Amyotrophic lateral sclerosis treatment. Skeletal motor units. The main causes of the disease

Lou Gehrig's disease, or amyotrophic lateral sclerosis, is a rapidly progressive pathology of the nervous system, which is characterized by damage to motor neurons in the spinal cord, brain stem and cortex. In addition, motor branches of cranial neurons (glossopharyngeal, facial, trigeminal) are involved in the pathological process.

Etiology of the disease

This disease is quite rare and occurs in two to five people per 100,000. It is believed that the disease develops more often in men after fifty years. Amyotrophic Lateral Sclerosis is no exception and affects people various professions(teachers, engineers, Nobel laureates, senators, actors) and various social status. The most famous patient diagnosed with amyotrophic lateral sclerosis was world baseball champion Lou Gehrig, who gave the disease an alternative name.

In Russia, Lou Gehrig's disease is also widespread. To date, there are about 15-20 thousand patients with this diagnosis. Among the most famous people in Russia with such a pathology, it is worth noting the composer Dmitry Shostakovich, the performer Vladimir Migulya, and the politician Yuri Gladkov.

Causes of Lou Gehrig's Disease

The basis of this disease is the accumulation of pathological insoluble protein in the motor cells of the nervous system, which leads to their death. The cause of this pathology has not yet been elucidated, but there are many theories. Among the main ones:

neural- British scientists suggest that the development of the disease is associated with glial elements, these are cells that ensure the vital activity of neurons. Numerous studies have shown that with a decrease in the functions of astrocytes, which remove glutamate from nerve endings, the likelihood of developing a formidable disease increases tenfold.

Gennaya- 20% of patients have abnormalities in the genes that encode the enzyme Superoxide dismutase-1. This enzyme is responsible for converting toxic nerve cells superoxides to oxygen.

autoimmune- the theory is based on the detection of specific antibodies in the blood, which begin to eliminate motor nerve cells. There are studies that prove the existence of such antibodies against the background of the presence of others. serious illnesses(for example, with Hodgkin's lymphoma or lung cancer).

hereditary- pathology is hereditary in 10% of cases.

Viral- the theory was especially popular in the 60-70s of the last century, but did not find confirmation in the future. Scientists from the USSR and the USA conducted experiments on monkeys by introducing extracts obtained from sick people into the spinal cord. Other researchers tried to prove the involvement of the polio virus in the formation of pathology.

Classification of amyotrophic lateral sclerosis:

Manifestations of Lou Gehrig's disease

Any of the forms of the disease begins in the same way: the patient complains of increasing muscle weakness, decreased muscle mass and the occurrence of fasciculations (muscle twitches).

The bulbar form of amyotrophic lateral sclerosis is characterized by damage to the cranial nerves (12, 10 and 9 pairs):

patients have impaired pronunciation and speech, it becomes difficult to move their tongue;

over time, the act of swallowing begins to be disturbed, the patient often chokes, food can shoot out through the passages of the nose;

patients feel involuntary twitches of the tongue;

progression of Lou Gehrig's disease is accompanied by the development complete atrophy muscles of the neck and face, facial expressions are completely lost, the patient cannot open his mouth, chew food.

The cervicothoracic variant of the disease affects the upper limbs, while the process develops symmetrically, on both sides:

at first, the patient feels a deterioration in the functions of the hands, writing becomes difficult, playing musical instruments, it becomes difficult to perform complex movements;

at the same time, there is a strong tension in the muscles of the hands, tendon reflexes increase;

over time, weakness begins to spread to the muscles of the shoulder and forearm, they atrophy, the upper limb resembles a dangling whip.

The lumbosacral form begins with a feeling of weakness lower extremities:

patients complain that it is difficult for them to climb stairs, walk long distances, stand on their feet, and perform daily work;

after a certain time, the foot begins to sag, atrophy of the muscles of the legs occurs, such patients are not able to stand on their feet;

pathological tendon reflexes (Babinsky) occur, patients begin to suffer from fecal and urinary incontinence.

Regardless of the variant of the disease in the initial stages of the disease, the outcome is the same for everyone. The disease is constantly progressing and spreads to all the muscles of the body, including even the muscles respiratory system. After their refusal, the patient must be transferred to artificial lung ventilation and provide constant care.

These patients usually die from developing concomitant diseases(sepsis, pneumonia). Even in the case of proper care, they begin to develop bedsores, hypostatic pneumonia. Realizing the completeness of the severity of their own disease, such patients often fall into apathy, depression, cease to be interested in their loved ones and the outside world.

Over time, the psyche of patients undergoes significant changes. So patients can show incontinence, aggressiveness, emotional lability, act up. Conducting intelligence tests shows a decrease in thinking and mental capacity, deterioration of attention and memory.

Diagnosis of amyotrophic lateral sclerosis

Among the main diagnostic methods are:

MRI of the head and spinal cord- the method is very informative and allows you to detect atrophy of the motor parts of the brain, as well as the degeneration of pyramidal structures.

Cerebrospinal puncture - an elevated or normal protein content is usually present.

Neurophysiological examinations - transcranial magnetic stimulation (TCMS), electromyography (EMG), electroneurography (ENG).

Molecular genetic analysis- study of the gene that is responsible for encoding Superoxide dismutase-1.

Biochemical blood test - reveals an increase in creatine phosphokinase (an enzyme that is formed during the breakdown of muscle tissue), a slight increase in liver enzymes (AST, ALT), the accumulation of toxins in the blood (creatinine, urea).

Due to the fact that amyotrophic lateral sclerosis has symptoms similar to other pathologies, it is necessary to conduct a differential diagnosis:

Lambert-Eaton syndrome, myasthenia gravis - diseases of the neuromuscular synapse;

peripheral nerve diseases: multifocal motor neuropathy, Isaacs neuromyotonia, Personage-Turner syndrome;

diseases of the spinal cord: lymphoma or lymphocytic leukemia, syringomyelia, spinal amyotrophy, tumors of the spinal cord;

systemic diseases;

muscle diseases: myotonia Rossolimo-Steinert-Kurshman, myositis, parapharyngeal myodystrophy;

brain diseases: dyscirculatory encephalopathy, multisystem atrophy, tumors cranial fossa(rear).

Treatment of Lou Gehrig's disease or amyotrophic lateral sclerosis

Any treatment for this disease given time is ineffective. Proper care of the patient, drugs can prolong the life of the patient, but do not provide recovery. Symptomatic therapy includes:

Rilutek (Riluzole) is a drug that has done well in the UK and the US. The principle of its action is to block glutamate in the brain, thereby improving the work of Superoxide dismutase-1.

RNA interference is a fairly promising method for treating this disease, the creators of which were awarded the Nobel Prize. The technique is based on blocking the synthesis of pathological protein in the nerve cells themselves, which prevents their subsequent death.

Stem cell transplantation - studies show that stem cell transplantation in the CNS prevents the death of nerve cells, improves the growth of nerve fibers and restores neural connections.

Muscle relaxants - eliminate twitching and muscle spasms (Sirdalud, Mydocalm, Baclofen).

Retabolil (Anabolics) - contribute to an increase in muscle mass.

Anticholinesterase drugs (Pyridostigmine, Kalimin, Prozerin) - prevent the rapid destruction of acetylcholine in the neuromuscular synapses.

Vitamins of group B (Neurovitan, Neurorubin), vitamins C, E, A - these drugs improve the conduction of nerve impulses along the fibers.

