Introduction
Motor neuron diseases or MND are a group of “progressive neurological disorders involving the destruction of motor neurons in the nerve cells” (Kunci: p. 70) responsible for transmitting impulses that instruct the upper and lower body to move. Other voluntary muscle movements that are inhibited include speaking, walking, breathing, and swallowing. Motor neuron diseases have varied differences but they all have detrimental to the health of the patient. On most occasions, motor neuron diseases are acquired but in 5-10% of the cases, the disease is hereditary. Examples of classified motor neuron diseases are Amyotrophic Lateral Sclerosis (ALS) or more commonly referred to Lou Gehrig’s disease in the United States (After the baseball player who was diagnosed with the disease), spinal muscular atrophy, poliomyelitis, and primary lateral sclerosis are the more common ones. (Kunci: p. 70).
Prevalence Levels
All these diseases have unique differences as to their origin and causative agents but their later effect on the patient is similar. Motor neuron diseases affect all categories of people ranging from children to adults. The disease does however have a much higher likelihood of occurrence in men than in women. For the case of children especially in “inherited or familial forms of the disease” (Oliver: p. 126) symptoms of the disease can be present at birth or exhibit themselves just before the child learns how to walk. The prevalence rate for the disease is approximately 1-5 out of a possible 100,000 people. “About 5,600 cases are diagnosed in the U.S every year.” (Miller et al: p. 53) There are three known “hotspots” for MND in the world. These are the Kii peninsula of Japan, amongst tribal populations in Papua New Guinea and the Chamorro inhabitants from the Guam Pacific.
Symptoms for the disease present themselves mostly as one grows older and especially in the 50-70 age bracket. The peak age for the onset of the symptoms is 55 years. Cases younger than the age of 50 have been reported and are usually referred to as “young-onset MND”. After the age of 85, the risk factor for the disease somehow starts declining. Certain environmental factors have been identified as the most likely to cause the disease. These are prolonged radiation exposure, exposure to a severe electrical shock that can lead to a coma and certain neurotoxins contained in cycad nut flour, and exposure to bats that have eaten cycad nuts. Some soldiers who served in the 1st Gulf War also exhibited MND-like symptoms and this was attributed to exposure from depleted uranium that was used in making ammunition. The condition was referred to as Gulf war syndrome though the findings were never widely accepted, and more research was required. Another less probable cause like playing soccer has been mentioned. (Miller et al: p. 54).
Biological Mechanism
To understand how the disease affects the body, a brief introduction to the structure and functions of motor neurons in the body would be necessary. “A motor neuron is one of the largest cells in the human body”.(Kunci: p. 75) It is made up of a large cell body that contains a large number of appendages spreading out in every direction (360 degrees) from the cell body. The appendages are called dendrites and can receive instructions from adjacent neurons via a chemical process. The dendrites communicate with other neurons when a unique protein channel on its surface is stimulated via an impulse by a neurotransmitter referred to as acetylcholine. Extending from the cell body of the motor neuron is a portion called the axon. With suitable conditions, an electrical signal goes through the axon’s length to an area termed the axon terminals. “The terminals are extended in all directions and have at their tips a region identified as the synaptic end bulb” (Kunci: p. 75). The synaptic end bulb releases acetylcholine which crosses a small gap to reach a protein in another dendrite. This process replicates itself at every axon terminal whereby nerve impulses are transmitted from dendrite to dendrite through stimulation of the protein channels.
This is how information is communicated throughout the human body; from reflex actions like blinking to quickly pulling your hand after touching a hot surface. The motor neurons are stacked up in a band which in some ways makes it possible for electrical signals to be sent to the respective muscles from the brain. The nerve tracts are unique in their numbers and functionalities and extend all over the body’s muscles thereby helping them contract and relax via the brain which transmits the impulses (Kunci: p. 76). The performance of the motor neuron is greatly hampered when it is damaged either through disease or injury. The muscles of the body are subsequently affected. In most cases “a disorder of the motor neurons results in progressive muscle atrophy” (Kunci: p. 76) or shrinking and wasting of the muscles This condition mostly affects some of the muscles in the body; it’s only in rare and extreme conditions that all the muscles would be affected. “Muscle twitching (fasciculation) is common among these disorders” (Kunci: p. 76).
