What Is ALS? What Causes It? What Are Its Symptoms and Treatment?

ALS (Amyotrophic Lateral Sclerosis) is a neurodegenerative condition that affects motor neurons, that is, the communication of nerve cells with the muscles. Motor neurons are the nerve cells responsible for voluntary muscle movements. Therefore, if for any reason these nerve cells cannot perform their function as they should, the signals transmitted to the muscles weaken and loss of muscle strength develops over time. As the disease progresses, muscle weakness may increase and functions such as moving, speaking and swallowing may be affected. In advanced stages, shortness of breath due to involvement of the respiratory muscles may also occur.
In ALS, the onset of symptoms may vary depending on which motor neurons are affected first. While in some people the disease begins with weakness in the hand or leg muscles, in others it may present with difficulty speaking and swallowing. Because the damage to the motor neurons is progressive, the symptoms may spread to different muscle groups over time. Although the exact cause of ALS is not yet fully known and there is no method that can completely cure the disease, early diagnosis is important for planning symptomatic treatments and supportive care.

What Is ALS?

ALS (Amyotrophic Lateral Sclerosis) is a progressive neurodegenerative condition that affects the motor neurons in the brain and spinal cord. Motor neurons are the nerve cells that enable voluntary muscle movements to take place. The signals transmitted from the brain and spinal cord to the muscles are carried by these cells. When motor neurons are damaged, the muscles cannot receive the necessary signals and begin to lose strength over time. As the disease progresses, muscle wasting (atrophy) may develop and moving may become increasingly difficult.
ALS usually presents with weakness in the hand and leg muscles. For example, the person may begin to have difficulty with everyday movements such as buttoning a shirt, holding a pen or walking. In some people, the disease presents with difficulty speaking and swallowing. The onset of symptoms may vary depending on which muscles are affected first and on the rate of progression of the disease. In the past, ALS was also known by the name of Lou Gehrig, a famous baseball player of the 1920s and 1930s. The loss of strength, frequent slipping, falling and coordination problems Gehrig experienced on the field are well-known examples showing how the disease can affect motor skills.
Although ALS primarily affects the nerve cells that control movement, changes in thinking, decision-making, language and behaviour may also be seen in some people. In some patients, frontotemporal dementia, which can affect thinking and language skills as well as cause personality and behavioural changes, may develop. For this reason, ALS is regarded not merely as a disease affecting the motor system, but as a multifaceted neurodegenerative disorder that may also be accompanied by cognitive and behavioural symptoms.

What Are the Symptoms of ALS?

The symptoms of ALS arise from damage to the motor neurons in the brain and spinal cord. Motor neurons are the nerve cells that enable voluntary muscle movements to take place. Upper motor neurons transmit movement signals from the brain to the spinal cord, while lower motor neurons transmit them from the spinal cord to the muscles. In ALS, the loss of function of upper and lower motor neurons causes the muscles to weaken over time and mobility to decrease.
ALS symptoms vary from person to person; however, the most common symptoms are as follows:

• Weakness in the hands and arms, difficulty holding or gripping objects,
• Stumbling, frequently tripping or falling while walking,
• Difficulty lifting the front part of the foot,
• Difficulty with movements such as climbing stairs or getting up from a chair,
• Muscle cramps, stiffness and involuntary twitching,
• Impaired speech or difficulty pronouncing words,
• Difficulty chewing and swallowing,
• Respiratory problems in later stages.

In approximately 70% of ALS cases, the first symptoms appear as weakness in the arm or leg muscles. For this reason, although it is not a condition originating from the muscles, ALS is also known as a muscle disease. The person may have difficulty even with simple daily tasks such as buttoning a shirt, writing or gripping objects in their hand. When the leg muscles are affected, the foot catching while walking, stumbling and falls may be seen.
In some people, ALS begins with weakness in the muscles that control speech and swallowing. In this condition, called bulbar-onset ALS, speech becoming difficult to understand, difficulty pronouncing words, and chewing and swallowing disorders may be seen. In rarer cases, the disease may also affect the respiratory muscles first.
Damage to motor neurons may also lead to various changes in the muscles. While muscle stiffness and increased reflexes may be seen, muscle wasting, flaccidity and involuntary twitching may also occur. As the disease progresses, functions such as moving, speaking, eating and breathing may be increasingly affected. In some people, changes related to thinking, planning and behaviour may also be seen.

