Overview and Introductory Paragraph

external image lou-gehrig2.png Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is one of the most common degenerative diseases of the motor neuron system (NINDS, 2015). The disorder is named for its underlying pathophysiology with amyotrophy referring to the atrophy of muscle fibers, which are de-enervated as their corresponding anterior horn cells degenerate. Lateral sclerosis refers to the changes seen in the lateral columns of the spinal cord as upper motor neuron axons in these areas degenerate and are replaced by fibrous astrocytes (Armon, 2014).


There are two different types of ALS, Sporadic and familial. Sporadic is the most common form of the disease in the US. Sporadic ALS is a distinct syndrome characterized by a combination of upper motor neuron (UMN) and lower motor neuron (LMN) problems and occurs in about two thirds of people with ALS (NINDS, 2015). Sporadic ALS is not linked to family history or a mutated gene, but is usually seen in those people between the ages of 40-70. In about twenty-five percent of people with ALS, the initial symptoms begin in muscles innervated by the lower brainstem that control speaking, chewing, and swallowing. The disease can remain in this form for years, however, in the majority of cases ALS progresses to generalized muscle weakness throughout the body (Armon, 2014).

Quick Facts (provided by the ALS association):
  • Once ALS starts it almost always progresses, eventually taking away the ability to walk, dress, write, speak, swallow, and breathe.
  • Approximately 6,400 people in the U.S. are diagnosed with ALS each year.
  • ALS occurs throughout the world with no racial, ethnic, or socioeconomic boundaries
  • The average life expectancy of a person with ALS is two to five years from the times of diagnosis
  • Most people develop ALS between the ages of 40-75
  • The incidence of ALS is five times higher than Huntington's disease and about half that of multiple sclerosis
  • There is no cure for ALS but research efforts have increased exponentially over the last ten years.


external image 1280px-Neuron.svg.pngFunctional Anatomical Review (Structures, locations, etc.)

The human body is made up of trillions of cells. Cells within the nervous system are called neurons. These neurons are specialized cells that are designed to carry messages through electrochemical processes, known as actionpotentials. The human brain has approximately 100 billion neurons, each made up of three distinct regions (neuroscience, 2015). The dendrites are the region of the neurons that receive afferent information from other neurons. The soma or cell body of the neuron contains the nucleus and other organelles which regulate the flow of ions. The axon is the long protrusion from the cell body which has terminal ends that can innervate other neurons. Myelination along this axon causes faster transduction of the action potential. Myelination of these axons is achieved by structures known as Schwann cells (in the peripheral nervous system), and oligodendrocytes (in the central nervous system) (Williams, 2013).


There are several types of neurons, however, one of the most crucial neurons for movement is the alpha motor neuron. Alpha motor neurons are responsible for innervating skeletal muscle. At the neuromuscular junction, motor neurons release the neurotransmitter
external image synapse.jpgacetylcholine, which binds to its receptors on the muscle fiber, opening ion channels, allowing ions (sodium, potassium, and calcium) to flow in and out of the cell, which in turn creates action potentials. These motor neurons are located in the ventral horn of the spinal cord (neuroscience, 2015). Motor neurons can innervate multiple muscle fibers within a muscle but no muscle fiber is innervated individually by multiple motor neurons. This unit, which controls muscle movement, is known as the motor unit and consists of the individual motor neuron and the muscle fibers that innervate it (Knierim).


Afferent information must also travel to the brain to produce the efferent information for movement. The motor cortex is the area of the brain which is responsible for controlling various aspects of voluntary movements and is located just anterior to the central sulcus (neuroscience, 2015). The primary motor cortex, premotor cortex, and supplementary motor area, are the three regions within the motor cortex. Stimulation of the primary motor cortex requires the least amount of electrical current to elicit a movement. Stimulation of the premotor cortex or the supplementary motor area requires higher levels of electrical currents to elicit movements, and often results in more complex movements. Like the somatosensory cortex the primary motor cortex is somatotopically organized in a pattern known as “a homunculus.”
external image 1b.gif

Summary of regional function:
  • external image Human_motor_cortex.jpgPrimary motor cortex—relays motor commands to the alpha motor neurons, encodes the force of a movement, encodes the direction of movement, encodes the extent of movement, and encodes the speed of movement (Knierim)
  • Premotor cortex—signal preparation for movement, signal various sensory aspects associate with particular motor aspects, sensitive to behavioral context of a particular movement, and signals correct and incorrect actions (Sheng, 2013).
  • Supplementary motor area—responds to sequences of movement, and is involved in the transformation of kinematic to dynamic information (Knierim).


