Thursday, August 19, 2010

ALS - My Quickly Written Term Paper

Of the hundreds of diagnosed and treated diseases, many are incurable with amyotrophic lateral sclerosis being one of the more horrific. One morning a patient, more than likely a male, between the ages of 45 and 60, wakes up to find his feet numb, hands tingling, with a twitch in the eyes or tremors in the hands, and perhaps, trouble swallowing.

Those symptoms reflective of motor neuron death or degeneration, are investigated by a physician via family history interview, nerve testing, MRI, and other neural imaging devices. Because there is no specific laboratory test for ALS, by eliminating other potential diseases such as muscular dystrophy or multiple sclerosis, those diseases which likewise affect the motor skills and nervous system, a diagnosis of amyotrophic lateral sclerosis can be made. ALS, or Lou Gehrig's disease, is defined as a motor neuron disease and specifically affects the upper motor neurons contained in the brainstem and cerebral cortex, and the lower motor neurons contained in the spinal cord. Both must be present in order for ALS diagnosis (Figure 1).

Sadly, as the disease progresses it does not decrease the intellectual capacity of the individual enabling the patient to be fully cognizant of their decreasing physical capacity leading quite often to severe depression. Simple movements such as turning over during sleep, or picking up a fork, or turning the head to look at something is impossible. The unable body cannot react to the very able mind.

From the point of first acknowledged symptom to death, the average life expectancy is between three and five years for there is no cure and treatments available are not substantially life prolonging, only quality enhancing and symptom reducing.

ALS was first defined and diagnosed by a Jean-Marie Charcot, a neurologist, in 1874. For almost 140 years since that definition, no specific cause has been found although many theories exist and are being investigated. Because the disease affects humanity with almost complete randomness, one theory that has caught the attention of scientists involves chromosome 21 and the gene encoding for the enzyme, superoxide dismutase, SOD1.

In normal functioning SOD1, the protein takes reactive oxygen and converts it into water. However, in ALS, missense mutations of the gene have been noted to cause about 50% of the familial cases of ALS which amounts to roughly 2.5% of the patients today. These gene mutations cause misfolding of the protein SOD1 which gave scientists the first clue given that protein shape determines function. Researchers investigating the folding of the protein found that deposits built and either caught other proteins necessary for cell health from getting to their destination, or built up to a toxic level eventually leading to cell death (apoptosis). The apoptosis of these specific cells along the neural pathways, causes a demyelination of the nerve (Figure 2).

In June 2009, researchers found that faster clumping of the protein led to faster progression of the disease leading them to hypothesize that the SOD1 mutation is missed during a cell's normal "house cleaning" activity.(15) Evidence is accumulating that glutamate is aggregated amongst the SOD1 protein and causing toxicity.(16) This finding would allow researchers to target drugs at intercepting this aggregation and stop the progression of the disease.(17) The continued hope is that finding a treatment for the familial ALS will help direct treatment for the other patients as well. (18)

The worldwide estimated ALS incidence level is .0024% or 2.4 people per 100,000.(19) The disease has no definitive boundaries related to geography, overall health, diet, race, climate, or socio-economic factors.(20) Common characteristics of the disease as it progresses include trouble with: dysphagia (swallowing), dysarthiria (speaking), spasticity (tight and stiff muscles), hyperreflexia (over excited reflexes including Babinski's sign), and fasciculation (muscle twitching).(21) In addition, loss of muscle tone leads to constipation, lack of normal functioning ability leads to fatigue and depression.(22) Muscle tone also affects the individual's ability to breathe and eventually, in most cases, respiratory failure due to the inability of the muscles to aid breathing, or choking on food, is what leads to death.(23)

While no known causation is seen between various life factors, economic factors could dictate how much palliative care assistance an individual is able to obtain. As of 2009, the only drug approved for treatment of ALS by the FDA is Riluzole which has been shown to block the release of glutamate.(24) At a cost of approximately $10,000 a year with a limited increase in life of 2 months, other economic concerns include: motorized wheel chairs, electronic lifts for motorized vehicles, depression medications, and eventually, hospice or palliative care professionals.(25) Many families are not equipped financially to pay for the additional costs which also leads to depression among family and friends.(26)

The impact of ALS on the individual notwithstanding, the disease greatly affects the primary care giver, family, physicians who treat the individual, and friends. Difficult to watch, harder to grasp the deteriorating condition of a loved one is painful. ALS is insidious as it robs the person of their physical ability to interact with others normally; the patient's mind fully comprehending the fatality of the disease.

CREDIT TO WHERE CREDIT IS DUE! (1-7, 9, 14-18, 20-23) (Figure 1) (8)

Gerard Dynes, Christopher Schwimmer, Susan Staugaitis, John Doyle, Arthur Hays, Hiroshi Mitsumoto (2000, November 13). Amyotrophic lateral sclerosis with multiple sclerosis: A clinical and pathological report. Retrieved from (19) (Figure 2)

Kumar, Vinay, Hogge, Alice & Baer, Arthur (2007). Robbins Basic Pathology - 8th Ed. Philadelphia. (10 - 13)

Miller RG, Mitchell, JD, Lyon M, and Moore DH (April 2003). Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Neurology. Retrieved from (24-26)

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