AMYOTROPHIC LATERAL SCLEROSIS: SYMPTOMS, CAUSES, AND TREATMENTS - NEUROPSYCHOLOGY - 2025

The lateral sclerosis amiofrófica (ALS) or Lou Gehrin disease is a neurological disease degenerative a progressive cuso that affects motor neurons are located in the brain and spinal cord (The Journal American Medical Association, 2007).

The degeneration of this type of neurons that are responsible for transmitting the orders of voluntary movements to the muscles, causes the brain's ability to initiate motor execution to be lost. Therefore, patients begin to show progressive muscle atrophy, developing severe paralysis (Fundación Miquel Valls, 2016).

Stephen Hawking suffered from ALS

In addition to a motor disability, deficit in the ability to articulate language, swallowing or breathing, recent studies have shown that this type of disease can also appear associated with fronto-temporal dementia processes, showing cognitive and behavioral alterations in the individuals (Fundación Miquel Valls, 2016).

It is a disease with a progressive, invariably fatal course (National Institute of Neurological Disorders and Stroke, 2013). Despite this, the quality of life of patients, and even survival time, can vary significantly depending on the type of medical action used (Orient-López et al., 2006).

Prevalence

In many cases, amyotrophic lateral sclerosis is considered a rare or minor disease. The number of people suffering from this disease is between 6 and 8 people for every 100,000 inhabitants. Despite this, we must bear in mind that the incidence of the disease is 1-3 new cases per 100,000 inhabitants each year (Fundación Miquel Valls, 2016).

ALS is more prevalent in men than in women, in a ratio of approximately 1.2-1.6: 1, and it usually occurs in individuals with adulthood. It is estimated that the mean age of onset is around 56 years of age, and that its presentation is scarce before the age of 40 or after the age of 70 (Orient-López et al., 2006). However, cases of the disease occur in people between 20 and 40 years of age (Amyotrophic Lateral Sclerosis Association, 2016)

On the other hand, the mean duration of the disease is usually three years, reaching a survival of more than 5 years in 20% of those affected and more than 10 years in 10% of these patients (Orient-López et al., 2006).

Generally, more than 90% of ALS cases occur randomly without presenting a clearly defined risk factor. Patients often do not have a hereditary history of the disease, or any member of their family is not considered to be at high risk of developing ALS. Only 5-10% of ALS cases are inherited (National Institute of Neurological Disorders and Stroke, 2013).

Description

Amyotrophic lateral sclerosis is a neuromuscular disease that was discovered in 1874 by Jean-Martin Charcot. He described it as a type of disease in which the nerve cells that control the movement of the voluntary muscles, the motor neurons, progressively decrease their efficient functioning and die, giving rise to weakness followed by severe motor atrophy (Paz Rodríguez et al.., 2005).

Motor neurons are a type of nerve cell that can be located in the brain, brain stem, and spinal cord. These motor neurons serve as centers or control units and link the flow of information between the voluntary muscles of the body and the nervous system (National Institute of Neurological Disorders and Stroke, v).

The information from the motor neurons located at the brain level (called upper motor neurons) are in turn transmitted to the motor neurons located at the level of the spinal cord (called lower motor neurons), and from there the flow of information is sent to each particular muscle (National Institute of Neurological Disorders and Stroke, 2013).

Thus, in amyotrophic lateral sclerosis, a degeneration or death of both the upper motor neurons and the lower motor neurons will occur (National Institute of Neurological Disorders and Stroke, 2002), and therefore they will prevent the chemical messages and essential nutrients that the muscles require for their proper functioning do not reach the muscular areas (Paz-Rodríguez et al., 2005).

Due to the inability to function, the muscles will progressively show weakness, atrophy or contractions (fasciculations) (National Institute of Neurological Disorders and Stroke, 2013).

