Amyotrophic lateral sclerosis symptoms and treatment methods

Amyotrophic lateral sclerosis (ALS) is an irreversible neurodegenerative disease characterized by primary damage to the upper and lower motor neurons (nerve cells that carry out motor coordination and maintain muscle tone).

Damage to the lower motor neuron leads to a progressive decrease in tone and, as a result, muscle atrophy, while damage to the upper motor neuron leads to the development of spastic paralysis and the appearance of pathological reflexes.

Amyotrophic lateral sclerosis was first described in 1869 by Jean-Martin Charcot. ALS is often called Lou Gehrig's disease, named after the famous baseball player who was diagnosed in 1939.

The disease is rare, however, the reliable incidence of ALS is unknown: in European countries, the incidence, according to various sources, ranges from 2 to 16 cases per year per 100,000 population, while international studies indicate 1–2.5 cases. Men get sick more often; manifestation usually occurs at the age of 58–63 years in the sporadic form; the hereditary variant of ALS often debuts at the age of 47–52 years.

Stephen Hawking is a famous scientist diagnosed with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis affects approximately 350,000 people worldwide each year, approximately half of whom die within 3 to 5 years of diagnosis.

Synonyms: amyotrophic lateral sclerosis, motor neuron disease, motor neuron disease, Charcot's disease, Lou Gehrig's disease.

Amyotrophic lateral sclerosis is an incurable, steadily progressive disease.

Characteristics of the pathology

ALS is a disease that develops in patients of working age, which determines the importance of early diagnosis. The pathology occurs with a frequency of 2-5 cases per 100 thousand population. Men get sick more often. ALS accounts for 80% of the total number of motor neuron diseases. ALS disease has no cure. More often, the cause of death of the patient is associated with respiratory failure caused by infectious lesions of the respiratory tract or paralysis of the respiratory muscles.

Amyotrophic lateral sclerosis, also called ALS, is a disease that in 10% of cases manifests itself as progressive bulbar palsy, which indicates damage to the nuclei that form the basis of the cranial nerves. Muscle atrophy is detected in 8% of patients and is also progressive.

Causes of ALS

For what reasons amyotrophic lateral sclerosis begins to develop, modern medicine cannot give an exact answer. Scientists have only yet established that the cause of the development of this disease lies in pathological disorders of DNA formation. A large amount of 4-stranded DNA appears in the body, and this factor disrupts protein synthesis. A mutation occurs in a protein called ubiquin, as well as in genes. How this factor affects motor neurons has not yet been established, which is why it is difficult to correctly diagnose ALS. In case of suspicion, the patient must be examined by several specialists.

Types of amyotrophic sclerosis

ALS disease is a pathological condition that is accompanied by progressive damage and death of motor neurons, which causes increasing impairment of motor function. The patient cannot breathe, walk, swallow, or talk. Depending on the zone of the primary (debut) lesion, cervical, thoracic, lumbar, and diffuse forms are distinguished.

Based on the rate of increase in symptoms, fast-flowing, medium-flowing and slow-flowing forms are distinguished. O. Khondkarian's classification, taking into account the localization of the onset pathological focus, involves the identification of lumbosacral, cervicothoracic, bulbar, and cerebral types.

Lumbosacral

Occurs with a frequency of 20-25% of cases. The onset of the pathology is accompanied by lower paraparesis (mild paralysis affecting both legs) with subsequent progression.

Cervicothoracic

Detected in 50% of patients. It manifests itself as paresis of mixed type in the upper extremities and spastic type in the lower extremities.

Bulbar

Diagnosed in 25% of patients. The pathogenesis is based on damage to the nuclei that form the basis of the cranial nerves (caudal group). It manifests itself with signs characteristic of damage to the cranial nerves, followed by the addition of pyramidal disorders. Typically, progressive amyotrophy is observed - dysfunction of nerve cells leads to the development of muscle weakness up to complete immobilization of the patient.

Cerebral

Occurs with a frequency of 1-2% of cases. It is manifested by the selective nature of damage to motor neurons with the appearance of symptoms - pseudobulbar syndrome in combination with tetraparesis and spastic paraparesis. Peripheral motor neurons are slightly damaged. The pathological process is localized mainly in the region of the central anterior gyrus, along the entire length of the corticospinal and corticobulbar tracts.

Forms of the disease

The forms of the disease are distinguished by the location of the damaged muscles.

Bulbarnaya

The cranial nerves (9,10,12 pairs) are affected.
Patients with the bulbar form of ALS begin to have problems with speech, they complain of difficulties in pronunciation, and it is difficult for them to move their tongue.

As the disease progresses, the act of swallowing is impaired, and food may pour out through the nose. At a late stage of the disease, the muscles of the face and neck completely atrophy, facial expressions disappear, and patients with ALS cannot open their mouths or chew food.

Cervicothoracic

The disease progresses in the upper limbs on both sides.
Initially, discomfort appears in the hands, and it becomes difficult for a person to perform complex movements with his hands, write, or play musical instruments. Upon examination, the doctor notices that the patient’s arm muscles are tense and tendon reflexes are increased.

In later stages of the disease, muscle weakness progresses and spreads to the forearms and shoulders.

Lumbosacral

The first symptom is weakness in the lower extremities.
It becomes more difficult for the patient to do work while standing, climb stairs, ride a bicycle, and walk long distances.

Over time, the foot begins to sag, the gait changes, then the leg muscles completely atrophy, the person cannot walk, and urinary and fecal incontinence develops.

Almost 50% of patients suffer from the cervicothoracic form of ALS, 25% each account for the lumbosacral and bulbar forms.

Causes

The causes of amyotrophic lateral sclerosis are not fully understood. Pathogenetic mechanisms are constantly being studied, which is associated with the emergence of many theories and hypotheses:

1. Glutamate excitotoxicity. The pathogenesis is based on malfunctions of the glutamate-aspartate system, which provides the transport function. As a result of disturbances, excitatory acids accumulate in the motor areas of the central nervous system.
2. Autoimmune reaction. The pathogenesis is based on the production of antibodies to calcium channels, which triggers a series of reactions leading to the death of motor neurons.
3. Deficiency of neurotrophic factor - proteins that stimulate and support the development of neurons.
4. Mitochondrial dysfunction. The pathogenesis is based on increased permeability of mitochondrial membranes.

Neither theory is supported by conclusive evidence. In 90% of cases, the disease develops spontaneously, sporadically. In 10% of cases, the causes of ALS correlate with hereditary predisposition. In patients with a hereditary form, a mutation of the SOD-1 enzyme (superoxide dismutase enzyme) is detected in 20% of cases.

The SOD-1 enzyme is involved in regulating the amount of free radicals. Amyotrophic lateral sclerosis is a disease, the development of which in most cases occurs spontaneously, but under the influence of favorable conditions, which allows us to identify risk factors:

• Age over 50 years.
• Hereditary predisposition.
• Male gender.
• Bad habits (smoking, alcoholism).
• Residence in rural areas (correlation with negative health effects of pesticides used in agriculture).