What Are the Stages of ALS?

Because ALS is a progressive disease, symptoms may spread to different parts of the body and become more severe over time. However, the rate of progression of the disease, which muscles it affects first and when new symptoms appear vary from person to person. For this reason, although ALS symptoms are generally classified as early-, middle- and late-stage symptoms, they do not appear in the same order in every patient.

Early-Stage ALS

In the early stage, muscle disease symptoms may be mild. Therefore, it may not always be easy to notice the symptoms early on. Muscle weakness, cramps, muscle twitching and muscle stiffness are among the common symptoms. While difficulty speaking and swallowing occurs in some people, more rarely the disease may present with breathing problems due to involvement of the respiratory muscles.
The muscle group in which the first symptoms appear may also affect the early course of the disease. In ALS that begins with weakness in the arm or leg muscles, daily movements may become increasingly difficult. In ALS that begins by affecting the speech and swallowing muscles, problems with pronouncing words, chewing and swallowing may become prominent earlier.

Middle-Stage ALS

In the middle stage, muscle weakness usually spreads beyond the initially affected region and begins to affect daily life to a greater extent. While some muscle groups largely preserve their function, marked loss of strength may be seen in others. Walking, climbing stairs, holding objects and self-care may become difficult.
Speech and swallowing problems may increase. Weight loss may occur due to inadequate nutrition resulting from problems during swallowing. Shortness of breath may develop as amyotrophic lateral sclerosis affects the respiratory muscles. At this stage, a gastrostomy tube to support nutrition or devices to assist breathing may be considered in order to keep the patient's general state of health stable.

Late-Stage ALS

The late stage of ALS is the phase in which muscle weakness and loss of movement become more pronounced. At this stage, the person's ability to walk, sit, hold their head upright and meet their daily needs independently may be severely restricted. Nutritional support may be needed because of chewing and swallowing problems.
Weakening of the respiratory muscles may make breathing difficult. In this period, depending on the person's condition, methods such as mask-delivered respiratory support or tracheostomy may be considered. The care and treatment plan is arranged according to the person's symptoms and needs.
In some people, ALS may also lead to changes in thinking, planning, decision-making and behaviour. Although rare, ALS may also lead in some people to frontotemporal dementia, which, unlike types of dementia such as Alzheimer's, can appear at earlier ages. Nevertheless, cognitive symptoms may not appear in everyone in the later stages of the disease.

What Causes ALS?

As in many other neurodegenerative diseases, genetic factors, environmental factors and age-related changes in nerve cells may together play a role in the development of ALS. Thanks to studies conducted, it is now known that more than 20 genes play a role in the onset of ALS. On the other hand, ALS is divided into two classes, familial and sporadic; that is, while in some patients the cause is genetic factors, in others there is no known cause. The main causes and risk factors of ALS are as follows:

• Approximately 5–10% of ALS cases have a family history of ALS. In these people, the inheritance of one or more mutated genes from the family causes the disease. In some people, although genetic mutations cause the disease, there is no known family history of ALS.
• Why the nerve cells that control muscle movements are damaged in ALS is not yet fully known. Research indicates that the failure of certain proteins to be processed normally and their accumulation in cells may play a role. In addition, oxidative stress, which arises when free radicals cause damage in cells, and excessive exposure to glutamate, which is involved in communication between nerve cells, may also increase the risk.
• There are various studies showing that the risk of ALS may increase with advancing age. This is because in the vast majority of cases the disease appears between the ages of 55 and 75. However, this does not mean that the disease cannot begin at earlier ages.
• Like age, sex is also considered among the risk factors for ALS. Studies show that the disease is more common in men.Exposure to toxins such as lead and mer
• cury, certain viral infectious diseases or head trauma may increase the risk of the disease.