Specifically, in this pathology there is a specific definition of each of its terms (Paz-Rodríguez et al., 2005).:

• Sclerosis: means "hardening." Specifically, it means hardening of the tissues when a disintegration of the nerve pathways occurs (Paz-Rodríguez et al., 2005).
• Lateral: implies the notion of "side", and refers to the nerves that run bilaetrally in the spinal cord (Paz-Rodríguez et al., 2005).
• Amyotrophic: This term is often used as "related to muscle atrophy." It is a serious degeneration of motor neurons that will cause progressive paralysis of the muscles involved in movement, speech, swallowing or breathing (Paz-Rodríguez et al., 2005).

Symptoms

On many occasions, the appearance can be very subtle, showing signs so mild that they are often overlooked (National Institute of Neurological Disorders and Stroke, 2013).

The first symptoms can include contractions, cramps, muscle stiffness, weakness, impaired speech or difficulty chewing (National Institute of Neurological Disorders and Stroke, 2013). Specifically, they may appear (Amyotrophic Lateral Sclerosis Association, 2016):

• Muscle weakness in one or more of the following areas: upper limbs (arms or hands); lower limbs (specifically legs); of the articulatory muscles of language; muscles involved in swallowing or breathing.
• Tics or muscle cramps, most commonly seen in the hands and feet.
• Inability to use arms or legs.
• Language deficits: like "swallowing words" or voice projection difficulty.
• In more advanced stages: shortness of breath, difficulty in breathing or swallowing.

Progression

The part of the body that will be affected by the first symptoms of amyotrophic lateral sclerosis will depend on which muscles of the body are damaged first (National Institute of Neurological Disorders and Stroke, 2013). So the initial symptoms usually vary a lot from one person to another.

In some cases they may experience stumbling when walking, difficulty walking or running, while other people may have difficulties when they need to use an upper limb, problems lifting or taking objects, or in other cases, stuttering (Amyotrophic Lateral Sclerosis Association, 2016).

Progressively, the involvement in a muscular area or limb spreads contralaterally. Thus, the deficit becomes symmetrical in all four extremities.

Little by little, the evolution of the disease will affect the bulbar level, producing an alteration of the muscles of the neck, face, pharynx and larynx. A serious alteration of the articulation of words and swallowing begins to show, initially with liquids and progressively also with solids (Orient-López et al., 2006).

In the later stages of the disease, when the pathology is in advanced stages, muscle weakness and paralysis extend to the respiratory muscles (Orient-López et al., 2006), patients lose the ability to breathe autonomously and the use of an artificial respirator will be necessary to maintain this vital function (National Institute of Neurological Disorders and Stroke, 2013)

In fact, respiratory failure is the most prevalent cause of death in people with amyotrophic lateral sclerosis, while other causes such as pneumonia are less prevalent (The Journal American Medical Association, 2007).

In most cases, within 3-6 years after the initial presentation of symptoms, the death of the patient usually occurs, although in some cases they tend to live for several decades with this pathology (The Journal American Medical Association, 2007).

Due to the fact that amyotrophic lateral sclerosis primarily affects the motor neurons, somatosenrial, auditory, taste and olfactory function will not be affected. Furthermore, in many cases there will not be an impairment of ocular mobility and sphincter function either (Amyotrophic Lateral Sclerosis Association, 2016).

Causes

The specific causes of amyotrophic lateral sclerosis are not exactly known. In cases where the disease occurs hereditary, genetic factors related to three loci of autosomal dominant transmission (21q22, 9q34 and 9q21) and two of autosomal recessive transmission (2q33 and 15q15-q21) have been identified (Orient- López et al., 2006).

However, a varied number of causes have also been proposed as possible etiological factors of amyotrophic lateral slerosis: environmental, exposure to heavy metals, viral infections, prion diseases, autoimmune factors, paraneoplastic syndromes, etc., although there is no irrefutable evidence of their role (Orient-López et al., 2006).