Due to the complexity of the nervous system, motor neuron diseases are difficult to diagnose early and treat. The early symptoms are usually weakening of the general body movements that could lead to total incapacitation. The prognosis in some cases is fatal. The majority of motor neuron diseases are classified according to their disorders. We will look at each of the MND mentioned above and their effects on various parts of the body plus the symptoms they exhibit.
Types of Progressive Neurological Disorders
Amyotrophic Lateral Sclerosis or Lou Gehrig’s disease is a disorder that advances slowly but eventually leads to death and interferes or disrupts signals to all body muscles. It affects both the upper and lower motor neurons. In about 75% of the cases, patients with this disorder also develop further weakening and wasting of the bulbar muscles. (Muscles in the mouth, throat, and face region that control speech swallowing and chewing) Early-onset of symptoms becomes visible on the arms and hands, legs, or difficulty in swallowing due to weakening of muscles. Atrophy occurs unevenly on both sides of the body. Eventually, patients lose all bodily movements, and the strength of the various body limbs like the legs, arms, etc wanes. Spasticity, fasciculation, exaggerated reflexes, and inability to form certain words due to slurred speech are some of the symptoms that are exhibited. (Wade: p. 62)
At the latter stages of the disease, muscles of the diaphragm and chest are unable to function properly and the patient loses the ability to breathe hence requiring an aspirator. Somehow, a patient’s mind and personality remain intact even in the later stages of the disease. The age groups most likely to be affected by ALS are the 40-60 years bracket but younger and older people have also been affected by the disease. Men are still more likely to be affected than women and most of the reported cases occur spontaneously with little indication of the causative agents; even amongst family members of the patients. However, a familial form of ALS in adults has been identified and its roots can be traced to the mutation of the SODI gene located on chromosome 21. It is still a drop in the ocean when it comes to understanding the disease and finding its cure but it is a step in the right direction. The major cause of death in ALS is respiratory failure usually within 3-5 years from the beginning of the symptoms. 10% of patients survive for at least 10 or more years. (Wade: p. 66)
Spinal muscular atrophy or SMA is an inherited disorder affecting the lower motor neurons. “Continued degeneration of the anterior horn cells of the spinal cord results in weakening and wasting of the skeletal muscles”.(Silver: p. 235) The weakness is more severe in the legs as compared to the arms. Spinal muscular atrophy exhibits itself in various forms with different ages marking the onset of symptoms. The inheritance patterns plus the severity and sequence of symptoms also vary with each form of SMA. We will explore the more common forms of this disorder.
SMA type 1 is noticeable by the time the child is six months old. Symptoms include “diminished limb movements, lack of tendon reflexes, swallowing and feeding difficulties and impaired breathing”. (Kunci: p. 78) In extreme cases, an affected child develops a twist of the spine including various other skeletal abnormalities. “Affected children are never able to sit or stand and a majority of them die from respiratory failure before the age of 12” (Kunci: p. 78).
SMA type 2 begins after a child is 6 months old. The common symptoms are lack of ability to stand or walk respiratory problems, poor tendon reflexes, hypotonia, and fasciculations. The child may eventually know how to sit but he will never stand. Life expectancy for the disorder varies with some patients being able to live beyond adolescence.
SMA type 3 disease appears between a much wider age group of between 2-17 years. Affected persons have an “abnormal gait and style of walking, inability to run properly, climbing steps, getting up from a chair and a distinct tremble of their fingers” (Oliver: p. 130). The lower limbs are mostly affected.