Amyotrophic lateral sclerosis syndrome is characterized by clinical heterogeneity (heterogeneity), which leads to many options for describing the clinical picture in practical neurology. Heterogeneity is manifested in the localization of the onset pathological focus, the nature of the spread of the pathological process, the variability of the combination of symptoms, and the rate of progression of neurological deficit.

Drug treatment

Because Lou Gehrig's disease cannot be reversed, all treatments are intended only to relieve symptoms, prevent complications, and improve the patient's quality of life as much as possible.

The drug, called Riluzole, is the only drug approved for use in ALS by the Food and Drug Administration. Riluzole slows the progression of the disease by reducing the level of a neurotransmitter (glutamate) in the brain. This drug may cause side effects such as dizziness and problems with the gastrointestinal tract and liver.

Your doctor will likely prescribe medications to relieve other symptoms:

• Muscle cramps and spasms.
• Muscle spasticity.
• Constipation.
• Fatigue.
• Increased salivation.
• Increased sputum production.
• Pain.
• Depression.
• Sleep disorders.
• Involuntary bouts of laughter or tears.

Symptoms

ALS syndrome is a complex of symptoms associated with destructive processes in the tissues of the brain (brain, spinal column), which determines the nature of the manifestations, including symptoms that arise as a result of the destruction of neural connections. In amyotrophic lateral sclerosis, 80% of neurons are irreversibly damaged before significant clinical signs of the disease appear, making early diagnosis difficult. ALS symptoms at a young age in the early stages of its course:

• Convulsions, twitching in the limbs.
• Weakness in the limbs.
• Numbness and other sensitivity disorders in muscle tissue.
• Speech deterioration.

These signs are characteristic of many diseases of the central nervous system, which significantly complicates the formulation of a differential diagnosis. The prodromal (preceding the appearance of severe symptoms) period in isolated cases can last up to 1 year. The disease is characterized by a rapid increase in clinical signs. Symptoms of ALS syndrome:

1. Fasciculations (muscle twitching).
2. Peripheral paralysis (atony - decreased muscle tone, immobility, areflexia - absence of natural involuntary reactions to stimuli).
3. Pyramidal disorders (presence of pathological reflexes - oral automatism, hand and foot, clonus - rapid, rhythmic contraction of a muscle group, synkinesis - reflex involuntary movement of a limb in response to voluntary movement of the opposite limb).
4. Bulbar syndrome (dysarthria - speech impairment, dysphagia - difficulty swallowing, muscle atrophy in the tongue, respiratory rhythm disorder).
5. Pseudobulbar syndrome (symptoms characteristic of bulbar syndrome, the difference is that paralyzed muscles do not undergo atrophy).

Symptoms of amyotrophic lateral sclerosis do not differ between sporadic and familial (hereditary) forms. The onset manifestations depend on the localization of the area of ​​damaged nerve structures. If the pathological process is localized in the area of ​​the lower extremities (75% of cases), amyotrophic sclerosis is accompanied by awkwardness when walking and deterioration of flexibility in the ankle joint.

As a result, the gait changes, the patient stumbles, and has difficulty maintaining body balance. Primary damage to the upper extremities is associated with deterioration in fine motor skills of the hands, which causes difficulty in performing precise movements that require flexibility and dexterity. Gradually, the weakness, which is initially observed in the muscles of the arms, spreads to all parts of the body.

Bulbar and pseudobulbar syndromes are detected in 67% of cases, are difficult to correct, and often lead to the development of aspiration-type pneumonia (associated with the entry of foreign liquids and other substances into the respiratory tract) and opportunistic infections provoked by opportunistic viruses and bacteria. Symptoms of early stage ALS include dysarthria, which may be mild (hoarseness).

The spastic form occurs with the development of rhinophony - an excessive nasal tone of the voice. Progressive dysphagia in amyotrophic lateral sclerosis is often the cause of the development of nutritional dystrophy (protein-energy malnutrition) with symptoms: atrophy of muscles and subcutaneous fat, excessively dry skin, weight loss, and the formation of loose skin folds.

Another pathology that often occurs as a result of dysphagia is secondary type immunodeficiency. It manifests itself as a chronic, recurrent course of upper respiratory tract infections, hematological deficiency, and the formation of autoimmune and allergic reactions. Some patients are diagnosed with frontotemporal dementia. In this form of dementia, cortical (cortical) neurons degrade and behavioral and personality disorders occur.

Symptoms of ALS

Progressive muscle weakness in the legs leads to the patient's inability to move independently.
To find out what clinical manifestations Charcot's disease may have, you should understand what central and peripheral motor neurons are.

The central motor neuron is located in the cerebral cortex. If it is affected, muscle weakness (paresis) develops in combination with an increase in muscle tone, reflexes intensify, which are checked with a neurological hammer during examination, pathological symptoms appear (specific reaction of the limbs to certain irritations, for example, extension of the 1st toe during line irritation outer edge of the foot, etc.).

The peripheral motor neuron is located in the brain stem and at various levels of the spinal cord (cervical, thoracic, lumbosacral), i.e. below the central one. With the degeneration of this motor neuron, muscle weakness also develops, but it is accompanied by decreased reflexes, decreased muscle tone, the absence of pathological symptoms and the development of atrophy of the muscles innervated by this motor neuron.

The central motor neuron transmits impulses to the peripheral one, which transmits impulses to the muscle, and the muscle contracts in response to this. In the case of ALS, at some stage the transmission of the impulse is blocked.

In amyotrophic lateral sclerosis, both central and peripheral motor neurons can be affected, in various combinations and at different levels (for example, there is degeneration of the central motor neuron and peripheral motor neuron at the cervical level or only peripheral motor neuron at the lumbosacral level at the onset of the disease). This is what determines what symptoms the patient will have.

The following forms of ALS are distinguished:

• lumbosacral;
• cervicothoracic;
• bulbar: with damage to a peripheral motor neuron in the brain stem;
• high: with damage to the central motor neuron.

This classification is based on determining the predominant signs of damage to any of the neurons at the onset of the disease. As the disease continues to exist, it loses its significance, because more and more motor neurons at various levels are involved in the pathological process. But such a division plays a role in establishing a diagnosis (is it ALS at all?) and determining the prognosis for life (how long the patient is expected to live).

Common symptoms characteristic of any form of amyotrophic lateral sclerosis are:

• purely motor disorders;
• absence of sensory disorders;
• absence of disorders of the urination and defecation organs;
• steady progression of the disease with the capture of new muscle masses up to complete immobility;
• the presence of periodic painful cramps in the affected parts of the body, they are called cramps.

