ALS (Amyotrophic Lateral Sclerosis): Definition, causes, symptoms, diagnosis and treatment

By Cristiano Antonino On Jun 14, 2023

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of adulthood, caused by the loss of spinal, bulbar and cortical motor neurons, which leads to paralysis of voluntary muscles up to and including respiratory muscles

It is also known as Lou Gehrig’s disease, named after the baseball player whose disease was brought to public attention in 1939.

The etymology of the definition Amyotrophic Lateral Sclerosis clarifies the characteristics of the disease.

The word “amyotrophic” comes from the Greek: “a” corresponds to no, “mine” to muscle and “trophic” means nourishment.

Hence, therefore, “No muscle nourishment”.

When a muscle lacks nourishment, it “atrophies” or wears out.

The adjective lateral identifies the areas in a person’s spinal cord where the parts of the nerve cells that control muscles are located.

As this area degenerates, it causes scar tissue or hardening (“sclerosis”) in the region.

Amyotrophic lateral sclerosis (ALS) can come in two forms

familial (5% of cases), i.e. in different members of the family nucleus, with onset around the age of 63
sporadic (95% of cases) i.e. of unknown etiology, with earlier onset, between 40 and 60 years of age.

In general, there is a slight prevalence of men over women with a ratio of about 1.2-1.5.

Unfortunately, ALS is a rare disease.

There is currently no treatment capable of preventing or defeating this fatal disease.

The prognosis in 50% of patients is about 30 months from the onset of symptoms.

About 20% of patients live for 5 years, 5-10% of patients survive more than 8 years, while cases in which a longer survival is observed are rare.

Death often occurs from paralysis of the voluntary respiratory muscles.

What is ALS

Amyotrophic lateral sclerosis (ALS) affects the motor neuron (or motor neuron), a cell of the central nervous system.

This is why it is also known as “motor neuron disease”.

Motor neurons are the cells responsible for the contraction of voluntary muscles, mainly involved in movement.

But they are also involved in vital functions, such as swallowing, speaking and breathing.

Their degeneration implies the progressive paralysis of the innervated muscles.

The two types of motor neurons that come into play in ALS are upper motor neurons, i.e. those that connect the brain to the spinal cord, and lower motor neurons, i.e. those that connect upper motor neurons from the spinal cord to all the muscles in the body.

In ALS, motor neurons are no longer able to carry electrical information from the brain and spinal cord to the muscle, which becomes inactive (paralysed) as a result.

About 10-15% of patients with ALS also have symptoms of frontotemporal dementia due to degeneration of neurons in this area of the brain.

Amyotrophic lateral sclerosis often begins with muscle spasms and weakness in a limb or difficulty speaking.

ALS progresses to affect all the muscles needed to move, talk, eat and breathe.

Unfortunately, as highlighted above, we are still faced today with an incurable pathology that culminates in death.

Symptoms of amyotrophic lateral sclerosis

Like other diseases of neurological origin, ALS often arises with non-specific symptoms.

The pathology evolves in silence.

ALS occurs when the progressive loss of motor neurons exceeds the compensatory capacity of the surviving motor neurons.

The initial symptoms of ALS can vary greatly from person to person and often include muscle weakness or stiffness.

One person may have difficulty gripping a pen or lifting a glass, while another person may experience a change in her tone of voice when she speaks.

ALS usually has a gradual onset and progression, again, can differ significantly from case to case.

Symptoms can start in the muscles that control speech and swallowing, or in the hands, arms, legs, or feet.

In more detail, the signs of ALS vary in relation to the class of motor neurons involved.

From this point of view, the symptoms connected to the degeneration of the upper motor neurons are

excessive increase in muscle tone (muscular hypertonicity)
exaggerated accentuation of muscle-tendon reflexes (profound hyperreflexia)
abnormal response to the plantar skin reflex (Babinski sign)

The disturbances, however, to be referred to the loss of lower motor neurons are configured as:

decreased muscle tone (muscle hypotonia)
reduction in muscle volume (muscle atrophy)
hyporeflexia (muscles respond less to stimuli)
spontaneous, rapid and regular contraction of one or more muscles, without resulting movement (fasciculations)

The course of the disease

Symptoms that are generally seen as the disease progresses include:

limb weakness
muscle cramps and fasciculations (the connection between motor nerves and muscles is lost, as a result the muscles show spontaneous contractions)
difficulty walking or carrying out usual daily activities
difficulty chewing, swallowing, speaking; weakening of the throat muscles can lead to difficulty speaking (dysarthria) and swallowing (dysphagia). Because of the latter, people sometimes drool and can choke on liquids. Food or saliva can be inhaled (aspirated) into the lungs, increasing the risk of pneumonia (so-called aspiration pneumonia). The voice usually sounds nasal but can also be hoarse
difficulty breathing, when the muscles involved in breathing weaken. Some people need a ventilator for breathing
changes in cognitive and behavioral functions.

