Understanding ALS

Amyotrophic lateral sclerosis (ALS) is the most common and most severe degenerative disease in adults within the group of motor neuron diseases (MND). It belongs to a group of chronic, progressive neurological disorders of the motor system, characterized by the loss of motor nerve cells (motor neurons) that control the muscles of the head and body.

ALS is a disease in which motor neurons in the motor cortex of the brain (upper motor neurons) and in the spinal cord (lower motor neurons) progressively degenerate. As a result, the muscles responsible for movement, speech, swallowing, and breathing are unable to function properly and gradually weaken. This is often accompanied by muscle stiffness, increased reflexes, and uncontrolled emotional reactions.

The defining feature of ALS is its progression. It is important to emphasize that the rate and pattern of disease progression vary from patient to patient, as the degree of involvement of motor neurons in the brain and spinal cord—and consequently the muscles—differs among individuals.

In most patients, within three to five years from the onset of symptoms, paralysis of the muscles of the arms and legs occurs, along with loss of speech, swallowing, and breathing ability, which ultimately leads to a fatal outcome.

ALS is also known as Charcot’s disease, named after the neurologist Jean-Martin Charcot, who first fully described the clinical picture and named the disease in 1869. Worldwide, the term “motor neuron disease” is often used as a synonym for ALS, while in the United States it is also referred to as Lou Gehrig’s disease, named after the famous baseball player whose public battle with ALS significantly raised awareness of the condition.

The exact reason why motor neurons in the brain and spinal cord degenerate is still unknown, nor is it clear when this process begins. However, numerous hypotheses have enabled significant progress in understanding the mechanisms behind the onset, development, and progression of the disease. It is believed that, in most patients, ALS develops as a result of a combination of multiple genetic factors and environmental influences.

Risk factors for the development and progression of the disease include:

• male sex
• excessive physical activity
• head injuries
• pesticides
• heavy metals (mercury and lead)

Familial ALS (FALS) occurs in approximately 5–10% of patients and is associated with mutations in specific genes. It is considered to arise primarily from the dominant effect of a single gene, with additional influence from interactions between other genes and environmental factors.

Over a lifetime, the risk of developing ALS is approximately 1 in 300. In the majority of patients, the disease is not inherited and occurs in the form of so-called sporadic ALS, while about 5–10% of cases represent inherited or familial ALS (FALS).

ALS can occur at any age, but it most commonly develops between the ages of 55 and 70 (very rarely before the age of 25). The disease affects men more often than women, with a male-to-female ratio of approximately 1.3–1.5:1.

Globally, 1.5 to 2.7 new cases per 100,000 people are diagnosed each year, and the incidence of the disease is increasing, partly due to longer life expectancy. The total number of people living with ALS at any given time (prevalence) ranges from 3 to 8 per 100,000 population. In Serbia, there are approximately 270 to 300 people living with ALS at any given time, and this number continues to rise.

The average life expectancy of people living with ALS is 3 to 5 years from the onset of the first symptoms. About 20% of patients live longer than 5 years, while one in ten patients lives for more than 10 years.

Symptoms and signs of ALS develop gradually. In the early stages, when most complaints first appear, they are often attributed to fatigue or to age, especially if they occur in the sixth or seventh decade of life. The most common symptoms include:

• Gradual development of weakness in the arm muscles (most often the hands): difficulty turning a key in a lock, dropping objects from the hand (so-called limb/spinal onset).
• Gradual development of weakness in the leg muscles (most often the feet): unsteady gait, tripping over the foot (limb/spinal onset).
• Gradual development of speech difficulties due to weakness of the tongue, throat, and pharyngeal muscles: impaired articulation, slowed tongue movements, “tongue stumbling,” speech sounding like “hot potato speech” (so-called bulbar onset).
• Swallowing difficulties: choking on liquids or food, accumulation of saliva (bulbar onset).
• Uncontrolled emotional reactions: episodes of crying or laughing without a real reason (bulbar onset).
• Breathing difficulties: shortness of breath, shallow breathing, difficulty coughing due to diaphragm weakness (so-called respiratory onset).
• Muscle cramps in the arms or legs.
• Loss of muscle mass in the arms or legs.
• Fasciculations: small, rapid muscle twitches (in the arms, legs, chin, tongue), especially visible when the muscle is at rest.
• Fatigue and exhaustion, present from the very beginning and persistent over time.
• Weight loss due to loss of appetite and/or difficulty swallowing.

Important:
All of these symptoms may also occur in other diseases. Therefore, it is essential to consult a physician for further evaluation. In the first few months (2 to 3 months), symptoms are often mild and may be overlooked by patients.

Very rare symptoms and signs:

• Persistent and severe muscle pain, headaches.
• Loss of bladder and bowel control (other potential causes of these symptoms should be investigated).
• Changes in taste and smell.

ALS is a disease that is difficult to diagnose, as there is no single specific test or procedure that can definitively confirm the diagnosis. From the onset of the first symptoms to the final diagnosis, an average of 10–12 months usually passes (ranging from 6 to 24 months), depending on the form of the disease and how quickly both the patient and physicians respond. There are several reasons for this delay, including late presentation to a primary care physician, failure to recognize the disease in its early stages, long waiting times for neurological consultations, and similar factors. Delayed medical consultation or unrecognized symptoms often contribute significantly to diagnostic delay.

A neurological examination is essential, but in order to confirm the diagnosis of ALS, a series of additional tests must be performed. The main goal is to exclude other diseases that may present with similar symptoms but have a more favorable prognosis. For this reason, it is important for patients and their families to be patient and wait for the results of all necessary investigations.