Lumbosacral form

With this form of the disease, two options are possible:

• the disease begins only with damage to the peripheral motor neuron located in the anterior horns of the lumbosacral spinal cord. In this case, the patient develops muscle weakness in one leg, then it appears in the other, tendon reflexes (knee, Achilles) decrease, muscle tone in the legs decreases, atrophy gradually forms (this looks like weight loss in the legs, as if “drying out”) . At the same time, fasciculations are observed in the legs - involuntary muscle twitching with a small amplitude (“waves” of muscles, muscles “moving”). Then the arm muscles are involved in the process, their reflexes also decrease, and atrophy forms. The process goes higher - the bulbar group of motor neurons is involved. This leads to the appearance of symptoms such as difficulty swallowing, blurred and unclear speech, a nasal tone of voice, and thinning of the tongue. Choking occurs when eating, the lower jaw begins to sag, and problems with chewing appear. There are also fasciculations on the tongue;
• at the onset of the disease, signs of simultaneous damage to the central and peripheral motor neurons that provide movement in the legs are revealed. In this case, weakness in the legs is combined with increased reflexes, increased muscle tone, and muscle atrophy. Pathological foot symptoms of Babinsky, Gordon, Schaeffer, Zhukovsky, etc. appear. Then similar changes occur in the hands. Then the motor neurons of the brain are also involved. Disturbances in speech, swallowing, chewing, and twitching in the tongue appear. Violent laughter and crying join in.

Cervicothoracic form

Can also debut in two ways:

• damage to only the peripheral motor neuron - paresis, atrophy and fasciculations appear, decreased tone in one hand. After a couple of months, the same symptoms appear in the other hand. The hands take on the appearance of a “monkey’s paw”. At the same time, increased reflexes and pathological foot signs without atrophy are detected in the lower extremities. Gradually, muscle strength decreases in the legs, and the bulbar part of the brain is involved in the process. And then blurred speech, problems with swallowing, paresis and fasciculations of the tongue appear. Weakness in the neck muscles is manifested by drooping of the head;
• simultaneous damage to central and peripheral motor neurons. In the arms there are simultaneously atrophies and increased reflexes with pathological signs of the hand, in the legs there are increased reflexes, decreased strength, and pathological foot symptoms in the absence of atrophies. Later, the bulbar region is affected.

CM. SEE ALSO: Amyotrophic lateral sclerosis: causes and mechanism of development

Bulbar form

In this form of the disease, the first symptoms of damage to the peripheral motor neuron in the brain stem are articulation disorders, choking when eating, nasal voice, atrophy and fasciculations of the tongue. Movement of the tongue is difficult. If the central motor neuron is also affected, then these symptoms are accompanied by an increase in the pharyngeal and mandibular reflexes, violent laughter and crying. The gag reflex increases.

As the disease progresses, paresis forms in the hands with atrophic changes, increased reflexes, increased tone and pathological foot signs. Similar changes occur in the legs, but somewhat later.

High form

This is a type of amyotrophic lateral sclerosis, when the disease occurs with primary damage to the central motor neuron. At the same time, paresis is formed in all muscles of the trunk and limbs with increased muscle tone and pathological symptoms.

With a high form, in addition to motor disorders, mental disorders appear: memory and thinking are impaired, intelligence indicators decrease. Sometimes these disorders reach the level of dementia (dementia), but this happens in 5% of all cases of amyotrophic lateral sclerosis.

Bulbar and high forms of ALS are prognostically unfavorable. Patients with this onset of the disease have a shorter life expectancy compared to the cervicothoracic and lumbosacral forms.

Whatever the first manifestations of the disease, it progresses steadily. Paresis in various limbs leads to impaired ability to move independently and take care of oneself. Involvement of the respiratory muscles in the process initially leads to the appearance of shortness of breath during physical activity, then shortness of breath becomes disturbing at rest, and episodes of acute lack of air appear. In the terminal stages, independent breathing is simply impossible; patients require constant artificial ventilation.

In rare cases, the final stages of the disease may include urinary disorders in the form of urinary retention or incontinence. With ALS, impotence develops quite early.

Due to impaired chewing and swallowing and muscle atrophy, patients lose a lot of weight. Muscle atrophy is detected by measuring the circumference of the limbs in symmetrical places. If the difference between the right and left sides is more than 1.5 cm, then this indicates the presence of atrophy. Pain syndrome in ALS is associated with joint stiffness due to paresis, prolonged immobility of the affected parts of the body, and cramps.

Since in ALS the tightness of the oral cavity is disrupted, the lower jaw and head hang down, this is accompanied by constant drooling, which is very unpleasant for the patient (especially considering that, in most cases, common sense and an adequate perception of one’s condition are maintained until the terminal stage of the disease ), gives the impression of a mentally ill person. This fact contributes to the formation of depression.

ALS is accompanied by autonomic disorders: increased sweating, greasy facial skin, changes in skin color, and limbs become cold to the touch.

According to various sources, the life expectancy of a patient with ALS ranges from 2 to 12 years, but more than 90% of patients die within 5 years of diagnosis. In the terminal stage of the disease, patients are completely bedridden, breathing is supported by a ventilator. The cause of death of such patients may be respiratory arrest, complications in the form of pneumonia, thromboembolism, infection of bedsores with generalization of infection.

Diagnostics

Differential diagnosis of amyotrophic lateral sclerosis involves the following studies:

1. MRI of the brain and spinal cord. It is carried out to exclude other pathologies of the brain substance.
2. Electromyography. It is carried out to confirm the presence of a denervation process (separation of nerve connections between muscles and the nervous system) and determine the degree of damage to the brain matter.
3. Biopsy of muscle tissue. Signs of muscle atrophy due to denervation are detected, often earlier than pathological changes are observed during electromyography.

To make a diagnosis, the following conditions are necessary: ​​the presence of signs of degenerative changes in motor neurons, the spread of the pathological process, the absence of other pathologies with identical symptoms. Spirography (measurement of speed and volume parameters of breathing) and polysomnography (sleep study) are carried out to determine the degree of dysfunction of the respiratory system.

Symptoms

Symptoms of amyotrophic lateral sclerosis are very specific, even with a basic initial examination. To clarify the clinical signs of the development of Charcot's disease, you need to have an accurate understanding of the motor neurons located in the central brain and on the periphery.

The central neuron is located inside the cerebral hemispheres. When it is damaged, weakness of the muscle tissue in the body occurs, which is combined with increased muscle tone and increased reflexes. Strengthening of reflexes is established during examination by a neurologist by blows with a hammer.

The location of the peripheral neuron is the brain stem and also the spinal cord. This pathology is also accompanied by a decrease in reflexes and muscle activity.

You should also take into account symptoms that signal disturbances in a system such as the vertebrobasilar system. Insufficiency in the VBB is observed due to decreased blood circulation in the arteries along the spine. This deviation is called vertebrobasilar insufficiency. And these pathologies develop in amyotrophic lateral sclerosis as symptoms.

Treatment methods

An effective treatment protocol for ALS has not been developed. A confirmed diagnosis predicts death for the patient. Drugs that can prolong a patient’s life: Riluzole and its analog Rilutek. The action of the drugs is based on inhibition of the process of release of an excitatory amino acid, the excess of which leads to degenerative damage to neurons. As a result of therapy, the life expectancy of patients increases by an average of 3 months.

