The central nervous system regulates voluntary movements. Amyotrophic lateral sclerosis (or ALS), a generally known as Lou Gehrig’s disease or Charcot’s disease, causes the degeneration of motor neurons in the CNS (US Department of Health and Human Services (HHS) & National Institutes of Health (NIH), 2017; Wijesekera & Leigh, 2009). A person can control such voluntary movements as walking, running, talking, swallowing, chewing, breathing, and so on. A voluntary movement occurs when motor neurons in the brain (“upper motor neurons”) send an impulse to motor neurons in the spinal cord and motor nuclei in the brainstem (“lower motor neurons”) (HHS & NIH, 2017, p. 1; Muscular Dystrophy Association (MDA), 2014). Then, an impulse is passed to muscles. When a person develops ALS this process disrupts due to the deterioration of motor neurons. In America and Europe, ALS prevalence is 1-2 cases per 100,000 individuals yearly (Brown & AlChalabi, 2017). Although ALS is fatal, its causes, symptoms, diagnosis and treatment still generate numerous questions that puzzle both scientists and physicians.
History
ALS is not a newly-discovered disorder. ALS was mentioned by Jean-Martin Charcot in 1869, but the general public learnt about it when Lou Gehrig, an American baseball player, developed the disease in 1939 (Zarei et al., 2015). Several ALS mysteries have been solved since 1939. The development of technology allowed studying many processes associated with ALS. Scientists have determined that most ALS cases occur randomly, that de novo mutations in proteins, which bind DNA and RNA, are involved, that SOD1 mutations that cause protein misfolding result in 20% of inherited ALS, that cytoskeletal regulators participate in ALS onset and that cellular RNA processing and protein homeostasis are also involved (Narasimhan, 2015). Researchers still need to determine why mutations happen, why motor neurons expire, how to make an ALS diagnosis faster, and answer other questions connected to ALS. Yet, scientists have determined certain factors that may contribute to ALS onset and discovered some genes that constitute hereditary factors.
ALS Types
ALS can be classified based on several characteristics. According to statistics, over 90% of ALS cases are sporadic without any apparent causes and slightly over 5% of ALS cases are hereditary (HHS & NIH, 2017; UCTV, 2012; MDA, 2014; Zarei et al., 2015). ALS instances also differ by the location of their onset. When the first symptoms occur in limbs this ALS type is called “limb onset” and when the first signs include speech or chewing difficulties this ALS type is called “bulbar onset” (HHS & NIH, 2017). Such a difference in symptoms results from the dissimilarity in deteriorating motor neurons. If the brain and brainstem motor neurons are the first to degrade people experience speech slowness or swallowing problems and if the spinal motor neurons are the first to deteriorate people notice weakness or stiffness in their limbs (UCTV, 2012). Both genetic and familial ALS may start either in the brain or in the spinal cord, but the gradual deterioration of motor neurons brings all signs and symptoms, which are typical for this disease. There are also “flail arm” (when upper limbs suffer first) ALS and “flail leg” (when ALS starts in lower limbs) ALS types, which are characterized by different locations of deteriorating motor neurons (Wijesekera & Leigh, 2009). Despite the dissimilarity in ALS types the causes that trigger each type may be similar.