To establish a diagnosis of ALS, the following evaluations are required:

• Neurological examination – assessment of muscle weakness, muscle wasting, fasciculations, muscle tone, and reflexes during a comprehensive examination of the head, neck, arms, and legs.
• Electromyography (EMG) – a test that records nerve impulses within the muscles. By inserting a small needle electrode into the muscle, its electrical activity is measured. Muscles that are damaged due to insufficient nerve input from the spinal cord show abnormal electrical activity compared to healthy muscles. EMG can detect changes in muscle activity in ALS patients much earlier than a standard neurological examination.
• Magnetic resonance imaging (MRI) of the brain and spinal cord – an important method used to rule out other conditions that may mimic ALS symptoms.
• Laboratory blood tests – very important for excluding other diseases. For example, a mild increase in creatine kinase (an enzyme released during muscle breakdown) may be seen in ALS patients and is not specific, but it is helpful in excluding primary muscle diseases, in which creatine kinase levels can be extremely high.
• Pulmonary function testing – performed to assess the strength of respiratory muscles and is particularly important because ALS patients may not initially experience noticeable breathing difficulties, which these tests can reveal. These tests are mandatory, as abnormal results may also be caused by other conditions such as asthma or emphysema. Pulmonary function tests should be repeated every 3 to 6 months. If patients are unable to perform standard tests due to muscle weakness, arterial blood gas analysis should be performed to evaluate respiratory gases. All of these procedures are carried out in pulmonary clinics.

Learning that you have ALS is an enormous source of stress, both for the patient and for their family. Common and completely normal reactions include shock, disbelief, sadness, anger, and despair. Some people feel the need to talk openly about everything, while others prefer silence and isolation—both responses are natural.

After the initial phase, a period of adjustment and reflection usually follows—about life, family, and future plans. Almost all patients in this situation have difficulty remembering what was said at the time of diagnosis. For this reason, it is often helpful to schedule an additional visit with a neurologist in order to receive all important information again. However, the information a neurologist can provide is necessarily limited, as every patient’s course of illness is different. Therefore, it is important for the patient and family members to begin therapy and planning the next steps as soon as possible.

It is important for patients and their families to understand that nothing will happen “overnight” and that they should continue to live and function in accordance with their abilities. Patients and family members should not burden themselves with thoughts of blame for the onset of the disease. If circumstances allow—especially in the early stages—it is advisable for patients to continue working, socializing, and traveling. It is also expected that patients and their families may feel the need for psychological support, which can be extremely beneficial.

• It is very important to explain to patients and their families that not all information found on the internet is reliable or necessarily applicable; any uncertainties are best discussed with a physician.
• Most importantly, within their abilities, patients should remain focused on themselves, their family, and their friends, and contact their doctor whenever new symptoms arise—whether physical or emotional.
• Coping with ALS is extremely difficult, and it is important to know that you are not alone in this journey—doctors, family, and the community are there to provide support at every step.

I Early Stage

Limb (spinal) onset:
A mild, asymmetric loss of muscle strength in the hand, with difficulties in fine motor skills such as buttoning clothes or writing. If the onset is in the foot, walking difficulties occur, including tripping. Fatigue and muscle fasciculations are present. Patients in this stage are able to function independently.

Bulbar onset:
The first signs are changes in speech, such as “tongue stumbling,” altered articulation, and a soft or hoarse voice. Early difficulties with chewing and swallowing may appear, as well as jaw stiffness.

Average duration of this stage:
Approximately 9–12 months for spinal onset and 6–9 months for bulbar onset, from the appearance of the first symptoms.

II Middle Stage

Spinal onset:
Weakness spreads from one arm to the other or to the leg on the same side. Initial speech and swallowing difficulties may occur. Patients require assistance with daily activities. Falls become more frequent, and walking or standing without aids becomes increasingly difficult.

Bulbar onset:
Communication becomes difficult, swallowing problems become more pronounced, and muscle weakness and wasting appear (most often starting in the arms), along with varying degrees of leg stiffness. Shallow breathing and occasional nighttime choking may occur. Some patients experience episodes of uncontrolled laughing or crying that are not related to genuine emotions.

Onset and duration:
This stage usually begins about 2 years after the first symptoms appear and lasts on average up to 12 months.

III Advanced Stage

Spinal onset:
There is marked weakness or complete paralysis of the arms and legs. Patients lose the ability to care for themselves independently and experience severe difficulties with swallowing, breathing, and speaking. Feelings of sadness, frequent crying, and helplessness are common.

Bulbar onset:
Patients are no longer able to speak and require alternative methods of communication. Swallowing becomes severely impaired, leading to reduced food intake and the need for placement of a percutaneous endoscopic gastrostomy (PEG). Most patients also require home use of breathing machines with a mask, i.e., non-invasive ventilation (NIV), and depend on a wheelchair or remain confined to bed.

Onset and duration:
This stage typically occurs 3 to 4 years after the onset of the first symptoms and lasts on average up to 12 months.

IV Terminal Stage

This stage is characterized by paralysis of the arms and legs, severe loss of muscle mass, confinement to bed, and complete loss of speech. Despite continuous mask ventilation, patients may still experience episodes of choking. Continuous medical care is required, along with sedative and pain-relieving medications. Common complications include pneumonia, pulmonary embolism, and cardiac arrhythmias.

At this stage, a surgical procedure—tracheotomy with placement of a cannula connected to a breathing machine—may be performed, allowing patients to continue breathing via invasive ventilation (IV). This procedure requires careful monitoring and constant care to prevent complications such as infections or blockage of the cannula.

Onset and duration:
This stage occurs 3 to 5 years after the first symptoms appear and lasts on average 2 to 4 months without the use of invasive ventilation (IV).