Broad-spectrum antibiotics (carbopenems, fluoroquinolones, 3-4 generation cephalosporins) are indicated in case of complications of an infectious nature, sepsis.

Complex therapy of the disease necessarily includes the use of a nasogastric tube for feeding, classes with a physical therapy doctor, massage, and psychological consultations.

Forecast

The prognosis in the presence of amyotrophic lateral sclerosis is unfavorable. The patient dies just a few months or years after the onset of the disease, the average life expectancy of such patients is:

with lumbar debut - 2.5 years;

with bulbar - 3-5 years;

only about 7% live more than five years.

The prognosis is more favorable with the hereditary nature of the disease, which is associated with mutations in the gene that encodes Superoxide dismutase-1.

The situation in Russia is overshadowed by the lack of proper care for patients, which may be evidenced by the fact that the drug Riluzot, which can significantly slow down the course of the disease, was not even registered in Russia until 2011, and the disease itself in the same year (catastrophic delay) was included in the list of rare pathologies. However, in Moscow there are:

Charity Fund for ALS Patients named after G. N. Levitsky;

fund for helping patients with Lou Gehrig's disease at the Marfo-Mariinsky Mercy Center.

In the end, I would like to note that such a formidable disease does not go unnoticed by the general public, namely, in July 2014, the Ice Bucket Challenge charity event was held. This action was aimed at raising funds to support patients with amyotrophic lateral sclerosis, the action turned out to be quite large-scale. In its course, the organizers managed to raise over forty million dollars for the needs of ALS patients.

The essence of this action was that a person either douses himself with ice water and shoots it on a video camera, or donates a certain amount of money for the needs of the organization. The action became especially popular due to the participation of well-known politicians, actors and performers.

The disease amyotrophic lateral sclerosis (ALS) occurs in three out of a hundred thousand people. Despite today's advances in medicine, the mortality rate from this pathology is 100%. However, there are cases when patients did not die over time, their condition stabilized. A prime example is the famous guitarist Jason Becker. He has been actively fighting this disease for more than 20 years.

What is BAS?

With this disease, there is a consistent death of the motor neurons of the spinal cord and individual parts of the brain, which are responsible for voluntary movements. Over time, the muscles in people with this diagnosis atrophy, as they are constantly inactive. The disease manifests itself in the form of paralysis of the limbs, muscles of the body and face.

Amyotrophic lateral sclerosis is called amyotrophic lateral sclerosis solely because the neurons that conduct impulses to all muscles are located on both sides of the spinal cord. The last stage of the disease is diagnosed when the pathological process reaches the respiratory tract. Death occurs due to muscle atrophy or infection. In some cases, the respiratory muscles are affected before the limbs. A person dies very quickly without experiencing all the hardships of life with paralysis.

In many European countries, amyotrophic lateral sclerosis is known as Lou Gehrig's disease. This famous baseball player from America was diagnosed back in 1939. In just a couple of years, he completely lost control over his body, his muscles were exhausted, and the athlete himself became disabled. Lou Gehrig passed away in 1941.

Risk factors

In 1865, Charcot (a French neurologist) first described this disease. Today, no more than five people out of a hundred thousand suffer from it all over the world. The age of patients with this diagnosis varies from 20 to 80 years. Representatives of the stronger sex are more susceptible to this disease.

In 10% of cases, ALS disease is inherited. Scientists have identified about 15 genes, the mutation of which manifests itself to varying degrees in people with this pathology.

The remaining 90% of cases are sporadic, that is, not related to heredity, in nature. Experts cannot name specific causes leading to the development of the disease. It is assumed that some factors may still increase the risk of the disease, namely:

• Smoking.
• Work in a hazardous industry.
• Service in the army (scientists find it difficult to explain this phenomenon).
• Eating foods that have been grown with pesticides.

The main causes of the disease

A severe pathological process can be triggered by completely different factors that we encounter daily in real life. Why does ALS occur? The reasons may be as follows:

• Intoxication of the body with heavy metals.
• Infectious diseases.
• Deficiency of certain vitamins.
• Electrical injury.
• Pregnancy.
• Malignant neoplasms.
• Surgical interventions (removal of part of the stomach).

Forms of the disease

The cervicothoracic form is characterized by the spread of the pathological process to the area of ​​the shoulder blades, arms and the entire shoulder girdle. It gradually becomes difficult for a person to perform habitual movements (for example, fasten buttons), on which he did not have to concentrate before the illness. When the hands stop "obeying", complete muscle atrophy occurs.

The lumbosacral form is characterized by damage to the lower extremities like hands. Gradually, weakness of the muscles in this area develops, twitches and convulsions appear. Patients begin to experience difficulty walking, constantly stumbling.

The bulbar form is one of the most severe manifestations diseases. Patients very rarely manage to live more than four years from the moment of onset primary symptoms. The signs of ALS disease begin with problems with speech and uncontrollable facial expressions. Patients have difficulty swallowing, which turns into a complete inability to eat independently. The pathological process, capturing the entire human body, negatively affects the work of the respiratory and cardiovascular systems. That is why patients with this form die before paralysis develops.

The cerebral form is characterized by simultaneous involvement in the pathological process of both the upper and lower extremities. In addition, patients may cry or laugh for no reason. By gravity cerebral form not inferior to the bulbar, so death from it comes just as quickly.

Clinical picture

According to some data, even at the preclinical stage, approximately 80% of motor neurons die. All their work is taken over by adjacent cells. They gradually increase the number of terminal branches, and the so-called ionic code begins to be translated to a large number of muscles. Due to the created overload, these neurons also die. This is how amyotrophic lateral sclerosis begins. Symptoms of the disease do not appear immediately after the death of motor neurons.

It may take 5-7 months before a person pays attention to the external changes in his body. Patients, as a rule, have a decrease in body weight and muscle weakness, there are difficulties with the implementation of daily activities. It becomes difficult to move normally, carry objects in your hands, breathe, swallow and speak. Convulsions and twitches appear. Such symptoms are characteristic of many diseases, which significantly complicates the diagnosis of ALS in the early stages of development.

With this pathology, the systems of internal organs (kidneys, liver, heart), muscles responsible for intestinal motility are never affected.

ALS disease is progressive in nature, and over time it captures more and more areas of the body. A person gradually loses the ability to move easily, due to a violation of swallowing reflexes, food constantly enters the respiratory tract, which causes interruptions in breathing. In the last stages, vital activity is supported only thanks to artificial nutrition and a ventilator.

Diagnostics

Diagnosis of the disease is extremely difficult. The thing is that in the initial stages, ALS disease has similar symptoms with others. neurological disorders. Only after a thorough examination of the patient, the doctor can make a final diagnosis.

Diagnosis implies a multifaceted study of the patient's health, starting with the collection of anamnesis and ending with molecular genetic analysis. In addition, a neurological examination, MRI, serological and biochemical blood tests are prescribed.

What should be the treatment?

At present, experts are unable to offer effective methods treatment. All assistance from doctors is reduced to facilitating the manifestations of the disease as much as possible.

Treatment of amyotrophic lateral sclerosis includes taking anticholinesterase drugs (Galantamine, Prozerin) to improve the quality of speech and swallowing, muscle relaxants (Diazepam), antidepressants and tranquilizers. For infectious lesions, it is prescribed antibiotic therapy. In case of severe pain, doctors recommend taking non-steroidal anti-inflammatory drugs, which are subsequently replaced with narcotic drugs.

the only effective drug purposeful action is Rilutek. It not only prolongs the life of the patient, but also allows you to increase the delay in the transfer to the ventilator.