Causes
ALS can affect different people from all walks of life. Usually, ALS occurs in people aged 55 and older and men are more likely to get ill; Caucasians and non-Hispanics are most prone to develop ALS (HHS & NIH, 2017). It is unclear why these ethnic groups are more
likely to develop ALS. Most ALS patients are healthy prior to the onset of ALS. Many people engage in various sports and lead an active way of life prior to the disease (University of California Television (UCTV), 2012; Zarei et al., 2015). There is a theory that muscle overwork can cause ALS and that sportsmen are at a greater risk. Scientists think that genes called “ciliary neurotrophic factor, leukemia inhibitory factor, and vascular endothelial growth factor 2” are possible risk factors in athletes (Zarei et al., 2015, p. 3). There is a connection between ALS and a military service. The occurrence of ALS is twice higher among the Gulf War veterans probably due to their exposure to toxins, for instance lead (HHS & NIH, 2017; MDA, 2014). The belief that environmental pollutants are to blame is supported by a higher ALS rate among men. Most ALS cases are random, but the chance that twins develop ALS is 60% (Brown & AlChalabi, 2017). In genetic ALS mutated genes can be inherited from one or both parents. Such genes as “SOD1, C9ORF72, FUS and TDP43” are often seen in familial ALS (MDA, 2014, p. 19). Genetic ALS runs in families. Many ALS patients have such “misfolded” proteins as “SOD1, FUS and TDP43”, some patients reveal the presence of immune cells in the nervous system, which may indicate the autoimmune nature of their ALS, and mitochondria defects may cause some ALS cases (MDA, 2014, p. 15; Zarei et al., 2015). Scientists develop various theories of ALS onset. They study if viruses may trigger ALS, if glutamate excess may be responsible and if free radicals, radiation, toxic chemicals, smoking or cell suicide are to blame (MDA, 2014; Zarei et al., 2015). Although most ALS cases are random, there are factors that may be studied. Since most ALS patients are older than 50 and male and since military veterans have a higher ALS rate, such factors as ageing, environmental exposure, toxins and occupational hazards deserve a further research.
Signs and Symptoms
ALS signs and symptoms are different in different people. Moreover, some processes in the body, which look like ALS, may be unrelated to ALS or related to another disease. There are some common signs and symptoms of ALS. They are chewing and speaking problems, weakness or stiffness in limbs, muscle twitching (fasciculations), slowness and the loss of movement coordination, cramps, swallowing problems and slurred talking (UCTV, 2012; MDA, 2014; HHS & NIH, 2017). Some symptoms may be characteristic of ageing and in old people are not connected to ALS. Yet, swallowing, chewing and speaking problems are the most significant signs of ALS (UCTV, 2012). Generally, when a person develops Lou Gehrig’s disease he or she experiences the aforesaid physical changes. The continuous deterioration of muscle functions is a definite sign of ALS. When the disease progresses some patients may develop the “pseudobulbar affect” expressed in involuntarily fits of laughing or crying unrelated to people’s emotions (MDA, 2014). This symptom may be associated with the degradation of upper motor neurons that activate facial muscles. ALS may be accompanied by some cognitive problems and a small number of patients have dementia (MDA, 2014; HHS & NIH, 2017). Yet, only a proper physical examination with blood tests and MRI can help to diagnose ALS and rule out other diseases (UCTV, 2012). There is no ALS test that can immediately indicate the presence of the disease, therefore the diagnosis of Lou Gehrig’s disease is a process of the elimination of other illnesses or things that may cause similar symptoms (UCTV, 2012). Thus, although patients with ALS experience certain common symptoms and signs, the actual diagnosis of ALS is complicated and requires many tests and participation of several physicians, because what looks like ALS may turn out to be a different neurological or muscle disease.
Prognosis
ALS is a serious disease, which progresses relatively fast and results in a person’s death. When a person develops ALS his or her motor neurons deteriorate, which results in the degeneration of a person’s muscles involved in voluntary movements. A person with ALS develops muscle weakness and paralysis. This condition typically causes a person’s death within a period of five years (HHS & NIH, 2017). Cases when a person lives longer are extremely rare. Stephen Hawking, who has had ALS since 1963, is a unique example (Narasimhan, 2015). Involuntary muscles of the internal organs and those associated with sexual organs are not affected by ALS. Yet, prolonged immobility impacts the entire body. Patients with limb onset ALS can live for up to five years, while those with bulbar onset ALS can survive for up to three years and only 4% of patients live for over 10 years after they are diagnosed with ALS (Wijesekera & Leigh, 2009). Several factors impact survival rates. People’s age, location of ALS onset and promptness of its diagnosis influence people’s survival (Wijesekera & Leigh, 2009). Nevertheless, it is a fatal disease; therefore steady deterioration and eventual death are inevitable.