To what extent which factors play a role in the onset of ALS is not yet known. Current research indicates that genetic characteristics and changes occurring in nerve cells may be important in the development of the disease.

How Is ALS Diagnosed?

The diagnosis of ALS is made by evaluating the patient's medical history, family history, neurological examination findings and the results of tests deemed necessary together. Since there is no single test that definitively demonstrates the disease, the change over time in symptoms such as muscle weakness, muscle wasting and involuntary muscle twitching is taken into account during the diagnostic process. These symptoms may also be seen in other conditions such as multifocal motor neuropathy, cervical myelopathy and multiple sclerosis (MS). For this reason, other diseases that may cause similar symptoms must first be excluded during the diagnostic process.
During the examination, the neurologist investigates whether there is impairment in the functions of the upper and lower motor neurons. The progressive nature of the symptoms and their spread to different muscle groups over time are also important for diagnosis. Although there is no test that definitively demonstrates ALS, specialists frequently make use of the diagnostic method known as the Gold Coast criteria during the diagnostic process.
The Gold Coast criteria used in the diagnosis of ALS are based on progressive deterioration of motor function and on upper and lower motor neuron findings. According to these criteria, a progressive deterioration of previously normal motor function must be observed and this must be established by the medical history or by repeated clinical assessments. In addition, one of the following findings must be present:

• Upper and lower motor neuron findings in the same body region: In this case, dysfunction of both types of motor neuron must be detected in the same region.
• Lower motor neuron findings in at least two different body regions: In this case, the presence of upper motor neuron findings is not required.

Upper motor neuron damage may present with findings such as increased reflexes, muscle stiffness and slowing or impaired coordination of voluntary movements. In lower motor neuron damage, muscle weakness and muscle wasting may be seen. Changes associated with nerve cell damage may also be detected on electromyography (EMG). For the Gold Coast criteria to be met, the symptoms must also not be explained by a disease other than ALS. For this reason, in addition to the neurological examination, EMG, nerve conduction studies, magnetic resonance imaging (MRI) and other investigations deemed necessary are used depending on the patient's findings. Various tests may be performed to support the diagnosis of ALS and to differentiate diseases that may cause similar symptoms:

• Electromyography (EMG): By measuring the electrical activity of the muscles, it helps identify changes due to damage to the motor nerves. It can also be used to detect changes in muscles that do not show obvious findings on clinical examination.
• Nerve conduction studies: These examine how the nerves conduct electrical impulses. They particularly help determine whether the symptoms originate from another nerve disease.
• Magnetic resonance imaging (MRI): The brain and spinal cord are imaged to investigate structural problems that may cause the symptoms. MRI alone does not confirm the diagnosis of ALS; it helps exclude other conditions that may cause similar symptoms.
• Blood and urine tests: These may be requested to investigate other diseases that may cause muscle weakness or other neurological symptoms.

While diagnosing ALS is easier in some patients, the diagnostic process may take longer when symptoms are still at an early stage or the disease is progressing slowly. Therefore, when the initial examination and tests are not sufficient to reach a definitive conclusion, the investigations may be repeated.

How Does ALS Begin?

ALS usually presents with loss of strength in the limbs. Complaints such as a hand losing its dexterity, weakness in an arm or leg, or the foot frequently catching while walking may be the first signs of the disease. In some people, the first symptoms are speech and swallowing problems. Early symptoms may vary depending on the motor neurons and muscle groups affected first.

What Is the Cause of ALS?

Genetic factors are known to play a role in the development of ALS. In approximately 5–10% of cases, the cause is the inheritance from the family of a mutated gene that causes the disease. However, in people without a family history of the disease, genetic changes occurring for various reasons may also lead to the development of the disease.