Good care significantly improves the quality of life

Of course, every person who has been diagnosed with ALS needs proper care. The patient critically examines his condition, because every day his body literally fades. Ultimately, such people cease to serve themselves independently, communicate with relatives and friends, and become depressed.

Without exception, all ALS patients need:

• In a functional bed with a special lifting mechanism.
• In the toilet seat.
• In a wheelchair with automatic control.
• In the means of communication, for example, in a laptop.

Nutrition of patients also requires special attention. It is better to give well-swallowed food, rich in vitamins and proteins. Subsequently, nutrition without the help of a special probe is not possible.

Amyotrophic lateral sclerosis develops rapidly in some people. Relatives and friends have a very hard time, because a person is literally fading away before our eyes. Often people who care for the sick need additional help from a psychologist, as well as taking sedatives.

Forecast

If the doctor confirmed amyotrophic lateral sclerosis, the symptoms only increase from day to day, the general condition of the patient worsens, the prognosis in this case is disappointing. In the entire history of modern medicine, only two cases have been recorded when patients managed to survive. We have already talked about the first in this article. And the second is the famous physicist Stephen Hawking, who has continued to successfully exist with such a disease for the last 50 years of his life. The scientist is actively working and enjoys every new day, although he moves around in a specially equipped chair, and communicates with others through a computer speech synthesizer.

Preventive measures

There is no need to talk about the primary prevention of pathology, since the exact causes of its occurrence are still not clear. Secondary prevention should be aimed at slowing the progression of the disease and prolonging the life of the patient. It includes:

1. Regular consultations with a neurologist and taking medications.
2. Complete rejection of all bad habits because they only exacerbate ALS disease.
3. Treatment should be adequate and competent.
4. Balanced and rational nutrition.

Conclusion

In this article, we talked about what constitutes ALS disease. Symptoms and treatment of such a pathological condition should not be ignored. Unfortunately, modern medicine can't offer effective therapy against this disease. However, relatives and friends should make every effort to improve the daily life of a person with such a diagnosis.

Let us discuss in detail such a disease as amyotrophic lateral sclerosis. Find out what it is, what are the symptoms and causes. Let's touch on the diagnosis and treatment of ALS disease. And also there will be many other useful recommendations on this topic.

is a neurodegenerative disease accompanied by the death of central and peripheral motor neurons. This leads to gradual atrophy of skeletal muscles, dysphagia, dysarthria, alimentary and respiratory failure. The disease progresses steadily and is accompanied by death.

This determines the relevance of studying the problem. It was first described by the French psychiatrist Jean-Martin Charcot in 1869. For which it received such a second name as Charcot's disease.

In the US and Canada, it is also known as Lou Gehrig's disease. For 17 years he was a top-notch American baseball player. But unfortunately, at the age of 36, he fell ill with amyotrophic lateral sclerosis. And the next year he passed away.

It is known that the majority of ALS patients are people with high intellectual and professional potential. They quickly become severely disabled and die.

The motor analyzer is affected. This is part of the nervous system. It transmits, collects and processes information from the receptors of the musculoskeletal system. It also organizes coordinated human movements.

If you look at the figure below, you will see that propulsion system very difficult to organize.

In the upper right corner we see the primary motor cortex, the pyramidal tract that goes to the spinal cord. It is these structures that are affected in ALS.

Anatomy of the pyramidal tract

Here is the anatomy of the pyramidal tract. Here you see an additional motor area, the premotor cortex.

These transformations transmit signals from the brain to the motor neurons of the spinal cord. They innervate skeletal muscles and regulate voluntary movements.

Amyotrophic Lateral Sclerosis is an unusual neurodegenerative disease! ICD code 10— G12.2.

All the worst with him happens when a person still does not feel anything. At this preclinical stage 50 - 80% of motor neurons die after a genetic failure is realized with the participation of environmental factors. Then, when 20% of resistant motor neurons remain, the disease itself begins.

The pathogenesis of amyotrophic lateral sclerosis

If we talk about the pathogenesis of amyotrophic lateral sclerosis, then first of all we must understand the following. There are various (largely unknown) genetic factors.

They are realized in conditions of selective vulnerability of motor neurons. That is, in those conditions that ensure the normal vital and physiological work of these cells.

However, under pathological conditions, they play a role in the development of degeneration. This subsequently leads to the main mechanisms of pathogenesis.

Motoneurons are the most large cells nervous system with long conducting processes ( up to 1 meter). They need high energy costs.

Each such motor neuron is a special power plant. She takes over great amount impulses and then transmits them to implement coordinated human movements.

These cells need a lot intracellular calcium. It is he who ensures the work of many motor neuron systems. Therefore, the production of proteins that bind calcium is reduced in cells.

The expression of certain glutamate receptors (ampa) and the expression of proteins (bcl-2) that prevent the programmed death of these cells is reduced.

Under pathological conditions, these features of the motor neuron work on the process of degeneration. As a result, there is:

• Toxicity (glutamate excitotoxicity) stimulating amino acids
• Oxidative (oxidative) stress
• Disruption of the cytoskeleton of motor neurons
• Degradation of proteins is disturbed with the formation of certain inclusions
• There is a cytotoxic effect of mutant proteins (sod-1)
• Apoptosis or programmed cell death of motor neurons

Types of disease

Family ALS(Fals) - occurs when the patient in the history of the family has similar cases of this disease. It makes up 15%.

In other cases, when they have more complex inheritance paths (85%), we are talking about sporadic ALS.

Epidemiology of motor neuron disease

If we talk about the epidemiology of motor neuron disease, then the number of new patients per year is somewhere around 2 cases per 100,000 people. The prevalence (the number of patients with ALS at the same time) ranges from 1 to 7 cases per 100,000 people.

As a rule, people from 20 to 80 years old get sick. Although exceptions are possible.

average life expectancy:

• if ALS disease begins with a speech disorder (with a bulbar debut), then they usually live 2.5 years
• if it starts with some kind of motor disorders (spinal debut), then it is 3.5 years

However, it should be noted that 7% of patients live longer than 5 years.

Genetic loci of familial ALS

Here we see many types of familial ALS. More than 20 mutations have been discovered. Some of them are rare. Some are common.

Genetic loci of familial ALS

There are also new ALS genes. We have not shown some of them. But the bottom line is that all these mutations lead to one final path. To the development of damage to the central and peripheral motor neurons.

Classification of motor neuron diseases

Below is a classification of motor neuron diseases.

Norris classification (1993):

• Amyotrophic lateral sclerosis - 88% of patients:
  • bulbar debut of ALS - 30%
  • chest debut - 5%
  • diffuse - 5%
  • cervical - 40%
  • lumbar - 10%
  • respiratory - less than 1%
• Progressive bulbar paralysis - 2%
• Progressive Muscular Atrophy - 8%
• Primary lateral sclerosis - 2%

Bass Variations by Hondkarian (1978):

1. Classic - 52% (when lesions of the central and peripheral motor neurons are evenly represented)
2. Segmental-nuclear - 32% (small signs of a central lesion)
3. Pyramidal - 16% (we see signs of a peripheral lesion not as bright as signs of a central one)

Natural pathomorphosis

If we talk about different debuts, then it should be noted that the sequence of development of symptoms is always certain.

