Amyotrophic Lateral Sclerosis - Term Paper Example

Amyotrophic Lateral Sclerosis Amyotrophic Lateral Sclerosis commonly known as ALS is the most common progressive neurodegenerative disease. In the U.S, ALS is known by the name Lou Gehrig’s disease after the famous Yankees baseball player who was diagnosed with the disease in the middle of his surging career. The greatest physicist Stephen Hawking is also affected by this disease. The life expectancy is about 3 years after the onset of the symptoms; however for about 5% of the patients the life expectancy maybe be increased by anything from a few months to a few decades (Gordon). Physiology of ALS The central nervous system of the human body comprises of the brain and the spinal cord, while the nerves present all throughout the body e.g. in the arms, legs etc are known as the peripheral nervous system. Neurons are the basic components of a nervous system and those neurons that control voluntary muscles owing to chemical signals are known as motor neurons. In this disease the motor neurons of the body are targeted and degenerated gradually. Both upper body neurons and the lower body neurons are targeted. Since, the motor neuron control voluntary muscles, the muscles of the body are also affected. Pathogenesis of ALS It is believed that ALS is genetic in nature and occurs as a result of genetic mutations. The familial form of ALS is caused when the gene coding for the enzyme ALS1/SOD1 mutates while the sporadic form is caused when the gene coding for ALS2 mutates. “Mutations in SOD1 and its protein product initiate motor neuron disease through one or more toxic properties” (Pasinelli & Brown, 712-719). Several pathogenesis hypotheses have been proposed for this disease which includes oxidative stress, excitotoxicity, autoimmunity etc. The oxidative stress pathogenesis hypothesis is the key hypothesis which states that the mutant ASL1 enzyme catalyzes and enhances the production of hydroxyl radical, superoxide anions and other reactive oxygen species which damage the motor cells. Excitotoxicity is yet another valuable hypothesis which involves excitotoxicity of glutamate. Glutamate toxicity causes misbalance of calcium homeostasis inside the cells and increases the production of free radicals too leading to death of neurons. The hypothesis of autoimmunity phenomena on the other hand, is based upon the presence of autoimmunity present in sporadic ALS patients at the neuromuscular junctions of the brain as well as the spinal cord. Population Involved “ALS is found in people all over the world and has an incidence of about one per 100,000 of the population. At any given time, it is likely that about five people in 100,000 will be suffering from ALS” (Jacoby & Youngson,1257-1262) According to reports produced by the National institute of Neurological disorders and stroke almost 30,000 U.S. citizens have been diagnosed with ALS and the number increases each other by another 5000 new cases. People between the age brackets of 40-60 are more likely to develop the disease than others. Men are more vulnerable to disease than women. (National Institute of Neurological disorders & Stroke) Clinical presentation: Clinical features The symptoms of ALS appear in due course of time but are often mistaken for other neural diseases. The very first noticeable symptoms of the disease is the experience of weakness in certain areas especially in the bulbar, cervical, thoracic and lumbosacral regions of the body, which them slowly progresses to other parts.. The involvement of the bulbar region is crucial in proving the adverse effect on cranial nerves number IX, X, XI and XII which indirectly affects the muscles that these nerves innervate (tongue, larynx, pharynx and palate). Therefore with the onset of the symptoms in the bulbar region, the patient experience slurry speech, voice hoarseness and may choke during meals. The upper limb onset of the disease causes frequent cramping, stiffness and reduced working ability of the fingers. These signs appear after the destruction of the motor neurons present in brain (Betz neuron) and destruction of corticospinal tracts. Lower limb onset causes frequent tripping, falling and change in gait of the patient. This happens when the spinal cords anterior horn cells and the cell bodies belonging to motor cranial nerves are destroyed. With gradual progress of the disease to other body parts the symptoms become more severe and widespread. Some of the symptoms that indicate a progresses ALS case include painful joints, frequent cramping of muscles, dysarthria, and hypernasality in speech, loss of speech, dysphagia and drooling effects. One of the most unique features of ALS is the involuntary and inappropriate emotional responses where sudden and frequent changes in emotional expression are seen. For example the patient may laugh at something and immediately cry about the same thing and end up laughing again. DIAGNOSTIC TESTS ALS is a complex disease especially because the symptoms are often mistaken for other diseases therefore no direct diagnosis is available. Besides clinical presentation, the diagnosis depends on several tests that can be performed that can help to rule out the possibility of other diseases. Electromyography is one of the very first tests conducted to establish the presence of ALS in the body. Electromyography presents a study of electrical activity of the muscles. Certain EMG results like spontaneous activity, diffuse denervation etc supports the presence of ALS especially that of the lower motor neurons. The presence of ALS can also be established with the help of important neuroimaging tests such as CT scans and MRI