research● One of the research topics that many scientists focus on is determining what makes

motor neurons extremely vulnerable and determining how the disease spreads from neuron to neuron. o Currently being conducted by Sami Barmada, MD, PhD: University of Michigan

● Another research topic being focused on is the mutation of SOD-1 and determining if it plays a role in the pathogenesis of the disease.o Researchers try to determine if this protein propagates to the central nervous

system when high concentrations are ectopically placed o Currently being conducted by David Borchelt, PhD: University of Florida

● Recently, research was conducted by injecting induced pluripotent cells (cells that were undifferentiated from adult cells) into the spinal cord of a rat with ALS. o Results showed the iPS cells implanted in the spinal cord, survived and and

began to differentiate into neuronal cells.

Ice Bucket Challenge● The ice bucket challenge is a fundraising campaign to bring awareness to ALS

○ The Challenge went viral on social media in the summer of 2014● The challenge entails being nominated to participate, pouring ice water on

one’s self and nominating others to participate. ○ While the challenge is being carried out it is recorded and posted online

with the hashtag #icebucketchallenge● Originally, participants were nominated and had to complete the challenge

within 24 hours or they were given the option to donate to the ALS Association but many people participated in both.

● The ice bucket challenge has also been used to bring awareness for various causes but it are those who have been impacted by this disease that start the challenge

● As of today, the ALS Association has raised approximately $115 million since July 2014 to be used toward research and treatment care

● For more information, please visit http://www.alsa.org/fight-als/ice-bucket-challenge.html

Our Challenge

#icebucketchallenge

Now...

Conclusion● ALS is a complex neurological disease. It

affects primarily the upper and lower motor neurons that provide voluntary movements and muscle power.

● The exact mechanism of ALS remains unclear but researchers believe there are several factors that contribute to the condition including, but not limited to, genetic and inflammation of the central nervous system

● Many of the observed symptoms of ALS are mimicked by other motor neuron diseases.

● There is no cure for ALS yet. However, there are several research studies that are currently in progress, exploiting alternative methods of treatment.

"My advice to other disabled people would be, concentrate on things your

disability doesn't prevent you doing well, and don't regret the things it interferes

with. Don't be disabled in spirit as well as physically."

-Stephen Hawking

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Literature Cited (cont’d)N.A. “New study shows stem cells promise as future ALS treatment.” 2015. Stem Cells Translational Medicine. Retrieved on April 23, 2015 from <http://stemcellstm.alphamedpress.org/site/misc/PressRelease020.xhtml>

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"Stephen Hawking Quote." BrainyQuote. Xplore, n.d. Web. 21 Apr. 2015.

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