At bulbar debut first there are speech disorders. Then swallowing problems. Then there is paresis in the limbs and respiratory disorders.

At cervical debut the process of violation begins with one hand and then passes to the other. After this, bulbar disturbances and movement disorders in the legs may occur. It all starts on the side on which the primary hand suffered.

If speak about thoracic debut of ALS, then the first symptom that patients usually do not notice is weakness of the back muscles. The state is broken. Then paresis occurs in the arm along with atrophy.

At lumbar debut one leg is affected first. Then the second is captured, after which the disease passes to the hands. Then there are respiratory and bulbar disorders.

Clinical manifestations of Charcot's disease

The clinical manifestations of Charcot's disease include:

1. Signs of damage to peripheral motor neurons
2. Signs of damage to the central motor neurons
3. Combination of bulbar and pseudobulbar syndromes

Fatal complications leading to death:

1. Dysphagia (impaired swallowing) and alimentary (nutritional) malnutrition
2. Spinal and stem respiratory disorders due to atrophy of the main and accessory respiratory muscles

Signs of damage to the central motor neuron

Signs of damage to the central motor neuron include:

1. Loss of dexterity - the disease begins with the fact that a person begins to have difficulty fastening buttons, tying shoelaces, playing the piano or threading a needle
2. Then muscle strength decreases
3. Increased spastic muscle tone
4. Hyperreflexia appears
5. Pathological reflexes
6. Pseudobulbar symptoms

Signs of damage to the peripheral motor neuron

Signs of damage to the peripheral motor neuron are combined with signs of damage to the central:

1. Fasciculations (visible twitches in the muscles)
2. Cramps (painful muscle cramps)
3. Paresis and atrophy of the skeletal muscles of the head, trunk and limbs
4. Muscle hypotension
5. Hyporeflexia

Constitutional symptoms of ALS

The constitutional symptoms of ALS include:

• ALS-associated cachexia(loss of more than 20% of body weight in 6 months) is a catabolic event in the body. It is associated with death. a large number cells of the nervous system. In this case, patients are prescribed anabolic hormones. Even cachexia can develop from malnutrition.
• Fatigue(restructuring of the end plates) - in a number of patients, a decrement of 15 - 30% is possible with EMG

Rare symptoms in amyotrophic lateral sclerosis

Here's what applies to rare symptoms in amyotrophic lateral sclerosis:

• Sensory disorders. However, it has been shown that in 20% of cases, ALS patients (especially in the elderly) have sensory impairments. This is polyneuropathy. In addition, if the disease begins with the hands, then the patient simply hangs them. They have impaired circulation. Potentials may decrease in these sensory nerves as well.
• Violation of oculomotor functions, urination and stool are extremely rare. Less than 1%. However, more frequent secondary disorders are possible. This is a weakness of the pelvic floor muscles.
• Dementia (dementia) occurs in 5% of cases.
• Cognitive impairment - 40%. In 25% of cases they are progressive.
• Bedsores - less than 1%. As a rule, they occur with severe alimentary malnutrition.

It is worth saying that in the presence of these symptoms, one can doubt the diagnosis.

However, it should always be remembered that if a patient has a typical clinical picture of this disease and has these symptoms, then a diagnosis of ALS with features can be made.

Moderate cognitive impairment and dementia

Let's talk more about mild cognitive impairment and dementia in Lou Gehrig's disease. Here we often see gene mutations C9orf72. It leads to the development of ALS, frontotemporal dementia and their combination.

There are three options for the development of this disorder:

1. behavioral variant- this is when the patient's motivation decreases (apato-abulic syndrome). Or vice versa, there is disinhibition. A person's ability to actively and adequately communicate in society is reduced. Criticism is down. The flow of speech is impaired.
2. executory- Violation of action planning, generalization, fluidity of speech. The logical processes are broken.
3. Semantic (speech)- Fluid and meaningless speech is rarely manifested. However, dysnomia often occurs (they forget words), phonemic paraphasias (damage to the frontal speech zones). They often make grammatical errors and stutter. She has paragraphia (a writing disorder) and oral apraxia (cannot put her lips around the spirograph tube). There is also dyslexia and dysgraphia.

Diagnostic criteria for frontotemporal dysfunction according to D.Neary (1998)

Diagnostic criteria for frontotemporal dysfunction according to D.Neary include such mandatory features as:

• Insidious onset and gradual progression
• Early loss of self-control of behavior
• The rapid emergence of interaction difficulties in society
• Emotional flattening in the early stages
• Early decline in criticism

The diagnosis does not contradict the fact that such a disorder can occur before the age of 65. The diagnosis is called into question when the patient abuses alcohol. If such disorders are divorced acutely, they were preceded by a head injury, then the diagnosis of frontotemporal dysfunction is removed.

The patient is shown below. She has a symptom of empty eyes. Is not specific symptom. But with ALS, when a person cannot speak or move, this is something to look out for.

To the right is an example where the patient writes in telegraph style. She writes single words and makes mistakes.

See how thick the skin is in ALS. It is difficult for patients to pierce the skin with a needle electrode. In addition, there are difficulties in performing a lumbar puncture.

Revised El Escorial Criteria for ALS (1998)

Reliable ALS is set when signs of damage to the peripheral and central motor neurons are combined at three levels of the central nervous system out of four possible (trunk, cervical, thoracic and lumbar).

Likely- this is a combination of signs at two levels of the central nervous system. Some signs of damage to the central motor neurons are very high.

Probable laboratory susceptible- a combination of signs at the same level of the central nervous system in the presence of signs of damage to peripheral motor neurons in at least two limbs and the absence of signs of other diseases.

Possible ALS- a combination of features at the same level. Either there are signs of damage to the central motor neuron rostral to signs of damage to the peripheral motor neuron, but there are no ENMG data at other levels. Requires exclusion of other diseases.

Suspect- these are isolated signs of damage to the peripheral motor neuron in two or more parts of the central nervous system.

Progression of motor neuron disease

The progression of motor neuron disease can be divided into three types:

1. Rapid - loss of more than 10 points in 6 months
2. Average - loss of 5 - 10 points for six months
3. Slow - loss of less than 5 points in a month

Instrumental methods for diagnosing ALS

Instrumental diagnostic methods are designed to exclude diseases that are potentially curable or have a benign prognosis.

There are two methods of ALS diagnostics:

1. (EMG) - verification of the generalized nature of the process
2. Magnetic resonance imaging(MRI) of the brain and spinal cord - an exception focal lesions central nervous system, clinical manifestations of which are similar to those of the onset of MND

Amyotrophic Lateral Sclerosis - Treatment

Unfortunately, there is currently no complete treatment for amyotrophic lateral sclerosis. Therefore, this disease is still considered incurable. By at least, cases of recovery from ALS have not yet been recorded.

But medicine does not stand still!

Various studies are constantly being carried out. Clinics use methods that help the patient to ease the tolerance of the disease. We will discuss these clinical guidelines below.

There are also drugs that prolong the life of an ALS patient.

But it is worth saying that it is not necessary to carry out treatment with methods that have not yet been thoroughly investigated. There are some drugs that at first glance can improve the patient's condition. However, over time, everything comes full circle and the disease still begins to progress.

The same applies to stem cells. Studies have been conducted that have shown improvement at first. However, then, the person got worse and ALS disease began to progress again.