Lateral sclerosis cannot be cured. The provision of palliative (supportive) medical care aimed at improving the patient’s quality of life is of decisive importance. Palliative treatment involves timely identification of problems and implementation of adequate treatment measures, provision of moral support and assistance in psychosocial adaptation. Palliative treatment of amyotrophic lateral sclerosis is carried out in the following areas:

• To reduce cramp syndrome (periodic cramps in the calf muscles) and fasciculations, the drugs Carbamazepine (first choice), magnesium-based drugs, Verapamil are indicated.
• To normalize muscle tone, muscle relaxants (Mydocalm, Baclofen, Tizanidine) are used. To reduce muscle spasticity, physical therapy and water procedures in the pool (water temperature 34°C) are prescribed in parallel with drug therapy.
• To correct dysarthria of spastic origin, medications are prescribed that reduce muscle tone. Non-drug treatments include applying ice cubes to the tongue area. When communicating with a patient, it is recommended to use simple speech structures that require primitive, laconic answers.

Treatment of ALS is carried out taking into account the dominant symptoms of the disease. With dysphagia, the patient has difficulty swallowing saliva, which causes involuntary drooling. Patients undergo regular oral sanitation. It is recommended to limit the consumption of fermented milk products, which contribute to the thickening of saliva.

If there are indications (significant reduction in body weight), an operation (endoscopic gastrostomy) is performed to create an artificial entrance to the stomach cavity at the level of the abdominal cavity to organize feeding. If walking is impaired, medical devices are used - strollers, walkers. Antidepressant therapy (Amitriptyline, Fluoxetine) is prescribed for the development of depressive states and emotional lability (sudden mood swings).

Mucolytic (Acetylcysteine) and bronchodilator agents are used to clean the trachea and branches of the bronchi. If respiratory function is significantly impaired, the patient is connected to a ventilator for artificial ventilation of the respiratory system. If indicated, an operation (tracheostomy) is performed to create an artificial anastomosis between the tracheal cavity and the environment.

Promising treatments include cell technologies that use stem cells to replace damaged cells and tissues in the body. The technique is used in practice to treat another disease caused by neuronal degeneration – multiple sclerosis.

Classification

BAS has the following forms:

• lumbosacral sclerosis;
• cervicothoracic disease;
• bulbar, which is a lesion of a peripheral neuron in the brain stem;
• affecting the central motor neuron.

At the same time, doctors distinguish between types of disease based on the speed of its progression and the strength of the symptoms manifested. The Mariana type of ALS is different in that the first signs appear early, but the disease progresses slowly. Classic (sporadic) is usually diagnosed in 95% of all patients. It is distinguished by an average rate of development of sclerosis and standard classical symptoms. Familial ALS is characterized by late onset and a hereditary pattern.

This division is based on determining the signs of damage to any neuron at the very beginning of the development of the disease. As pathological disorders progress, an increasing number of motor neurons become involved.

Common signs characteristic of any form of ALS are:

• dysfunction of the movement organs;
• absence of disturbances in the sensory organs;
• no problems with urination or defecation;
• progression of the disease and the capture of more and more areas of muscle tissue, sometimes to the point of complete immobility;
• periodic convulsions accompanied by severe pain.

Lumbosacral ALS

The lumbosacral disease ALS has two types of development:

1. The pathology begins to develop with damage to the peripheral neuron, which is localized in the lumbosacral region of the back brain. In this case, the patient shows signs of muscle weakness in one leg. Then the same symptoms appear in the muscles of the second, a decrease in tendon reflexes and tone in the muscle tissue of the legs is felt. Over time, signs of their “drying out” and twitching are observed. After some time, the muscle tissue of the arms is affected, which is manifested by a similar decrease in reflexes and atrophy. The next stage is damage to the bulbar group of neurons, which is expressed by deterioration of swallowing and blurred speech, nasality when speaking. Then the lower jaw sag and the chewing process worsens. At the same time, signs of fasciculation appear on the tongue.
2. In the initial stage of development of the disease, symptoms of damage to both motor neurons, which provide the ability to move the legs, can be traced. However, manifestations of muscle weakness in the legs are accompanied by their increased tone during atrophy and increased reflexes. After some time, abnormalities are detected first in the feet, and then in the hands. As the disease progresses, the swallowing process deteriorates, the tongue twitches, and speech is impaired. The patient often laughs or cries unnaturally.

Cervicothoracic ALS

It can proceed in two ways:

1. Damage to only a peripheral neuron, in which paresis and tissue atrophy are observed, first of one hand. After a month or two, the same symptoms appear in the tissues of the second. The hands become like a monkey's paw. Then the same symptoms are observed in the legs and other signs of the disease.
2. If simultaneous motor neuron lesions occur, both arms undergo atrophy at the same time, followed by the onset of other signs at an accelerated rate.

Bulbar type

With this form of ALS, symptoms of damage to a peripheral neuron in the brain stem begin to manifest themselves as impaired articulation, tickling while eating, nasal sound, and atrophy of the tongue muscles. As the disease progresses, the symptoms become more and more intense.

High type

This amyotrophic lateral sclerosis occurs with damage to the central neuron. At the same time, in addition to dysfunction of movements, mental disorders appear. They often manifest themselves in dementia, memory loss, etc. This form of the disease is the most dangerous.

Forecast

A diagnosis of ALS is a death sentence for the patient because the disease is considered incurable. Poor prognostic factors:

• Early debut.
• Male gender.
• A short period from the appearance of the first signs to confirmation of the diagnosis.

Usually in these cases the disease progresses quickly. The prognosis depends on the prevalence of the pathological process, the severity of symptoms, and the rate of progression of disorders.

ALS is an incurable disease associated with damage to motor neurons. It is characterized by a variety of clinical variants, which differ in the age of onset, variability in the localization of the primary lesion, and heterogeneity of clinical manifestations. Treatment is palliative.

Treatment

There is no cure for ALS, but it is possible to slow down the progression of this disease, increase life expectancy and alleviate a person’s condition.

For this purpose complex therapy is used:

Rilutek is a drug that was first used for the treatment of ALS in the UK and the USA. Active substances block the release of glutamine and slow down the process of neuronal damage. The drug must be taken 2 times a day, 0.05 g.

Muscle relaxants and antibiotics help treat muscle weakness. To eliminate muscle spasms and twitching, Mydocalm, Baclofen, and Sirdalud are prescribed.

To increase muscle mass, the anabolic steroid “Retabolin” is used.

Antibiotics if sepsis develops or infectious complications occur. Doctors prescribe fluoroquinolones, cephalosporins, carbopenes.

Vitamins B, E, A, C to improve the impulse along nerve fibers.

Anticholinesterase drugs that slow down the process of destruction of acetylcholine (“Kalimin”, “Prozerin”, “Pyridostigmine”).

In some cases, a stem cell transplant . It prevents the death of nerve cells, promotes the growth of nerve fibers and restores neural connections.

In the later stages, antidepressants and tranquilizers , non-steroidal painkillers and opiates are used.

If sleep is disturbed, benzodiazepine drugs are prescribed.

To facilitate movements, chairs and beds with various functions, canes, and fixing collars are needed. Doctors recommend speech therapy. In the later stages of the disease, a saliva ejector will be needed, and then a tracheostomy so that the patient can breathe.