Input & Output Pathways
There are two cortical pathways that are responsible for controlling voluntary movements. With impairment due to ALS, these pathways become disrupted and movement become progressively more difficult.
external image corticospinal1320021725798.png The corticospinal tract controls motor neurons and interneurons within the spinal cord. This tract can be divided into two divisions, the medial and lateral. The line between these two sections is located at the caudal medulla where the lateral tract decussates and the medial tract remains ipsilateral. The two tracts also maintain separate functions. The medial tract is in charge of proximal musculature, while the lateral tract innervates distal musculature. Damage to this tract will result in loss of fine motor skills (Sheng, 2013).


The corticobulbar tract is responsible for control within the nuclei of the brainstem and the muscles of the head and face. This tract has influence sent to all the cranial nerves, excluding nerves VII and XII. This innervation can be described as bilateral. This is essential because unless both sides are damages, motor function can continue in a relatively normal fashion. The corticobulbar tract relays voluntary movement information to the muscles of the eyes, face, mouth, neck, and head (Knierim).

Both the lateral and the anterior corticospinal tracts begin at the cortical level in one of the three main areas of the motor cortex (primary motor cortex, supplementary motor are, or premotor cortex). Information then descends through the midbrain and the brainstem before continuing further to the spinal cord level. Along the way information traveling through both of these tracts will decussate and synapse with spinal nerves at all levels of the spinal cord. This decussation means that the left side of the body is somatotopically mapped in the right side of the brain and vice versus. (to see the two paths in greater detail refer to the image on the left.)

Diagnosis/Prognosis
There is no single test that will provide a diagnosis of ALS. However, the greatest indicator of the disease is the presence of upper and lower motor neuron signs in a single limb. Meaning, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the patient and a series of tests to rule out other diseases. This process begins by full analysis of patient history and is followed up by a neurological examination at regular intervals to assess whether symptoms such as muscle atrophy, hyperreflexia, spasticity, and muscle weakness are getting progressively worse (Armon, 2014).


In addition to symptom monitoring and history analysis, additional special tests are needed to rule out diseases which present with similar symptoms. One of these tests is electromyography (EMG), which is a special recording technique that detects electrical activity in muscles. A second common test measures nerve conduction velocity (NCV). This test can detect peripheral neuropathy or myopathy. The doctor may also order magnetic resonance imaging (MRI), a noninvasive procedure that uses a magnetic field and radio waves to take detailed images of the brain and spinal cord. Using the results from these tests and other doctors can rule out other diseases and diagnose ALS (Williams, 2013).
As the disease progresses and more of the body becomes compromised. Individuals continue to have increasing problems with moving, swallowing, and speaking or forming words. Eventually, people with ALS will not be able to stand or walk, get in or out of bed on their own, or use their hands and arms. In later stages of the disease, individual have difficulty breathing as the muscles of the respiratory system weaken. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure, usually within three to five years from the onset of symptoms. However, ten percent of those individuals with ALS survive for ten or more years (Sheng, 2013).

Treatment


No cure has been found for those who suffer from ALS. However, the drug Riluzole prolongs life for two to three months. The only downside of this drug is that it does not relieve symptoms, meaning those extended two to three months will often be painful, physically and mentally. The food and drug administration has also approved the NeuRx Diaphragm Pacing System, which uses implanted electrodes and a battery pack to cause the diaphragm to contract, to resolve some of the breathing problems. This treatment relieves symptoms and improves the quality of life for qualified patients. Finally, various drugs are available to help individuals with spasticity, pain, panic attacks, and depression. Physical therapy, occupational therapy, and rehab can also help prevent join immobility and slow down muscle atrophy (Armon, 2014).

Summary or concluding Paragraph


Amyotrophic Lateral Sclerosis, commonly known as ALS or Lou Gehrig’s disease, is progressive and degenerative neurological disorder that is inevitably fatal. The progression of this disease usually begins in one or more limbs, moves to the face/mouth, and eventually effects the person’s ability to breathe. Paralysis of the diaphragm is the lethal symptom because it prevents one from breathing without so kind of artificial support (most often a ventilator). Although there is no cure there are a few drugs on the market which either treat symptoms or prolong life. There is also the option of therapy (physical and occupational) and rehabilitation, which maintains muscle tone and calms spasticity’s.

