Transcript What is ALS? - UNM Biology

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
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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.
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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?
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"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
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"Lateral" refers to the location of the spinal cord where portions of the nerve cells that signal
and control the muscles are located
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"Sclerosis" refers to the scarring or hardening within the nervous system as a result of nerve
degeneration
Background
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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 Hawking
Stephen 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
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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
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Inflammation of the central nervous system
Neurology Basics
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Neurons- the fundamental units of the nervous system that generate action potentials
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Action Potential- the electrical signaling generated by neurons, propagates within the nervous
system
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Lower Motor Neurons- nerve cells that send action potentials from the spinal cord to the
muscle fibers of the skeletal muscles
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Upper Motor Neurons- interneurons that connect the brain and the lower motor system in the
spinal cord
Pathophysiology
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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.
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The progressive degeneration of the motor
neurons leads to inhibition of the action
potentials reaching the muscle fibers to
promote muscle movement.
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It has been hypothesized, however, that the
motor neurons may be damaged by the
increase in glutamate
Pathophysiology (cont’d)
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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.
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Because ALS primarily involves motor neurons, sensory function is typically preserved. Few
patients complain of numbness and paresthesias.
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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
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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
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Common symptoms include:
o Weakness
o Fasciculations
o Muscular Atrophy
o Babinski Sign
o Difficulty with daily activities
o Slurred speech
o Hyperreflexia
Diagnostics
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Each patient is different and multiple tests or combination of tests may be necessary
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Tests Include:
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Electromyography (EMG)
Nerve Conduction (NCS)
Magnetic Resonance Imaging (MRI)
Blood and urine tests
Nerve biopsy
Muscle biopsy
Spinal fluid analysis
Treatment
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There is no cure yet for ALS and very few therapies.
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Treatments are often for symptoms related to ALS, such as
o Muscle pain or weakness
o Cramping of muscles
o Insomnia
o Depression
o Shortness of breath
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Long-term care may include
o Wheelchairs
o Nutritional support
o Hospice care
o Ventilators for breathing
The Challenge for Doctors
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Due to the nature of the disease, accurate diagnosis is important.
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ALS is a challenge to diagnose due to the fact that many of the observed symptoms are mimicked by
other motor neuron diseases.
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Misdiagnosis is often a result of a lack of knowledge about the disease.
Recall From Class
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Signs and symptoms for lower motor system syndrome
o Effects can be limited to a single muscle or small group of muscles
o Muscular Atrophy
o Weakness or total paralysis
o Hyperreflexia
o Hypotonia
o Fasciculations
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Signs and symptoms for the upper motor system syndrome
o Effects extent to large group of muscles
o Hypertonia
o Hyperreflexia
o Clonus (abnormal, rapid, high frequency vibrations)
o Babinski Sign
o Atrophy is rare
Differential Diagnosis
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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)
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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
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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
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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
Positive LMN
degeneration
by neurological
exam
Positive UMN
by blood work,
genetic
markers, etc.
Progressive
spread of
symptoms
YES
Does a patient
have ALS?
Neuroimaging
show other
diseases such
as MS
Positive for
pathologic
evidence of
other disease
Symptoms are
not progressing
NO
Further tests
are needed
El Escorial Criteria (cont’d)
Future Research
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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
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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
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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
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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
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ALS is a complex neurological disease. It
affects primarily the upper and lower motor
neurons that provide voluntary movements
and muscle power.
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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
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Many of the observed symptoms of ALS are
mimicked by other motor neuron diseases.
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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
Literature Cited
Cluskey, S. and Ramsden, D.B. 2001. Mechanisms of neurodegeneration in amyotrophic lateral sclerosis. J Clin: Mol Pathol. Vol 54:
386-392
Festoff, B. “Amyotrophic Lateral Sclerosis.” 2001. Encyclopedia of Life Sciences. Retrieved April 22, 2015 from
<http://personal.rhul.ac.uk/utba/011/Tutorials%20Year%202/a0000014.pdf>
Kiernan, M.C., Vucic, S., Cheah, B.C., Turner, M.R., Eisen, A.,Hardiman, O., Burrell, J.R., and Zoing, M.C. 2011. Amyotrophic
lateral sclerosis. The Lancet. Vol 377, No 9769: 942-955.
Miller, R., Gelinas, D., and O’Conner, P. (2004). American Academy of Neurology : Amyotrophic Lateral Sclerosis. New York, NY:
Demos Medical Publishing.
N.A. “ALS (Amyotrophic Lateral Sclerosis).” 2015. GlobalRPH. Retrieved April 22,2015 from <http://www.globalrph.com/als.htm>
N.A. “Amyotrophic Lateral Sclerosis (ALS).” 2013. Yale School of Medicine. Retrieved April 22, 2015 from
<https://medicine.yale.edu/neurology/patients/neuromuscular/als.aspx>
N.A. “ALS Medical Classification.” 2014. The Robert Packard Center for ALS Research at John Hopkins. Retrieved April 22, 2015 from
<http://www.alscenter.org/living_with_als/medical_classification.html>
N.A. “ALS Ice Bucket Challenge.”2015. ALS Association. Retrieved April 22, 2014 from < http://www.alsa.org/about-us/ice-bucketchallenge-faq.html>
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>
Walling, A.D. 1999. Amyotrophic Lateral Sclerosis: Lou Gehrig’s Disease. American Family Physician. Vol 15, No 59(6): 1489-1496
Oliveira, A.S.B and Pereira, R.D.B. 2009.Amyotrophic Lateral Sclerosis: Three Letters That Change People’s Life. Arq. Neuropsiiquiatt. Vol 67, No 3a: 750-782
"Stephen Hawking Quote." BrainyQuote. Xplore, n.d. Web. 21 Apr. 2015.
Wijesekera, Lokesh C., and P. N. Leigh. "Amyotrophic Lateral Sclerosis." Orphanet Journal of Rare Diseases 4.3 (2009): 1-22.
Orphanet Journal of Rare Diseases. 3 Feb. 2009. Web. 23 Apr. 2015.
Image:
"Biography." The Official Website of Lou Gehrig. N.p., n.d. Web. 21 Apr. 2015.
Video:
"Mini BIO - Stephen Hawking." YouTube. N.p., 6 Sept. 2012. Web. 21 Apr. 2015.
"What Is A.L.S. or Lou Gehrig's Disease ?" YouTube. N.p., 17 Jan. 2012. Web. 21 Apr. 2015.