Prevention
Basically, ALS prevention is hard, because most people develop it randomly. However, in terms of familial ALS when there is a family history of ALS it is possible to postpone the onset of ALS. Maintaining a healthy lifestyle with a moderate physical activity and proper nutrition may somewhat prevent ALS. Vitamin E slows ALS development (Zarei et al., 2015). Since environmental factors such as toxins, heavy metals and radiation may contribute to the development of ALS, the elimination or reduction of these factors may prevent ALS. According to Itano (n. d.), ALS can be prevented or postponed with rare sugars, namely with D-allose, which delays ALS by stopping the discharge of glutamic acid and preventing the deterioration of lower motor neurons. Generally, ALS prevention as well as its causes requires a further investigation.
Treatment
Unfortunately, Lou Gehrig’s disease is incurable. There is no cure that can stop its progression (UCTV, 2012). Yet, there are measures and interventions that can alleviate a person’s suffering and improve the quality of his or her life with ALS. The care of the patient with ALS requires a team approach. There are many people who can be involved in it. Family members must take an active part in improving the quality of their loved ones’ life (Stewart, 2010). Apart from family members, such physicians as a respiratory therapist, a physical therapist, a nurse, a family caregiver, a speech-language doctor and other healthcare professionals may participate in the care of an ALS patient (UCTV, 2012). An early intervention is required. A patient has to make certain decisions beforehand. Particularly, he or she has to make timely decisions concerning a feeding tube and a lung ventilation device and to think how they will communicate when their speech deteriorates further (UCTV, 2012). Such interventions must be considered before they are necessary to prepare patients for the time when they become unable to inhale or swallow on their own. Patients must be ready for physical deteriorations that are inevitable and get used to the idea of using assisting devices like a feeding tube in the future.
There are various ideas of therapies that may stop deterioration or at least slow it down and prolong a person’s life. Scientists research the possibility of stem cell therapy that is expected to support neurons and slow down their death (UCTV, 2012). Although ALS cannot be cured it is possible to deal with its symptoms and improve a person’s life. Thus, ALS patients with the pseudobulbar affect are prescribed antidepressants and Nuedexta
(MDA, 2014). Numerous medications are being developed to combat other symptoms. Misfolded proteins are fixed with arimoclomol and daraprim, the autoimmune factor is managed with “basiliximab, methylprednisolone, prednisone, tacrolimus and mycophenolate mofetil”, and rasagiline is used to fix mitochondria (MDA, 2014, p. 20-21). In general, ALS treatment aims to maintain muscle functioning, improve the quality of patients’ life and prolong their life for as long as it may be possible.
Postmortem Considerations
A postmortem examination can shed light at ALS mechanisms. An autopsy of a sporadic ALS patient showed lower motor neuron deterioration “with Bunina bodies and phosphorylated TDP-43 positive inclusions” in both the spinal cord and motor cortex (Ito et al., 2016, p. 3511). There are signs of ALS onset in the spinal cord. The postmortem analysis of the spinal cord revealed a decline in mature microRNAs, disruptions in their processing and the evidence of proteins that bind nucleotides and of their participation in the control of microRNAs associated with ALS (Figueroa-Romero et al., 2016). There are proofs of ALS development in the brain tissue as well. Postmortem MRIs can expose changes, which are invisible during in vivo MRIs (Turner & Modo, 2010). Moreover, postmortem and in vivo MRI scans can be compared for a better understanding of ALS progression in the brain.
Conclusion
Amyotrophic lateral sclerosis is a neurologic condition that reduces people’s lifespan and degrades their quality of life. However, many studies help to understand the pathophysiology of the disease and develop medications that alleviate its symptoms. Certain interventions, like feeding tubes and breathing devices, have been developed to improve and prolonged the life of people with ALS. Although there is no cure for ALS, the discoveries of cellular and genetic processes involved in ALS bring hope that a cure may be developed in the near future or that scientists will find a way to stop or slow down muscle deterioration.