Glossary of terms
Action Potential—a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. These potentials are elicited by ion flow across the membrane and occur in an all-or-nothing fashion.
Astrocytes—Characteristic star-shaped glial cells in the brain and spinal cord, which with there vast extensions synapse with many other neurons
Atrophy—wasting away of muscle tissue, typically due to the degeneration of cells, leading to overall weakening of the structure.
Homunculus—a cortical mapping of the human body across a cortex within the brain
Hyperreflexia—overactive or over responsive reflexes due to damage or impairment at the spinal cord above T-5
Myopathy—any disease or disorder involving a muscle this includes but is not limited to muscle spasm, cramping, stiffness, chronic fatigue.
Neuropathy—term used to describes a problem with the nerves, usually the peripheral nerves, and is characterized by a loss of sensation or a tingling feeling, most often in the feet or hands.

Listing of relevant links or suggested readings
http://www.alsa.org/news/archive/expedite-drug-development.html
http://www.alsa.org/news/archive/insights-into-gene-changes.html
http://www.ncbi.nlm.nih.gov/pubmed/26234554
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431120/

Quiz
True False/Multiple choice
1. There is a cure for ALS—True or False
2. During ALS the brain loses control of ........ leading to ...........
  • a. Muscles, depression
  • b. Muscles, pain
  • c. Movement, obesity
  • d. Muscles, paralysis
3. What does ALS actually stand for?
  • a. Atrophied lexical sensation
  • b. Atypical limb strength
  • c. Amyotrophic lateral sclerosis
  • d. Acute lactic synthesis
4. ALS is always related to family history and genes—True or False
5. How long does the typical ALS patient live after being diagnosed?
  • a. A full lifetime—ALS is not fatal
  • b. 6 months–1 year
  • c. 2-5 years
  • d. 15-20 years
6. What is the fatal factor involved in ALS?
  • a. Obesity from lack of movement/exercise
  • b. Sedative lifestyle from muscle paralysis
  • c. Depression
  • d. Trouble breathing because of diaphragm paralysis
7. What is the most common form of ALS in the USA?
  • a. Familial
  • b. Sporadic
  • c. Isolated
  • d. Both A and B
Short Answers
8. How is ALS treated? What are the benefits and downsides to each treatment?
9. List the steps a doctor would go through to diagnose ALS? Is this a single day process or must it be performed over time? Explain.
10. Is it ethically/morally/Biblically okay for a patient who is suffering from ALS to end their life via physician assisted suicide? Remember they are most likely in an advanced stage of the disease, meaning every moment of their life is filled with pain and suffering. Explain your answer and support your explanation with Biblical references.

References:
Armon, Carmel, MD. "Amyotrophic Lateral Sclerosis." : Practice Essentials, Background, Pathophysiology. Ed. Nicholas Lorenzo. MedScape, 2 May 2014. Web. 02 Dec. 2015. <http://emedicine.medscape.com/article/1170097-overview#a2>.

Knierim, James, Ph.D. "Motor Cortex (Chapter 3)." Neuroscience Online. Johns Hopkins University Deparment of Neuroscience, n.d. Web. 02 Dec. 2015. <http://neuroscience.uth.tmc.edu/s3/chapter03.html>.

"Neuroscience." - Cells of the Nervous System. Washington University, 2015. Web. 02 Dec. 2015. < https://faculty.washington.edu/chudler/cells.html>.

"NINDS Amyotrophic Lateral Sclerosis (ALS) Information Page." Amyotrophic Lateral Sclerosis (ALS) Information Page: National Institute of Neurological Disorders and Stroke (NINDS). National Institute of Health, 3 Nov. 2015. Web. 02 Dec. 2015.
<http://www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/ALS.htm#What_is_the_prognosis>.


Sheng C, Sayana P, Xiaojie Z, Weidong L. Genetics of amyotrophic lateral sclerosis: an update. Molecular Neurodegeneration [serial online]. September 2013;8(1):1-15.Accessed December 1, 2015. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766231/.


"Types of ALS." ALS Hope Foundation, 2012. Web. 2 Dec. 2015. <https://www.alshopefoundation.org/understanding-als/types-of-als.php>.

"What Is ALS?" ALSA.org. The ALS Association, 2015. Web. 02 Dec. 2015. <http://www.alsa.org/about-als/what-is-als.html>.


Williams J, Fitzhenry D, Grant L, Martyn D, Kerr D. Diagnosis pathway for patients with amyotrophic lateral sclerosis: retrospective analysis of the US Medicare longitudinal claims database. BMC Neurology [serial online]. November 2013;13(1):1-15. Accessed December 1, 2015. http://www.biomedcentral.com/1471-2377/13/160.


Quiz Answers:

1. False
2. D
3. C
4. False
5. C
6. D
7. B
8. Refer to treatment section above
9. Refer to diagnosis section above
10. Opinion question, no right or wrong answer but looking for substance and supporting details