Therefore, on this moment stem cells is not the treatment to choose. In addition, the procedure itself is very expensive.

Pathogenetic therapy for Lou Gehrig's disease

There are drugs that slow the progression of Lou Gehrig's disease.

- presynaptic inhibitor of glutamate release. Extends the life of patients by an average of 3 months. You need to take while a person maintains self-service. Doses of 50 mg 2 times a day before meals every 12 hours.

In 3 - 12% of cases, the drug causes drug-induced hepatitis, increased pressure. Metabolized in men and smokers. They need a higher dose.

It is worth saying that the slowdown in progression cannot be felt. The drug does not make a person better. But the patient will be sick longer and later ceases to serve himself.

The drug is contraindicated in patients with certain and probable ALS with a disease duration of less than five years with a forced vital capacity of more than 60% and without tracheostomy.

The price of Riluzole in different pharmacies ranges from 9,000 to 13,000 rubles.

NP001 — active substance sodium chlorite. This medicine is an immune regulator for neurodegenerative diseases. Suppresses macrophage inflammation in vitro and in patients with amyotrophic lateral sclerosis.

3 months after droppers at a dose of 2 mg/kg, sodium chlorite stabilizes the course of the disease. It seems to stop progression.

What can not be applied

For ALS, do not use:

• Cytostatics (aggravate immunodeficiency in malnutrition)
• Hyperbaric oxygenation (aggravates already disturbed carbon dioxide washout)
• Infusions on physiological saline with hyponatremia in patients with ALS and dysphagia
• Steroid hormones (cause respiratory muscle myopathy)
• Branched-chain amino acids (shorten life)

Palliative therapy for Charcot's disease

The goal of palliative therapy for Charcot's disease is to reduce individual symptoms. As well as prolonging the life of the patient and maintaining the stability of its quality at a certain stage of the disease.

1. Treatment of fatal symptoms (dysphagia, nutritional and respiratory failure)

Treatment of Non-Fatal Symptoms of ALS

Now consider the treatment of ALS with non-fatal symptoms.

For starters, this reduction of fasciculations and cramps:

• Quinidine sulfate (25 mg twice daily)
• Carbamazepine (100 mg twice a day)

Can give drugs reducing muscle tone:

• Baclofen (up to 100 mg per day)
• Sirdalud (up to 8 mg per day)
• Centrally acting muscle relaxants (diazepam)

Fight against joint contractures:

• Orthopedic shoes (prevention of equinovarus foot deformity)
• Compresses (novocaine + dimexide + hydrocortisone / lidase / ortofen) for the treatment of humeroscapular periatrosis

Myotropic metabolic drugs:

• Carnitine (2 - 3 g per day) course 2 months, 2 - 3 times a year
• Creatine (3 - 9 g per day) course for two months pass 2 - 3 times a year

They also give multivitamin preparations. Neuromultivit, milgamma, lipoic acid preparations by intravenous drip. The course of treatment is 2 months and 2 times a year.

Fatigue treatment:

• Midantan (100 mg per day)
• Ethosuximide (37.5 mg per day)
• Physiotherapy

For the prevention of subluxation of the head humerus with flaccid paresis of the hands, unloading bandages are used to upper limbs Deso type. You need to wear 3-5 hours a day.

There are special orthoses. These are head holders, stop holders and hand splints.

There are also assistive devices in the form of crutches, walkers or belts for lifting a limb.

There are also special utensils and devices that facilitate hygiene and everyday life.

Treatment of dysarthria:

• Speech recommendations
• Ice applications
• Give drugs that reduce muscle tone
• Use tables with alphabet and dictionaries
• Electronic typewriters
• Multifunctional voice recorders
• Voice Amplifiers
• used computer system with sensors on the eyeballs to reproduce speech as text on the monitor (figure below)

Aspiration pneumonia in ALS

50-75% of patients with neurodegenerations and the elderly have swallowing problems, which occur in 67% of ALS patients. At 50% aspiration pneumonia deadly.

Diagnostic methods:

• Videofluoroscopy, APRS scales (aspiration-penetration scale) DOSS (dysphagia outcome severity scale)

Below we see the definition of the density and volume of liquid, nectar and pudding, which the patient should swallow.

Treatment of dysphagia

In the treatment of dysphagia (impaired swallowing), the following are used at the initial stage:

1. Food of a semi-solid consistency with a mixer, blender (mashed potatoes, jelly, cereals, yogurts, jelly)
2. Fluid Thickeners (Resourse)
3. Difficult to swallow dishes are excluded: with solid and liquid phases (soup with pieces of meat), solid and bulk foods (walnuts, chips), viscous foods (condensed milk)
4. Reduce products that increase salivation (fermented milk, sweet candy)
5. Exclude products that cause a cough reflex (spicy seasonings, strong alcohol)
6. Increase the calorie content of food (adding butter, mayonnaise)

Gastrostomy is used to treat progressive dysphagia. In particular, percutaneous endoscopic.

Percutaneous endoscopic gastrostomy (PEG) and enteral nutrition prolong life for ALS patients:

• ALS + PEG group — (38 ± 17 months)
• ALS group without PEG — (30 ± 13 months)

Treatment of respiratory failure

The treatment of respiratory failure is non-invasive intermittent ventilation (NIPPV, BIPAP, NIPPV), two-level positive pressure (inspiratory pressure higher than expiratory pressure).

Indications for ALS:

1. Spirography (FVC)< 80%)
2. Inspiratory manometry - less than 60 cm. Art.
3. Polysomnography (more than 10 episodes of apnea per hour)
4. Pulse oximetry (Pa CO2 ≥ 45 mmHg; decrease in nocturnal saturation ≥ 12% over 5 minutes)
5. arterial blood pH less than 7.35

Indications for breathing apparatus:

• Spinal ALS with forced vital capacity (FVC) 80-60% - isleep 22 (S)
• Bulbar BASS FVC 80-60% - isleep 25 (ST)
• Spinal ALS FVC 60-50% – isleep 25 (ST)
• FVC below 50% - tracheostomy (device VIVO 40, VIVO 50 - PCV, PSV modes)

Artificial (invasive) ventilation is safe, prevents aspiration and prolongs human life.

However, it contributes to the secretion, the risk of infection, complications from the trachea. As well as the risk of locked-in syndrome, addiction 24 hours a day and high cost.

Indications for invasive ventilation:

• Inability to adapt to NPVL or it lasts more than 16-18 hours a day
• At bulbar disorders With high risk aspiration
• When NVPL does not provide adequate oxygenation

Criteria limiting the transfer to mechanical ventilation in ALS:

1. Age
2. Disease progression rate
3. Possibility of communication
4. Frontotemporal dementia
5. Relationships in the family
6. Mental illness in a patient
7. Habitual intoxications
8. Fear of death

ALS patients who have been on mechanical ventilation for more than 5 years develop locked-in syndrome (18.2%), a state of minimal sociability (33.1%).

Psychotherapy for amyotrophic lateral sclerosis

Psychotherapy is also very important for amyotrophic lateral sclerosis. It is necessary for both the patient and his family members.

According to statistics, 85% of ALS patients suffer from mental disorders. And 52% suffer family members. At the same time, anxiety disorders predominate in relatives, and depressive disorders in patients.

Available alarm signals and by addiction. That is, the abuse of tobacco, drugs or alcohol. Patients account for 49%, and family members account for 80%. As a result, all this leads to the following consequences.