Some of the pathophysiological mechanisms that have been identified in relation to this pathology are (Fundación Miquel Valls, 2016):

• Reduced availability of neurotrophic factors
• Calcium metabolism disorders
• Excitoticity due to excess glutamate
• Increased neuroinflammatory response
• Changes in the cytoskele
• Oxidative stress
• Mitochondrial damage
• Protein aggregation
• Transcriptional disturbances
• Other factors

Types of amyotrophic lateral sclerosis

Due to this initial description that emphasizes the lack of genetic factors, clinical investigations have proposed several types of amyotrophic lateral sclerosis (Amyotrophic Lateral Sclerosis Association, 2016):

Sporadic

It is usually the most prevalent form of amyotric lateral sclerosis. Specifically, in the United States it occurs in around 90-95% of all cases. However, it is thought that endogenous factors (metabolic and genetic) and exogenous factors (environmental, related to the individual's lifestyle) are involved (Fundación Miquel Valls, 2016).

Family

It is usually due to a dominant genetic inheritance and occurs more than once in a family line. It represents a small number of cases, around 5-10%. The involvement of some genes has been described: SOD1, Alsina, VAPB, TARDBP, FUS, Sechin, OPTN, VCP, ANG, UBQLN2, C9ORF72 (Fundación Miquel Valls, 2016).

Gumaniana

Different studies have observed a high incidence of amyotrophic lateral sclerosis in Guam and the Pacific Trust territories in the 1950s (Amyotrophic Lateral Sclerosis Association, 2016).

Diagnosis

Amyotrophic lateral sclerosis is a difficult disease to diagnose. Currently there is no single test or procedure to make the definitive diagnosis of the disease (Amyotrophic Lateral Sclerosis Association, 2016).

Therefore, the diagnosis of this type of pathology is fundamentally clinical and is based on the demonstration of the presence of signs and symptoms of involvement of motor neurons, such as weakness, atrophy or fasciculation (Orient-López et al., 2006).

A complete differential diagnosis should include most of the procedures listed below (Amyotrophic Lateral Sclerosis Association, 2016):

• Electromyography (EMG) and nerve conduction analysis (NCV).
• Blood and urine tests: These should include serum protein electrophoresis, analysis of thyroid and parathyroid hormone levels, and heavy metal detection.

There are several diseases that can cause some of the symptoms that occur in ALS. Because many of these are treatable, the Amyotrophic Lateral Sclerosis Association (2016) recommends that a person who has been diagnosed with ALS seek a second opinion with a specialized professional, to rule out possible false positives.

Treatment

Currently, experimental studies have found no cure for ALS. So far no cure has been found (National Institute of Neurological Disorders and Stroke, 2013)

The only drug that has proven to delay this pathology is Riluzole (Amyotrophic Lateral Sclerosis Association, 2016). This drug is thought to reduce damage to motor neurons by decreasing glutamate release (National Institute of Neurological Disorders and Stroke, 2013)

In general, treatments for ALS are aimed at alleviating symptoms and improving the quality of life of patients (National Institute of Neurological Disorders and Stroke, 2013).

The most current studies show that comprehensive and multidisciplinary care that integrates medical, pharmaceutical, physical, occupational, speech therapy, nutritionist, social therapy, etc., improves the quality of life of patients affected by ALS and their families, contributing to prolong the evolution of the disease (National Institute of Neurological Disorders and Stroke, 2013; Fundación Miquel Valls, 2016).

References

1. Association, AM (2016). Lateral amyotrofic sclerosis, ALS. The Journal of American Medical Association, 298 (2).
2. Catalan Foundation for Amyotrophic Lateral Sclerosis Miquel Valls. (2016). Obtained from fundaciomiquelvalls.org/es
3. Orient-López, F., Terré-Boliart, R., Guevara-Espinosa, D., & Bernabeu-Guitart, M. (2006). Neurorehabilitative treatment of amyotrophic lateral sclerosis. Rev Neurol, 43 (9), 549-555.
4. Paz-Rodríguez, F., Andrade-Palos, P., & Llanos-Del Pilar, A. (2005). Emotional consequences of caring for the patient with amyotrophic lateral sclerosis. Rev Neurol, 40 (8), 459-464.