Primary lateral sclerosis afflicts specifically the upper motor neurons and is more common in men than women. Early-onset is usually reported after the age of 50. Its causes are still unknown. PLS takes place when certain cerebral cortex nerve cells that are responsible for the control of voluntary movement weaken progressively that in turn affecting and weakens the respective muscles. This syndrome is rarely hereditary and progresses slowly over years or decades leading to “stiffness and clumsiness of the affected muscles” (Oliver: p 135). The legs are usually the first ones to be affected “followed by the body trunk, arms and hands, and, finally, the bulbar muscles” (Oliver: p. 135). The symptoms exhibited include difficulty with balance, weakness, and rigidity of the legs, clumsiness, and dragging of feet. A 3-year clinical course is necessary before the disorder can be successfully diagnosed. It is not fatal but the quality of life of the individual is subsequently affected. PLS mostly develops into amyotrophic lateral sclerosis.
Diagnostic Methods
Most of the treatment methods used in MND require a diagnosis to be made early to slow down the onset of the symptoms. Unfortunately, there are no specific tests to diagnose MNDs. The problem is symptoms vary from one patient to the next and in the earlier stages of the disease; these symptoms are similar to a lot of other diseases. Before any neurological examination, a physical examination must be conducted. A neurological exam examines the motor and sensory skills nerve function, “hearing and speech, vision, coordination and balance, mental status, and changes in mood or behavior” (Miller et al: p.56). Further tests are conducted to rule out other diseases and to isolate an MND case. These tests include electromyography (EMG) which is used to diagnose muscle and nerve dysfunction, laboratory screening tests of blood and urine, an MRI to rule out other diseases other than MNDs, a muscle or nerve biopsy to confirm nerve disease or regeneration, and a transcranial magnetic stimulation to stimulate motor activities in certain areas of the body (Miller et al: p.56).
Treatment Methods
As mentioned earlier, MNDs have no standard cure. The treatment methods employed are more of damage control to alleviate the effects of the symptoms on the patient. Supportive treatment is structured towards maintaining the quality of life of the patient. The drug, riluzole, the only approved drug for the treatment of ALS in the US only prolongs a patient’s life by 2-3 months but does not minimize the effects of the symptoms. It works by “reducing the body’s natural production of the neurotransmitter glutamate, which carries signals to the motor neurons.” (Wade: p. 74) Research has shown that too much glutamate slows down nerve signaling by motor neurons. Other drugs available in the market only alleviate the symptoms. “Muscle relaxants such as baclofen, tizanidine, and the benzodiazepines may reduce spasticity” (Miller et al: p. 57). Glycopyrrolate and atropine are used in pseudobulbar palsy disorders to reduce the flow of saliva. “Physical therapy and rehabilitation help in correcting the patient’s posture and minimizes joint immobility, slow muscle weakness and atrophy” (Wade: p. 76). Some patients may need additional rehabilitation for speech and swallowing difficulties. The application of speech synthesizers and wheelchairs may help some patients retain independence. (Wade: p. 76).
Conclusion
Preventative methods for MNDs are not known since the causative agents that trigger them are still also unclear. For the case of hereditary disorders, most family members have their DNA screened to see if they are carriers of the known genes that cause these disorders. For the other disorders, most patients come to know of the disease only through their doctors and by then they are told they have only a couple of months to live. Public awareness programs need to be initiated to sensitize people. Disorders like PLS though not fatal can be controlled if the symptoms are identified early (Silver: p. 239).
References
- Kunci, Ralph W, (2002) Motor Neuron Disease. Philadelphia: W.B. Saunders, pp. 69-78
- Miller RG, Anderson FA Jr, Bradley WG, Bromberg MB, Brooks BR, Mitsumoto H, Munsat T, Ringel SP, and the ALS CARE Study Group, (2000)The ALS Patient Care Database: Goals, design and early results. Neurology, 54(1): pp. 53-57
- Oliver, David, (1995) Motor Neuron Disease: A Family Affair. London: Sheldon Press, pp. 126-139
- Silver Julie, (2003) Postpolio Syndrome. Philadelphia: Hanley & Belfus, pp. 235-239
- Wade, Mary Dodso (2001) ALS—Lou Gehrig’s Disease, Berkeley Heights, NJ: Enslow Publishers, pp. 55-78