Pathogenesis of mental disorders in ALS

So, what happens to the human psyche at the stage diagnosis:

• Ambivalence (split) thinking
• Development of anxiety - drug and Internet addiction
• Intrusive thoughts - obsessional syndrome(repetition of examinations with different doctors)
• Violation of the mental state of relatives - comfort disorders (psychiatric cocoon)

At the stage development of neurological deficit:

• Denial of illness (inverted hysteria-like reaction)
• Or there is an acceptance of the disease (depression)

At the stage increasing neurological deficit:

• Deepening depression
• Refusal of treatment

Treatment of mental disorders

In general, in this case, with Charcot's disease, it is necessary to deal with treatment. mental disorders. This includes:

• Replacement of anticholinergics against salivation (atropine, amitriptyline) with butolotoxin and irradiation of the salivary glands
• Cholinomimetics (low doses of galantamine)
• Atypical antipsychotics - seroquel, possibly in drops - neuleptil
• Do not start treatment with antidepressants, as they increase anxiety. It is better to give something softer (azafen).
• Use of tranquilizers - alprazolam, strezam, mezapam
• Sleeping pills to use only when immobilized
• Pantogam

Occupational Therapy and Physical Therapy for ALS

Let's talk a little about occupational therapy and physical therapy for ALS. You will find out what it is and what it is for.

Physical Therapist helps the patient maintain optimal fitness and mobility, taking into account how this all affects life.

If physical therapy monitors how the patient's life changes, then another person is needed who will evaluate the very quality of the patient's life.

Ergotherapist is a specialist who helps the patient to live as independently and interestingly as possible. The specialist should delve into the peculiarities of the patient's life. Especially for patients with severe cases of the disease.

Stretch marks

Stretches and movements of maximum amplitude prevent contractures, reduce spasticity and pain. Including involuntary convulsive contractions.

You can do stretching with the help of another person or some external additional force. The patient can do this himself with the help of belts. But here you need to remember that with this method a person will waste energy.

Does muscle training help with ALS?

There are studies that say that the use of resistance exercises for the upper limbs in a patient with amyotrophic lateral sclerosis, led to an increase in static strength in 14 muscle groups (in 4 they did not increase).

And this is after 75 days of training. Therefore, any classes should be regular and long.

Progress in muscle strength shown in the study

As you can see, there was a significant increase in most groups muscle strength. As a result of this activity, it became easier for a person to get items from the top shelf. Or pick up an item and put it on a shelf.

In the therapy itself, movements were made along a trajectory close to those used in PNF. This is the moment when the doctor gives resistance to the movement of the patient. Of course, such resistance should not be very strong. The main thing is to catch the right degree.

As a rule, many movements are made diagonally. For example, take your leg diagonally. The exercises themselves were done with the help of elastic bands (drums). Although they were partially made with the help of resistance with their hands.

Methodology for conducting classes

Here is the training methodology:

• The action was performed with overcoming resistance throughout the movement
• The movement in one direction took 5 seconds
• The session consisted of two sets of 10 movements.
• Rest between sets was about 5 minutes.
• Classes were held 6 times a week:
  • 2 times with a specialist (overcoming the resistance of the hands of a specialist)
  • 2 times with a family member (same arm resistance)
  • 2 times alone with elastic bandages
• The results from the table appeared after 75 days (65 lessons) of the course

What is the effect of force

Why does strength increase even when a motor neuron is damaged? A sedentary lifestyle can lead to cardiovascular detraining.

In other words, those muscles that are not affected also begin to weaken. And it is on their training that the effect of increasing strength is based.

Another detraining occurs because it falls functional support. With a sedentary lifestyle, there is little oxygen. Therefore, exercise with moderate physical activity improves the overall functioning of the body.

Intensity of training in Lou Gehrig's disease

I want to say that exercises with strong resistance do not give any effect. Not only do they not give, they can also harm a patient with Lou Gehrig's disease.

But exercises of moderate intensity lead to an improvement in the work of muscles that are not affected by significant weakness. If the muscle practically does not move, then you should not count on an increase in its strength.

However, there are muscles that make movements, but weakly.

Even people with respiratory failure using non-invasive assisted ventilation may experience improvements in muscle function as a result of moderate exercise.

Regular exercise with moderate resistance helps improve static strength in some muscles.

To determine the significant and insignificant load, the Borg scale is used.

Borg scale

From 0 to 10, we can determine the subjective sensations that a person has when he does exercises.

No matter how much effort the patients make. No matter what exercises and duration of the walk they were offered. Most importantly, their effort should feel like nothing more than "medium" or "almost heavy." That is, the load should not go above level 4.

There is such a calculation that helps determine the reserve of the heart. That is, at what heart rate you can easily and safely train.

• Load intensity= Resting heart rate + 50% to 70% heart reserve
• Heart reserve= 220 - age - resting heart rate

Aerobic training program for ALS

There is also a 16 week aerobic training program for ALS. It is done three times a week. A couple of times we do at home on a bicycle ergometer and on the steppe. Then once in the hospital under the supervision of a physical therapist.

• 1-4 weeks 15 to 30 minutes
• From 5 weeks to half an hour

Step exercises(a step that is climbed and then descended):

• First 5 weeks (3 minutes)
• 6-10 weeks (4 minutes)
• 11-16 weeks (5 minutes)

Classes in the hospital:

1. 5 minutes warm-up (pedaling without load)
2. 30 minutes of moderate exercise (15 minutes cycling, 10 minutes track, 5 minutes step)
3. 20 minutes of strength training (anterior thigh, biceps and triceps)
4. 5 minutes of the final part

And this program also led to the fact that the patients then improved their physical condition.

Principles for restoring daily activities

The exercise therapist and occupational therapist should always think of three things in order to improve a person's daily activities:

1. The specialist must evaluate and optimize the physical capabilities of the patient
2. Given these possibilities, you need to select the optimal posture for each action.
3. Adapt the patient's environment and see how physical abilities can be improved

Walking support for Charcot's disease

Very often, specialists need to solve the problem of supporting the walking of their patient with Charcot's disease. There are several solutions here. You can use elbow crutches because they are easier to lean on.

But sometimes it is enough to use ordinary canes. But they require strength because you need to hold the whole hand. And to walk on slippery surfaces, I recommend buying special "cats" at the pharmacy.

If the foot sags, then a stop holder is needed.

If a person is too tired or simply cannot walk, then a wheelchair will be needed. And what is the optimal model to choose - this issue should be jointly decided by the ergotherapist and the physical therapist.

In a wheelchair, a person should be comfortable, comfortable. In addition, the device itself should not require a lot of energy from the patient.

It is also necessary to take into account the modularity (options) of the stroller. They help carry out daily activities.

For example, a wheelchair may use an anti-tilt device to prevent it from falling. Transit wheels can also be used. So you can drive where a wide stroller does not fit.

Sometimes we have to provide brakes for the maintainer. Headrests, side belts and so on can also be included.

As you can see, the adaptation and selection of a stroller is also very important. main part for an ALS patient.

seat height

Seat height is also important. From a higher surface, it will be much easier for the patient to get up. Also at a high level, a person will sit more evenly. Indeed, in this case, the back muscles are activated.

Therefore, it is not necessary to seat the patient in a low chair. He will be uncomfortable in it. In addition, it will be much more difficult to remove a patient from such a chair.