Is ALS Genetic?

There are more than 20 genes thought to be associated with the risk of ALS. ALS is a condition that can be inherited genetically within families and can also arise without a family history.

Does ALS Cause Pain?

Muscle cramps, muscle stiffness, load on the joints and restricted movement may cause pain.

What Helps with ALS?

Although there is no treatment that completely cures ALS, treatments aimed at slowing the progression of the disease and alleviating symptoms can be applied. In addition to drug therapy, physiotherapy, nutritional support, respiratory support and speech therapy can help make the person's daily life easier.

Can ALS Be Detected in a Blood Test?

There is no blood test that shows ALS on its own. Blood tests can be used to assess general health and whether malnutrition has developed.

What Diseases Are Confused with ALS?

Conditions presenting with muscle weakness, such as myasthenia gravis, multiple sclerosis (MS), primary lateral sclerosis, progressive muscular atrophy and multifocal motor neuropathy, may be confused with ALS. In addition, spinal cord or nerve compression in the neck region, vitamin B12 deficiency and thyroid diseases may also cause similar symptoms.

At What Age Does ALS Begin?

ALS mostly affects people in older age groups. Symptoms usually appear between the ages of 55 and 75. Nevertheless, the disease may also begin at younger ages.

Which Doctor Should Be Consulted for ALS?

When ALS is suspected, a neurologist should be consulted first. If the diagnosis of amyotrophic lateral sclerosis is confirmed, specialists from different branches such as a pulmonologist, a gastroenterologist, a dietitian and a psychologist may become involved in the process.

What Is the Treatment for ALS?

The aim of ALS treatment is to slow the progression of the disease, alleviate symptoms and help the person maintain their daily life as independently as possible. Since the course of the disease varies from person to person, the treatment plan is also prepared according to the patient's symptoms and needs. Although there is not yet a treatment that can completely reverse the damage caused by the disease, the aim is to bring symptoms under control and preserve quality of life with medications and supportive therapies.
ALS treatment is managed with a multidisciplinary approach. In addition to neurologists, physical medicine and rehabilitation specialists, gastroenterologists, dietitians, psychologists and physicians specialised in palliative care may take part in the treatment process. Some medications used in the treatment of amyotrophic lateral sclerosis, particularly when started early, may slow the rate of progression of the disease or minimise the risk of damage to the respiratory muscles. In addition to medications, physiotherapy and rehabilitation may also be used in treatment.
As muscle weakness and restricted movement increase, exercises aimed at preserving joint mobility and facilitating daily activities may be planned. In people who have difficulty walking and moving, assistive devices such as a cane, walker or wheelchair can also make daily life easier. Because the exercises to be performed must be appropriate to the person's muscle strength and must not cause excessive fatigue, it is important that they are planned under a doctor's supervision.
In addition, in patients who begin to have chewing or swallowing problems, adequate nutrition may become difficult and weight loss may be seen. For this reason, the person's nutritional status can be monitored regularly and a nutrition programme suited to their needs can be prepared. When swallowing is not safe or adequate food cannot be taken by mouth, tube feeding may also be considered. In people with speech difficulties, speech and language therapy can be applied. When speech becomes increasingly difficult to understand over time, communication boards can help the person express themselves.
When the disease affects the respiratory muscles and breathing becomes difficult for patients, devices providing respiratory support can be used. Respiratory devices can help prolong patients' survival.
Because the disease is progressive, the treatment plan is reviewed at regular intervals from the time of diagnosis. Additional interventions may be required when necessary.
ALS is a progressive disease that affects the motor neurons, causing muscle weakness and reduced mobility over time. Although a definitive cure for the disease has not yet been found, early diagnosis is important for bringing symptoms under control and for planning supportive care in a timely manner. The evaluation and follow-up process for the diagnosis of ALS is carried out by specialist physicians at the Neurology department of Yeditepe University Hospitals.

Frequently Asked Questions About ALS