Non-traditional treatment methods for ALS do not produce positive results.

Case history: amyotrophic lateral sclerosis

In the history of medicine, many, many diseases are named after great people. But with almost one hundred percent probability, when we hear “disease X” or “syndrome Y,” we can be sure that X and Y are the doctors who described the diseases. Sometimes the priority of one or another aesculapius is difficult to establish, and diseases with two or three names appear. Charcot-Marie-Tooth disease, for example. However, the disease that will be discussed in this chapter received not only the name of a doctor, but also a famous patient who became an icon both for all fans of American baseball and for patients. Moreover, it did a lot to popularize science, in particular, space and astrophysics thanks to the personality of another unique patient who died the day before yesterday, having lived 55 years with an illness that gave him only two years to live. We think you have already guessed that we will talk about amyotrophic lateral sclerosis, or Charcot's disease, or Lou Gehrig's disease. We dedicate this article to the memory of Stephen Hawking, who for many decades was a symbol of hope for patients with this terrible disease.

Stephen Hawking. Credit: Wikimedia Commons

Amyotrophic lateral sclerosis belongs to the group of motor neuron diseases, that is, it affects those nerve cells that are responsible for motor impulses coming down from the cortex to the muscles. The peculiarity of ALS is that the lesion covers all signal levels: both the upper motor neuron (those neurons that begin in the motor zone of the cerebral cortex) and the lower motor neuron (neurons at a lower level, the body of which is located in the anterior horns of the spinal cord and motor nuclei cranial nerves).

If we talk about the prevalence of the disease, then we can calm down a little: it does not occur very often - 3-5 cases per 100,000 people - with an incidence of 2.7 people per 100,000 per year. The age of those affected most often ranges from 55 to 65 years, but this group can include both very young people and long-livers. The famous Lou Gehrig's pathology appeared at the age of 36, but, apparently, it developed extremely quickly - he died a little short of his 38th birthday.

As a rule, people with an established diagnosis live from 2 to 5 years, but history still knows a couple of cases when the disease “stopped.” This is, of course, Stephen Hawking, who managed to live (and how to live!) with the disease for more than half a century, and guitarist Jason Becker, who has been living with Charcot's disease for almost 30 years.

A surgeon with the hands of an artist and the thoughts of a scientist

It is interesting that, with all due respect to Jean-Martin Charcot, pathology was first described by him, alas. Back in 1824, the outstanding Scottish anatomist, surgeon, philosopher and theologian Charles Bell outlined the symptoms of a disease in which a person first lost the strength of his arms and legs, then gradually lost control of his limbs, stopped speaking and breathing...

Charles Bell

It is interesting that Bell acquired such versatility of views at the university, where he went to study as a doctor in the footsteps of his older brother John Bell only because the rest attracted him little. During his studies, he once attended lectures by the most famous adept of the Scottish Enlightenment at that time, the philosopher and mathematician Dugald Stewart, who spoke about spiritual philosophy. Echoes of this knowledge were subsequently reflected in many of his works. Additionally, he also took a course in fine arts and learned to illustrate his works quite well, which was very useful to him in life.

After graduating from university in 1798, Bell assisted his brother in operations, being with him in the equivalent of a modern residency - the Edinburgh College of Surgeons, and subsequently helped to complete and illustrate volumes 3 and 4 of the four-volume Anatomy of the Human Body. Moreover, by that time he had already published his personal collection of drawings “Dissection System” according to the rules of anatomical dissection of the human body (all this happened in just 5 years of “residency”).

The discovery of amyotrophic lateral sclerosis could have been directly involved in Edinburgh, if not for Brother Bell's unfortunate quarrel with two teachers at the University of Edinburgh: Alexander Monro Secondus and John Gregory. The latter served as chairman of the Edinburgh Royal Infirmary and stated that only six full-time surgeons would be appointed to work at the hospital. The Bella brothers, of course, were not included in this number and, thus, lost the opportunity to practice there.

Charles Bell, who was not directly involved in the quarrel, did try to make a deal with the medical faculty. He offered the university one hundred guineas and his anatomy museum, which at that time was already filled with exhibits - wax preparations and drawings (they can still be seen in the Surgeons' Hall museum in Edinburgh), in exchange for being allowed to observe and do outlines of completed operations. However, the offer was not accepted.

This was followed by a move to London, practice, gaining experience, scientific work, membership in various “elite” surgical societies, as well as an undisguised interest in neurology. By the way, Bell, being a military surgeon, documented in detail the neurological injuries and lesions suffered by soldiers at the Battle of Waterloo (despite the fact that his surgical skills, to put it mildly, left much to be desired and were heavily criticized by other surgeons). But the drawings turned out excellent.

His interest went further, and already in 1811 he published the book “The Idea of ​​a New Anatomy of the Brain,” which presented the idea that there are different nerve pathways that go to different areas of the brain and, thereby, provide a variety of functions. Bell supported these assertions with flayer experiments with rabbits, to which the public for the protection of animal rights would now react much more sharply than to a dachshund placed under water, demonstrating the properties of a new liquid for breathing under water (the incident occurred in December 2019, when Deputy Prime Minister Dmitry Rogozin presented this achievement of domestic science to Serbian President Aleksandar Vucic - author's note).

The dachshund remained alive and unharmed, but the rabbits’ brains were cut and various nerve fibers were irritated, which led to various consequences - twitching of the paws, whiskers, nose, and so on. It was then that he discovered something that later helped him identify amyotrophic lateral sclerosis and led to a new round of evolution in neurology - the difference in the functions of the anterior and posterior horns of the brain. Irritation of the anterior horns led to all sorts of movements and muscle spasms, while the posterior horns seemed to have no effect on anything. A little later, it turned out that the dorsal horns contain sensitivity pathways that deliver signals from numerous receptors in the human body to the area of ​​the cerebral cortex that processes them.

In the 1821 work that made him famous, “On Nerves: An Account of Some Experiments on Their Structure and Functions, Which Lead to a New Arrangement of the System,” Bell substantiated that the facial nerve (7th pair of craniofacial nerves) is responsible for the movements of the facial muscles and turned the consciousness of surgeons, who at that time often tried to treat neuralgia by cutting it. This, naturally, led to unilateral paralysis of the facial muscles, which was called Bell's palsy in honor of the important discovery.

Neurological "Middle Ages" and "Renaissance"

But the disease still did not receive the name Bella. In 1850, another attempt to describe the disease was made by the English neurophysiologist Augustus Weller (or Waller). He became known to the world for the Wallerian degeneration named after him, in which a section of the axon, severed from the main neuron, is destroyed, and in its place Schwann cells (a type of glial cell characteristic of the peripheral nervous system) are formed, forming a “tunnel” around it. If the slices are aligned correctly, the axon end from the neuron body grows along the Schwann cells and can eventually reconnect with the innervated region. If not, then it thickens and can turn into a “painful” neuroma.