So besides the stroller, you have to adjust optimal level beds and chairs.

meal

Eating depends on which table the patient is sitting at. Avoid round tables as they make sitting difficult.

If a person has a bad head and food falls out of his mouth, then in no case make a high headboard. This will make it very difficult for him to swallow.

If you put the patient on a high headboard, then at least make sure that his entire back lies on this headboard. That is, the back should not bend.

If a person lies completely horizontal, then he will have a very low respiratory capacity. If it is raised by 30º, it will be much better.

In the position on the side and on a high headboard it will be better than just on the side. But the worst position is on the back and horizontally.

If sitting, then breathing will be even better! Remember that we always eat sitting down. Therefore, tilting the head forward always helps the pharynx.

There are also many adapted cutlery that are easier to hold by hand. For example, devices with thickened handles. There are even special clamps on the brush and much more.

But be careful if the person has dysphagia! In this case, you need to decide whether to maintain active amateur performance or a safe sip. The latter will always take precedence.

If a person has dysphagia, then it will be difficult for him to think about a fictitious pharynx and, in addition, weak hand bring this food to you. Therefore, in this case, you do not need to chase adaptation to self-service.

Drink

There are cutlery that help to carry out drinking. For example, there are special glasses with a cut. As a result, you can drink from such a glass without throwing your head back. The nose drops into this notch, making drinking safer.

There is also a mug with two handles. It is very comfortable to carry with two hands.

However, a special nipple on the top cover can also be dangerous for dysphagia. If you drink from such a glass, then a person will have to throw back his head.

ALS positioning program

In order to coordinate the regime of work and rest, as well as to balance the ability of the ALS patient from excessive fatigue, it is necessary to adhere to a special program (schedule).

Here is a sample positioning program for a severely disabled person who may be upright for a while.

ALS disease - photo

Below is a photo related to ALS disease. All images are clickable to enlarge.

Amyotrophic Lateral Sclerosis (ALS; Amyotrophic Lateral Sclerosis) is a neurodegenerative disease characterized by the death of central and / or peripheral motor neurons, steady progression and death (based on the fact that the disease is based on selective damage to motor neurons, ALS is also called “motor neuron disease "; in the literature, ALS is also referred to as Charcot's disease, Lou Gehrig's disease). The death of the above motor neurons is manifested by skeletal muscle atrophy, fasciculations, spasticity, hyperreflexia, and pathological pyramidal signs in the absence of oculomotor and pelvic disorders.

It usually takes about 14 months from the onset of the first symptoms of the disease to the final diagnosis in patients with ALS. The most common reasons for a long period of diagnosis are unusual clinical manifestations of the disease, the doctor's lack of thought about the possibility of developing ALS in a particular case, and misinterpretation of the results of neurophysiological and neuroimaging examinations. Unfortunately, the delay in diagnosing the disease leads to the appointment of inadequate therapy for such patients and the emergence of psychosocial problems in the future.

ALS is observed throughout the world everywhere. Analysis of the results of population studies shows that the incidence of ALS in European countries is 2-16 patients per 100,000 people per year. 90% are sporadic cases. Only 5 - 10% fall on hereditary (family) forms. Attempts to identify a clear genetic pattern characteristic of sporadic ALS variants have so far been unsuccessful. With regard to familial forms of ALS, 13 genes and loci have been identified that have a significant association with ALS. The typical clinical ALS phenotype results from mutations in the following genes: SOD1 (responsible for Cu/Zn ion-binding superoxide dismutase), TARDBP (also known as TDP-43; TAR DNA-binding protein), FUS, ANG (encodes for angiogenin, ribonuclease), and OPTN (codes for optineurin). The SOD1 mutation is associated with the rapid progression of the disease (ALS), the pathophysiological pattern of which is not fully known.

read also the article molecular structure amyotrophic lateral sclerosis in the Russian population” N.Yu. Abramycheva, E.V. Lysogorskaya, Yu.S. Shpilyukova, A.S. Vetchinova, M.N. Zakharova, S.N. Illarioshkin; FGBNU "Scientific Center of Neurology"; Russia, Moscow (journal "Neuromuscular Diseases" No. 4, 2016) [read]

It is assumed that the main pathogenetic factor in mutations in the SOD1 gene is the cytotoxic effect of the defective enzyme, and not a decrease in its antioxidant activity. Mutant SOD1 can accumulate between the layers of the mitochondrial membrane, disrupt axonal transport, and interact with other proteins, causing their aggregation and disrupting degradation. Sporadic cases of the disease are probably associated with exposure to unknown triggers, which (like mutant SOD1) realize their effects under conditions of increased functional load on motor neurons, which leads to their selective vulnerability associated with increased energy costs, high demand for intracellular calcium, and low expression of calcium-binding proteins, AMPA-type glutamate receptors, some antioxidants, and anti-apoptotic factors. Strengthening the functions of motor neurons causes an increased release of glutamate, glutamate excitotoxicity, accumulation of excess intracellular calcium, activation of intracellular proteolytic enzymes, release of excess free radicals from mitochondria, damage to microglia and astroglia, as well as the motor neurons themselves, with subsequent degeneration.

ALS is more common in men. At the same time, the incidence of the disease in familial forms of ALS does not have a significant difference between men and women. Most often, ALS debuts at the age of 47-52 years with its family variants and at 58-63 years with sporadic forms of the disease. According to foreign authors, significant risk factors for the development of ALS are male gender, age over 50 years, smoking, mechanical injury received within 5 years before the onset of the disease, sports and intensive physical work. The disease is practically not observed after 80 years. The average life expectancy of patients with ALS is 32 months (however, the life expectancy of some patients with ALS can reach 5-10 years after the onset of the disease).

The following clinical forms of the disease are distinguished: [ 1 ] the classic spinal form of ALS with signs of damage to the central (CMN) and peripheral motor neuron (PMN) on the arms or legs (cervicothoracic or lumbosacral localization); [ 2 ] bulbar form of ALS, manifesting speech and swallowing disorders, followed by movement disorders in the limbs; [ 3 ] primary lateral sclerosis, manifested by signs of damage exclusively to the CMN, and [ 4 ] progressive muscular atrophy, when only PMN symptoms are observed.

Main clinical criteria The diagnosis of ALS is based on the presence of signs of damage to the CMN and PNM at the bulbar and spinal levels. The debut of the disease is possible with the development of stem disorders (about 25%), impaired function of movement in the limbs (about 70%), or with a primary lesion of the trunk muscles (including respiratory ones) - 5%, followed by the spread of the pathological process to other levels.

The defeat of the CMN is manifested by spasticity and weakness in the limbs, the revival of deep reflexes and the appearance of pathological signs. The pathological process involving PNM manifests with fasciculations, muscle atrophy, and weakness. Signs of pseudobulbar paralysis observed in ALS include spastic dysarthria, characterized by slow, difficult speech, often with a hint of nasality, increased chin and pharyngeal reflexes, and symptoms of oral automatism. Bulbar paralysis is manifested by atrophy and fasciculations in the tongue, dysphagia. Dysarthria in this case is accompanied by severe nasolalia, dysphonia and a weakening of the cough reflex.