However, the pathology does not affect the sensory, sexual, bladder and intestinal functions, which do not undergo any alteration.

Very often, cognitive functions are also preserved: in essence, the patient remains aware of the course of the disease and observes the process that will lead him to paralysis and finally to death.

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Although in most cases people affected by ALS keep cognitive and sensory functions intact, about 50% of them can experience cognitive impairments (difficulties in learning, speaking and concentrating).

Additionally, approximately 10-15% of people with ALS experience severe cognitive and behavioral changes that are diagnosed as frontotemporal dementia (FTD).

There is some evidence that mutations in the C9ORF72 gene are the most common cause of FTD, ALS, and hereditary FTD-ALS.

It is important to highlight that even cases of sporadic ALS (in which no family history is known) are strongly linked to mutations in this gene.

As regards the course of ALS, the first symptoms of the disease can be, for example, myoclonus, i.e. short muscle contractions.

Some muscle stiffness (typically called spasticity), muscle weakness with associated impairment of function of a limb, or nasal tone may be signs.

These general disturbances then translate into more evident forms of weakness or atrophy, such as to lead the doctor to suspect a form of ALS when the extent of the damage is already considerable (60 -70% of motor neurons).

Causes of ALS

Today the exact causes of ALS are not known, however the studies conducted so far suggest that the combined effect of multiple factors is at the origin of the onset of the disease.

Among the factors recognized as involved in the development of Amyotrophic Lateral Sclerosis can be counted

an excess of glutamate (amino acid used by nerve cells as a chemical signal); when its rate is high it causes a hyperactivity of the nerve cells which can be harmful
genetic causes; the familial form and some forms of sporadic Amyotrophic Lateral Sclerosis are due to mutations of genes involved in various physiopathological mechanisms. Among the best known genes is C9orf72, whose mutations are currently the most represented in both familial (40%) and sporadic ALS (20%) as well as in some patients with frontotemporal dementia. Unlike other genes, mutation of C9orf72 can result in both a loss of function of the protein and an acquisition of toxic effects. To date, there are over 30 genes that present a risk of association with ALS; however, there is an inheritance that also includes other gene variants in which the disease is evident only with the presence of more than one abnormal gene
lack of growth factors, whose role within our body is to help the growth of nerves and facilitate contacts between motor neurons and muscle cells
damage of an oxidative type, i.e. resulting from the formation of excess free radicals
the accumulation of altered proteins within the motor neuron; it helps lead the cell to death
toxic-environmental factors; there are various elements (aluminium, mercury or lead) and some substances used in agriculture (herbicides and insecticides) which can cause damage to nerve cells and motor neurons.

Risk factors and predisposition

Furthermore, among the environmental risk factors for ALS we can identify:

the traumas; there is a study by the Mario Negri Institute – conducted on 377 patients and 754 healthy people interviewed from September 2007 to April 2010 – which speaks of a connection between ALS and trauma. In particular, the relationship between the number of traumas and the development of ALS would show a linear trend, as the number of traumas increases, there is a corresponding increase in the risk of developing the disease.
the smoke
intense sporting activity

According to the study, professional footballers would be ill with amyotrophic lateral sclerosis on average twice as many as the general population.

If they play in Serie A, the risk would be 6 times greater.

From this investigation it should not be inferred that sporting activity is harmful in itself.

At certain levels, it can anticipate the onset of amyotrophic lateral sclerosis in genetically predisposed individuals.

The latter could play an important role in the progression of ALS, opening up new perspectives for future therapies.

Through motor nerve biopsy, an innovative diagnostic technique, the protein pTDP-43 has been observed to accumulate within the motor nerves of patients with ALS.

This occurs before the axonal degeneration typical of the disease occurs, suggesting that this early event could contribute to the pathogenesis of ALS and represent a possible future diagnostic biomarker.

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