August Waller

But still, Jean-Martin Charcot played the main role in this issue. It was he who, in his 1874 work, was able to connect the symptoms of a gradual loss of motor activity with neuroanatomical problems: the loss of motor neurons. It was then, with his light hand, that the modern term first appeared: amyotrophic lateral sclerosis or ALS (in the English-speaking world - ALS, amyotrophic lateral sclerosis).

To mentally grasp the scale of Charcot's contribution, one needs to delve a little into the clinical state of affairs of those times, primarily from 1850 to 1874. Clinical diagnosis was still in its infancy. There was no distinction between upper and lower motor neurons, and no understanding of the role of the corticospinal tract in their connection (the pathway that enables movement). Some guesses have just emerged about how valuable tendon reflexes are in diagnostics. At the “lower end” of the motor pathway, it was generally not possible to separate different diseases, which manifest themselves mainly as weakness of the limbs.

Charcot's lecture at the Salpêtrière Hospital

Cases reported in the 1850s, for example by François Haran, modestly referred to "progressive spinal muscular atrophy", but there was no autopsy of these patients as evidence, nor any clinical distinction between neurogenic "nerves) or myopathic (“muscles hurt”) nature of the disease. Now there is the term “Arand-Duchenne amyotrophy,” but the name is only double because Guillaume Duchenne, after Arand, went through all his patients with electrodes and at least somehow quantitatively indicated the loss of function, after which he declared at one of the meetings of the French Academy of Sciences, which is entitled to priority. The Academy resolved the matter with a compromise.

Charcot compared all the work available at that time with his observations of the pathology of the anterior horn of the spinal cord in childhood spinal muscular atrophy, poliomyelitis and other disorders where muscle weakness occurs. He noticed that the problem sometimes lies not only “in front”, but also “to the side” - in the lateral horn. Helping to understand this was a woman with contractures (severe muscle spasms that change the appearance of a limb), which were considered “hysterical”, but in fact, as an autopsy showed, were early examples of primary lateral sclerosis.

As a result, Charcot combined all the observations and described “two cases of progressive spinal muscular atrophy with lesions of the gray matter and anterolateral bundles of the spinal cord.”

“We encountered several patients with the following conditions: paralysis with spasms of the arms and mainly legs (without loss of sensation) together with progressive amyotrophy, which was limited mainly to the upper limbs and trunk. ... The symptoms of progressive muscle atrophy developed sequentially. In the final stages of the disease, symptoms of paralysis and spasticity developed, which seemed to be associated with symmetrical sclerosis,” Charcot wrote.

By this time, the clinical researcher-clinician had already clearly associated clinical amyotrophy with the pathology of the anterior horns or motor neurons of the cranial nerves, which was detected at autopsy. And the apogee of this was the work “Amyotrophic lateral sclerosis” with such a detailed description of the clinical picture that it has not changed significantly to this day, although more than 140 years have passed (and he observed only 5 of his own patients and studied the stories of 15 people described by other doctors ).

“Currently the forecast is a grave,” concluded Charcot. “As far as I know, there is not a single case where, after all the observed symptoms, there was a subsequent cure. Is this an absolute obstacle? Only the future will tell."

The Greatest Tragedy in Baseball History

Gradually, scientific work accumulated, and the picture of the disease acquired new details. However, there was no system to all this. The talented American baseball player Lou Gehrig changed the situation and forced scientists to pay attention to the problem.

On the Fourth of July 1939, a 36-year-old man stood on the field of the famous Yankees baseball team and said: “Today I still consider myself the luckiest man on earth.” On that day, one of the greatest athletes in history officially said goodbye to his career and, in fact, to his life, since after that he had only a year and a half of continuous decline left to him.

It would seem that everything was going like clockwork: a good school, a decent university, a sports career like the launch of a jet plane, and already at the age of 20 - a contract with the strongest baseball team. Lou Gehrig's nickname became "the iron horse." And this is not surprising: he played 2,130 games in a row.

Everything was fine until 1938. If in 1937 Lou Gehrig was still shining on the winner's podium, then in 1938 there was already a rather strong decline in performance, and in the World Baseball League, which the Yankees won, he was almost invisible. At first it seemed like it was just aging. Or the fatigue that had accumulated over a decade and a half... In April 1939, it became clear that something was wrong with Lou. This month, by all measures, was the worst of his career.

As the days passed, Gehrig lost and lost strength. At the end of May he was already having difficulty walking. His wife Eleanor called the famous Mayo Clinic. When the person on the other end of the line realized whose wife was calling, the call was immediately transferred to surgeon Charles William Mayo, a member of the clinic’s board and the son of the co-founder. Mayo demanded that Lou be brought as soon as possible. On June 13, 1939, the famous baseball player arrived at the clinic. Six days of intensive examination brought a terrible gift to the athlete on his 36th birthday: a diagnosis of amyotrophic lateral sclerosis.

Lou Gehrig

Alas, although the doctors set the patient up for another 10-15 years of life, Lou Gehrig did not live even two. He died on June 2 at 10:10 pm in his home. On the day of the funeral, it seemed like the whole of New York came to say goodbye to him. And then hundreds of scientists around the world began to decipher the mysterious pathogenesis of the disease that so quickly brought one of the best athletes to the grave. And it was decided to immortalize his name in the title.

Another “icon” of the disease was the famous theoretical physicist and popularizer of science Stephen Hawking. The first signs of amyotrophic lateral sclerosis appeared in him at the age of 18-19 years, and at 21 the diagnosis was already clear. However, unlike Lu, sclerosis progressed extremely “reluctantly”, putting Hawking in a wheelchair only after 7 years.

In 2012, this unique person celebrated his 70th birthday and still continues to lead an active lifestyle and conduct scientific research, although he retains the ability to move only the facial muscle of the cheek, opposite which a motion sensor is mounted, which allows using a computer built into a wheelchair , communicate with the world.

What does modern science say?

At the moment, the scientific community has not reached a consensus as to why the disease begins to develop. We learned a lot: for example, that in the gene under the incomprehensible name C9orf72, a lot of four-stranded DNA suddenly appears (normally two helices), which disrupts transcription (translation of hereditary information into the “language” of RNA), and, accordingly, translation-synthesis squirrel. Hereditary forms of amyotrophic lateral sclerosis have also been discovered, which, however, account for only 5% of all cases encountered. But now it is known that the problems here are caused by a mutation in the superoxide dismutase-1 gene, located on the 21st chromosome.

In addition, we roughly determined the pathogenesis and found that due to too much glutamic acid (a neurotransmitter), neurons become overexcited and die. Moreover, there is evidence that in the early stages of the disease this is even good - that is, an increase in the excitability of healthy neurons compensates for the “strength” of the dead. But then the excitation increases with the increase in glutamic acid, and the pathological circle closes: the body begins to harm itself, and so-called excitotoxicity awakens.

Some cases associated with the random, in other words, sporadic manifestation of the disease, are combined with mutations in the TARDBP gene, due to which the TDP-43 protein appears outside the nucleus in the cytoplasm (usually it is located in the nucleus) and, like a pop star on the subway, begins to gather a crowd of other proteins around itself, interfering with normal intracellular movement. In addition, the products of the FUS gene or the Fusion in Sarcoma gene, which is also affected by a mutation, also have similar properties.