scans. These scans are considered to be valuable diagnostic tools for testing ALS because they help in confirming the absence of other similar neural diseases which share common symptoms with ALS. In case the symptoms of the patients are too confusing, blood tests as well as urine tests are also performed. Blood tests for the levels of immunity protein such as IgA, IgM and IgG are done to rule out the possibility of participation of immunological response in the disease. Myasthenia gravis is a disease that also causes symptoms similar to that of bulbar neuron degenerations therefore blood tests for antibodies against acetylcholine receptors is conducted to rule out the possibility of myasthenia gravis. The results of all these tests help to rule out the possibility of any muscular diseases, thereby confirming ALS. In an ALS patient all hematological tests and urine test results must be normal. Biopsy tests are not performed regularly but in selected cases where diagnosis poses a problem. Both muscle and nerve biopsies are taken to rule out possibility of other neurodegenerative diseases or diseases like body myositis which initiate symptoms somewhat similar to ALS. CURRENT TREATMENTS Till date there is no cure for ALS, however certain pharmacological interventions can help control the symptoms of the disease. The action of medication and the results on the body differs from patient to patient. In the present times, Riluzole is the sole drug approved by the FDA for the treatment of the disease. The efficacy of this drug has been tested in laboratory setting with placebo tests and has been found to be effective. The exact working of the drug is not known however the drug is neuroprotective in nature and reduces glutamate. Several drugs for symptom management have been introduced for example valium for pain, Lioresal and Zanaflex for spasticity, Mestinon for fatigue etc. Speech therapy is often used in ALS patients who suffer from speech problems and are guided by speech therapists to be able to speak louder and clearer. Physical therapy is used to increase the quality of life of the patient. Motion exercises help get rid of muscular impairments and strengthen the weak muscles. Pain management can be done by massaging the sore areas however; transcutaneous electrical nerve stimulation is also used to reduce pain in the patient. CURRENT RESEARCH The current research endeavors aims to correctly identify the cause of the disease, analyze and understand its nature and develop effective treatments for it. Research is being done on the mechanisms behind the selective neuron degeneration in the body by studying the role of SOD1 mutations in animals. Since one of the prime hypothesis suggest the excessive accumulation of free radicals cause the disease, the factors which lead to this is being closely studied. Researches on genetic studies are also on to detect role of other genes except SOD1 because some ALS patients have shown no genetic mutation in their SOD1 gene. Identification of other gene responsible for the disease will make development of diagnosis and other tests much easier. The phenomena of programmed cell death or apoptosis is also being widely studied since apoptosis selectively destroys cells researchers are of the opinion of the presence of some trophic factors behind this phenomena which may also be relevant to ALS and other neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. No genetic biomarkers have yet been developed for the detection of ALS, but work is being done to develop a suitable biomarker. Work on development of better therapies to increase the life quality of ALS affected patients, are also on. FUTURE TREATMENTS The research conducted on this enigmatic disorder has paved way for possible treatments in the near future. A number of pharmacological treatments and other therapies are in the pipeline and shall be released in the coming years. For example, launch of Avicenna’s ALS-02 is set to reveal in 2015 while Mitsubishi Tanabe’s Radicut is set for release in the same year. However, these treatments are add-on to Riluzole (Bates n. p.). Stem cell research also promises to treat ALS effectively where they may be used to replace degenerated neurons with new ones generated from stem cells. The discovery of iPS (induced pluripotent cells) in 2007 was a ground breaking discovery which is a possible treatment for ALS. Researchers at Harvard have already conducted experiments to convert iPS into motor neurons. Therefore, the current state of research seems quite promising and there is a good possibility that in the near future, ALS will become a treatable disease. Works Cited Bates, C. "Future treatment of ALS." PMLive. Feb. 2013: n. pag. Web. 16 Mar. 2013. . Gordon, P. H. "Amyotrophic lateral sclerosis: pathophysiology, di. [CNS Drugs. 2011] - PubMed - NCBI." National Center for Biotechnology Information. N.p., 25 Jan. 2011. Web. 17 Mar. 2013. < http://www.ncbi.nlm.nih.gov/pubmed/21128691> Jacoby, D., and R. Youngson.”Motor Neuron Disease.” Encyclopedia of Family Health - Vol. 9. New York: Marshall Cavendish, 2005.1257-1262 Print. National Institute of Health. "Amyotrophic Lateral Sclerosis (ALS) Fact Sheet: National Institute of Neurological Disorders and Stroke (NINDS)." National Institute of Neurological Disorders and Stroke (NINDS). N.p., n.d. Web. 17 Mar. 2013.< http://www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/detail_ALS.htm> Pasinelli, P., and R. H. Brown. "Molecular biology of amyotrophic lateral sclerosis: insights from genetics." Nature 7 (2006): 712-719. Web. 15 Mar. 2013.< http://www.researchals.org/uploaded_files/pasinelli_nns_rev_0906_844ub6.pdf> Read More