More recently, people have started talking about the therapeutic potential of autophagy, that is, the process by which a cell “eats” its own waste products, preventing them from accumulating inside itself, and converts them into fuel, which is again used for cellular needs. It was for the discovery back in 1993 of the genes responsible for such waste-free consumption that Japanese Yoshinori Ohsumi was awarded the Nobel Prize in Physiology or Medicine in 2019.

Neuroscientists from the Würzburg University Hospital have found that this very process of autophagy in motor neuron diseases, including ALS, simply breaks down. Naturally, also due to mutation. A breakdown occurs in the PLEKHG5 gene, due to which a lot of bubbles with this mediator accumulate in the synaptic endings, which transmit excitation to the muscle with the help of a neurotransmitter. In a normal cell, excess bubbles are disposed of, but the patient can no longer get rid of them. And in the end he dies.

We really don’t like writing this, but we haven’t yet come up with an effective treatment for amyotrophic lateral sclerosis. However, scientists around the world are fighting for this in the most active way - discovering new targets, testing new chemical compounds, creating new diagnostic methods that allow one to suspect the disease at an early stage, when one can still try to somehow help and slow down the process.

Even for research, money is collected, as they say, by the whole world - tens of thousands of people took part in the Ice Bucket Challenge flash mob, during which they poured a bucket of ice water over themselves. This made it possible to raise funds for the largest project in the history of disease research, “Genomic Translation for ALS Care,” which included more than 80 scientists from 11 countries and thanks to which they studied as much DNA as possible from sick patients ( this included about 1,500 people), discovering new damaged genes.

In the future, these genes may become targets for genetic therapy, which is gradually beginning to move out of the realm of pure science and into clinical use. Genetic modification methods, for example, have already been approved by the FDA in 2019 for the treatment of certain types of lymphoma and blindness.

There are also testable methods for genome editing in ALS. Thus, in December 2019, an article was published in the journal Science Advances where researchers from the University of California at Berkeley shared encouraging results in the treatment of Charcot disease, although so far only in mice and only with carriers of the mutant superoxide dismutase-1 gene. To do this, they took advantage of the recently discovered genome editing technology CRISPR/Cas9, discovered in bacteria. A specially trained virus delivered the Cas9 gene to glial cells adjacent to motor neurons, which “cut out” the harmful mutation.

The CRISPR/Cas9 technique also helped with the mutation of the FUS gene, successfully eliminating it from the cells. But various methods of pharmacological or genetic shutdown also combat the results of the activity of “bad” genes quite effectively.

There are already concrete successes in treating people. In May 2019, the drug Edaravone was announced, which in many years (no new drugs have appeared since 1995) became the first FDA-approved drug for the treatment of ALS. The edaravone molecule has antioxidant properties and reduces the amount of destructive free radicals in the cell, which prevents the development of oxidative stress and keeps neurons alive. But the price of the issue is still very high - an annual course of treatment in the USA costs about $150,000. But there is still a moderate positive effect.

Some more studies will just be launched. Scientists at Cedars-Sinai Hospital in Los Angeles have received FDA approval to conduct a clinical trial of a combination of gene therapy and stem cell therapy. Previously, the ALS Association certified this hospital as an advanced research center for finding a cure for Charcot's disease.

The second phase of the NurOwn study has also been completed. Innovative biotechnology company Brainstorm, which is focused on using stem cells to treat incurable diseases, announced the start of its third phase at the end of 2019. NurOwn is a cell therapy platform sourced from mesenchymal cells from the bone marrow of patients with ALS. Researchers endow mesenchymal cells with the ability to produce growth factors for neurons, which provide a kind of nutrition for the cells and have significant protective potential. Let's see what comes of this.

Neurochat at work

In the meantime, to interact with the world, immobilized patients can use the Russian development - the Neurochat program, which is created on the basis of a brain-computer interface and is designed for typing and exchanging messages via the Internet using the power of thought. The Neurochat terminal is a wireless headset with electrodes that is placed on the patient’s head and connected to a computer. The system, based on EEG signals, allows the patient to mentally select characters from a virtual keyboard and then send it to the recipient. Of course, the speed of such printing is low - only 5-6 characters per minute, but for a person completely deprived of the ability to speak, this is priceless.

Text: Anna Horuzhaya

Charles Bell. On the nerves; giving an account of some experiments on their structure and functions, which lead to a new arrangement of the system. Esq. Phil. Trans. R. Soc. Lond. 1821 111, 398-424.

Waller A. _ Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibers. Philos. Trans. R. Soc. London 1850, 140:423-29.

Charcot JM. De la sclerose laterale amyotrophique. Prog Med. 1874;2:325-327, 341-342, 453-455.

Charcot JM, Joffroy A. Deuxcas d'atrophie musculaire progressive avec lesions de la substance grise et de faisceaux anterolateraux de la moelle epiniere. Arch Physiol Norm Pathol. 1869;1:354-357; 2:628-649; 3:744-757.

Lewis P. Rowland. How Amyotrophic Lateral Sclerosis Got Its Name. The Clinical-Pathologic Genius of Jean-Martin Charcot. Arch Neurol. 2001;58(3):512-515.

Thomas Gaj, David S. Ojala, Freja K. Ekman, Leah C. Byrne, Prajit Limsirichai and David V. Schaffer In vivo genome editing improves motor function and extends survival in a mouse model of ALS. Science Advances, 2019. doi:10.1126/sciadv.aar3952

Wenting Guo, Ludo Van Den Bosch et al. HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients. Nature Communications, 2019. doi:10.1038/s41467-017-00911-y

Symptoms and complaints of patients

ALS begins with damage to the limbs, which later spreads to other parts of the body. The initial weakening of the muscles quickly increases, eventually leading to paralysis. The bladder sphincter and eye muscles are not affected.

Early stage symptoms:

• weakness and atrophy of the hands, impaired motor skills;
• muscle weakness in the feet and ankles;
• foot drop;
• muscle twitching, spasms of shoulders, arms, tongue;
• speech impairment and difficulty swallowing.

As the disease progresses, patients experience attacks of spontaneous crying or laughter, imbalance, and tongue atrophy.

It is believed that higher mental activity is not affected by ALS. However, in approximately 1-2% of episodes, cognitive function is impaired (even before normal symptoms appear) and dementia develops.

In later stages appear:

• depression;
• loss of ability to move;
• interruptions in breathing.

The disease is characterized by asymmetry of symptoms.

Treatment of ALS

There are no therapeutic methods that can cure ALS - treatment is aimed at prolonging the life of patients and improving its quality. The only drug that can slow down the development of the pathological process and delay death is the drug Rilutek. It is mandatory prescribed to people with this diagnosis, but in general it has virtually no effect on the patient’s condition.

"Rilutek"

For painful muscle spasms, muscle relaxants and anticonvulsants are prescribed; for the development of intense pain, strong analgesics, including narcotics. Patients with amyotrophic lateral sclerosis often experience emotional instability (sudden, unreasonable laughter or crying), as well as manifestations of depression; psychotropic drugs and antidepressants are prescribed to eliminate these symptoms.

Pharmacological effects of muscle relaxants

To improve muscle condition and motor activity, therapeutic exercises and orthopedic devices are used, including cervical collars, splints, and devices for grasping objects. Over time, patients lose the ability to move independently, as a result of which they have to use wheelchairs, special lifts, and ceiling systems.

HAL therapy. Used in clinics in Germany and Japan. Allows you to improve the patient's mobility. The treatment method slows down muscle atrophy, but does not affect the rate of death of motor neurons and the patient’s life expectancy. HAL therapy involves the use of a robotic suit. It takes signals from nerves and amplifies them, causing muscles to contract. In such a suit a person can walk and perform all the necessary actions for self-care

Wheelchairs for disabled people

As the pathology develops, patients' swallowing function is impaired, which interferes with normal food intake and leads to a deficiency of nutrients, exhaustion and dehydration. To prevent these disorders, patients are given a gastrostomy tube or a special probe is inserted through the nasal passage. As a result of weakening of the muscles of the pharynx, patients stop talking, and they are recommended to use electronic communicators to communicate with others.

Installed gastrostomy tube

In the last stages of ALS, patients' diaphragm muscles atrophy, which makes breathing difficult, not enough air gets into the blood, shortness of breath, constant fatigue, and restless sleep are observed. At these stages, a person, if there are appropriate indications, may need non-invasive ventilation using a special device with a mask connected to it.

If you want to find out in more detail the diagnosis of ALS - what it is, you can read an article about it on our portal.

Good results in eliminating the symptoms of amyotrophic lateral sclerosis are provided by massage, aromatherapy and acupuncture, which promote muscle relaxation, blood and lymph circulation, and reduce anxiety and depression.

Acupuncture

An experimental method of treating ALS is the use of growth hormone and stem cells, but this area of ​​medicine has not yet been fully studied, so it is not yet possible to talk about any positive results.

Important: the condition of people suffering from amyotrophic lateral sclerosis largely depends on the care and support of loved ones - patients require expensive equipment and round-the-clock care.

Support from loved ones is very important

Lifts for the disabled

Development of the disease

What else is important for people interested in ALS (disease) to know? The symptoms that appear in a patient as the disease progresses can indicate what type of disease he has:

1. ALS of the extremities. The legs are affected first. Further impairment of the functionality of the limbs progresses.
2. Bulbar ALS. In this case, the main symptoms are impaired speech function, as well as problems with swallowing. It is worth saying that this type of disease occurs much less frequently than the first.

Clinical picture

Symptoms of amyotrophic lateral sclerosis vary depending on the level of damage:

1. With pathology in the cervical and thoracic spinal cord, the first symptoms will be the development of flaccid paralysis of the upper limbs. In this case, an increase in all reflexes will be observed. Then signs of tense paralysis of the lower extremities appear, and all reflexes also intensify.
2. Pathological signs of damage to the pyramidal tracts appear . Muscle atrophy gradually develops. The progression of the disease leads to impaired mobility of the diaphragm and intercostal muscles - as a result, acute respiratory failure develops.
3. If the disease begins with damage to the lumbar and cruciate regions, the first to develop is flaccid paralysis of the lower extremities and increased reflexes. Pathological pyramidal symptoms are added.
4. Then tension paralysis of the upper limbs with hyperreflexia is formed. Upper limb paralysis reaches its maximum later than lower limb paralysis. In both cases, the last stage is signs of bulbar insufficiency.

There is a bulbar form - with it the disease begins with the following symptoms:

• impairment ;
• The voice becomes nasal;
• develops , as a result of which the swallowing process is disrupted;
• After this, paresis of the soft palate appears, reflexes intensify, and signs of oral automatism appear;
• Gradually, paralysis affects the upper and then lower limbs;
• In this case, enhanced reflexes and pyramidal signs are observed;
• This form of the disease is accompanied by a sharp decrease in body weight due to difficulties with eating;
• At the last stage, respiratory failure develops.

The most unfavorable variant of the development of amyotrophic lateral sclerosis is the primary generalized form:

• Paralysis of all limbs immediately
• Tendon reflexes are weakened;
• Almost immediately, bulbar syndrome appears with impaired speech and swallowing;
• The patient quickly loses body weight;
• Respiratory failure develops quickly

Etiology

The exact etiology of ALS is unknown. In approximately 5% of cases, familial (hereditary) forms of the disease occur. 20% of familial cases of ALS are associated with mutations in the superoxide dismutase-1 gene, located on chromosome 21[2][3]. This defect is believed to be inherited in an autosomal dominant manner.

Increased activity of the glutamatergic system plays a key role in the pathogenesis of the disease, while excess glutamic acid causes overexcitation and death of neurons (so-called excitotoxicity). The remaining motor neurons may spontaneously depolarize, which is clinically detected by fasciculations.

Scientists from Johns Hopkins University in Baltimore have identified the molecular genetic mechanism underlying the occurrence of this disease. It is associated with the appearance in cells of a large amount of four-stranded DNA and RNA in the C9orf72 gene, which leads to disruption of the transcription process, and, consequently, protein synthesis. However, the question of how exactly these changes lead to the degradation of motor neurons remains open[4].

Also important in pathophysiology is TDP-43, which has been identified as a major component of ubiquitinated cytoplasmic protein aggregates in all patients with sporadic ALS, but located outside the nucleus (in normal neurons it is in the nucleus). Although the question of whether these aggregates cause neurodegeneration in ALS remains open, mutations in TARDBP were found in only 3% of cases of hereditary sclerosis and in 1.5% of patients with sporadic ALS, suggesting that the aggregates TDP-43 plays a key role in the initiation of ALS. In addition to mutations in the TARDBP gene, zinc ions can also cause TDP-43 aggregation.[5][6]

The discovery of mutations in the FUS (Fusion in Sarcoma) gene on chromosome 16, which are associated with hereditary forms of ALS, supports this theory. FUS aggregates were not clearly identified in patients with pathological alterations in TDP-43 or SOD1, suggesting a novel disease pathway.

Differential diagnosis

Since the symptoms of amyotrophic lateral sclerosis are similar in many ways to the manifestations of other neurological pathologies, doctors must carry out a differential diagnosis. The most accurate diagnosis can be made using MRI of the brain and spine. First of all, ALS must be differentiated from muscle diseases, which include Rossolimo-Steinert-Kurshman dystrophic myotonia, myositis with cellular abnormalities, and oculopharyngeal myodystrophy.

It is also necessary to distinguish ALS from spinal cord pathologies:

• chronic vertebrogenic ischemic myelopathy;
• Kennedy bulbospinal amyotrophy;
• syringomyelia;
• tumors;
• familial spastic paraplegia;
• chronic lymphocytic leukemia;
• hexosaminidase deficiency;
• lymphoma.

Differential diagnosis is also necessary in order to distinguish the disease from systemic pathologies, lesions of the neuromuscular synapse, and brain pathologies such as multiple system atrophy, dyscirculatory encephalopathy, and syringobulbia.