A typical clinical sign of ALS is fasciculations - visible involuntary contractions of individual muscle groups. They arise as a result of spontaneous bioelectrical activity of intact motor units (i.e. motor neurons). The detection of tongue fasciculations is a highly specific sign of ALS. Muscle atrophy and decline motor activity are also the most common symptoms of ALS. At a certain stage of the disease, the severity of these disorders requires outside help in everyday life. Dysphagia develops in most patients with ALS and is accompanied by weight loss, which is associated with a poor prognosis of the disease. Respiratory disorders form in most patients with ALS, leading to shortness of breath when physical activity, orthopedic, hypoventilation, hypercapnia, morning headaches. The appearance of shortness of breath at rest is a sign of an imminent lethal outcome.

An atypical pattern of initial signs of ALS includes weight loss (prognostically unfavorable sign), the presence of cramps, fasciculations in the absence muscle weakness, emotional disorders, as well as cognitive disorders of the frontal type.

In most patients, sensory nerves and the autonomic nervous system, which controls the functions of internal organs (including pelvic organs), as a rule, are not damaged, however, isolated cases of violations still occur. The disease also does not affect a person's ability to see, smell, taste, hear, or feel touch. The ability to control the eye muscles almost always remains, except exceptional cases, which is very rare.

Elderly age, early development respiratory disorders and the onset of the disease with bulbar disorders are significantly associated with low patient survival, while the classic spinal form of ALS, young age, and a long period of diagnostic search in this pathology are independent predictors of higher patient survival. And clinical form ALS with "loose joints" and progressive muscular atrophy are characterized by a slower increase in symptoms than other clinical variants of the disease. In the bulbar form of ALS, which is most often observed in women over 65 years of age, in cases where the oropharyngeal muscles are affected with a clinical picture of predominantly pseudobulbar palsy, the prognosis of life is 2–4 years. In addition, disease progression in patients with primary lateral sclerosis occurs more slowly than in patients with the classical form of ALS.

The existence of some diseases that have a similar clinical pattern to ALS requires careful diagnosis of all patients with suspected ALS. The standard in diagnostics are neuro-physiological, neuro-imaging examination, as well as a number of laboratory tests. In cases of isolated lesions of the PMN, it is necessary to perform genetic research for Kennedy's disease, X-linked bulbospinal atrophy and spinal muscle atrophy. In addition, muscle biopsy may be performed to exclude certain myopathies, such as polyglucosane body disease. At the same time, muscle biopsy detection of fibers mixed type atrophy is a pathognomonic sign of ALS.

about the ALS clinic and the differential diagnosis of ALS, see also the article: Clinic and differential diagnosis amyotrophic lateral sclerosis (per site)

Currently, the sole purpose of performing neuroimaging studies (usually MRI) in patients with ALS is exclusion (differential diagnosis of an alternative pathological process). MRI of the brain and spinal cord in patients with ALS reveals signs of degeneration of the pyramidal tracts in about half of the cases, which is more typical for the classical and pyramidal variants of ALS. Other signs include atrophy of the motor cortex. In patients with clinically significant ALS and the presence of bulbar and/or pseudobulbar syndromes, the role of neuroimaging is not significant.

The standard neurophysiological examination of patients with suspected ALS includes a study of the speed of impulse conduction along nerve fibers, electromyography (EMG), and sometimes transcranial magnetic stimulation (which may reveal a decrease in central motor conduction time along the corticolumbar and/or corticocervical pyramidal tracts, as well as a decrease in motor cortex excitability). Examination of the peripheral nerves is essential to rule out some ALS-like disorders, especially demyelinating motor neuropathies.

The "gold standard" for diagnosing PMN lesions is needle electromyography (EMG), which is performed at three levels (head or neck, arm, leg). Signs of damage to the PMN in this case are: spontaneous activity in the form of potentials of fasciculations, fibrillations and positive sharp waves, as well as a tendency to increase the duration, amplitude and number of phases of motor unit potentials (signs of neuronal denervation).

The only laboratory method to confirm the diagnosis of ALS is molecular genetic analysis of the SOD1 gene. The presence of a mutation of this gene in a patient with suspected ALS makes it possible to attribute it to a highly reliable diagnostic category of "clinically reliable laboratory-confirmed ALS".

skeletal muscle biopsy, peripheral nerve and other tissues is not necessary in the diagnosis of motor neuron disease, [ !!! ] except in those cases where there are clinical, neurophysiological and neuroradiological data that are not characteristic of the disease.

note! Respiratory status should be assessed in ALS patients every 3 to 6 months from the time of diagnosis (Lechtzin N. et al., 2002). According to US and European guidelines, all patients with ALS should have regular spirometry. Other recommendations include nocturnal pulse oximetry, arterial blood gases, polysomnography, maximum inspiratory pressure (MIP) and expiratory pressure (MEP) and their ratio, transdiaphragmatic pressure, nasal pressure (SNP) (if orbicularis oculi is weak). The inclusion of research data in the assessment of respiratory disorders in combination with the determination of forced vital capacity (FVC) can help in the early detection of changes in respiratory function and the implementation of non-invasive lung ventilation (NIVL) in the initial stages of respiratory failure (for more details, see article # 12 - see below) .

The problem of ALS treatment is that 80% of motor neurons die before the clinical manifestations of the disease. To date, the world does not have effective method ALS treatment. Riluzole (also sold under the name Rilutek) is the gold standard treatment for ALS. This drug (which is not registered in Russia) has a pathogenic effect, since it reduces glutamate excitotoxicity. But due to the fact that it slows down the progression of the disease by only 2-3 months, in fact, its effect can be attributed to palliative. The drug is recommended to be taken while the ALS patient is participating in self-care, 50 mg 2 times a day before meals, while the safety of speech and swallowing in tetraparesis is also considered participation in self-care. The drug is canceled or not prescribed: with severe tetraparesis and bulbar disorders, patients with ALS who were diagnosed more than 5 years after the onset of ALS, with extremely rapid progression, with tracheostomy and mechanical ventilation, with hepatic and kidney failure. Another gold standard of palliative therapy for ALS is non-invasive ventilation (NVL). NIV reduces respiratory muscle fatigue and tension in the respiratory neurons, which are the most resistant to ALS. This leads to a prolongation of the life of ALS patients for a year or more, provided that the patient regularly consults with a doctor, does spirography, increases inspiratory and expiratory pressures with a difference of 6 cm aq. pillar in the device. Note: pathogenetic treatment No ALS - riluzole and NIV can prolong the patient's life for several months.

Read more about ALS in the following sources:

1 . head "Amyotrophic lateral sclerosis" V.I. Skvortsova, G.N. Levitsky. M.N. Zakharov; Neurology. National leadership; GEOTAR-Medicine, 2009 [read];

2 . article "Amyotrophic lateral sclerosis ( modern ideas, prediction of outcomes, evolution of medical strategy)" Zhivolupov S.A., Rashidov N.A., Samartsev I.N., Galitsky S.A., Military Medical Academy. CM. Kirov, St. Petersburg (magazine "Bulletin of the Russian military medical academy"No. 3, 2011) [read];

3 . article "Amyotrophic lateral sclerosis: clinic, modern methods of diagnosis and pharmacotherapy (literature review)" Sklyarova E. A., Shevchenko P. P., Karpov S. M., Stavropol State Medical University, Department of Neurology, Neurosurgery and Medical Genetics, Stavropol [read];

4 . lecture "On the pathogenesis and diagnosis of motor neuron disease (lecture)" V.Ya. Latysheva, Yu.V. Tabankova, Gomel State Medical University (magazine "Problems of Health and Ecology" No. 1, 2014);

5 . article "Recommendations for the provision of palliative care for amyotrophic lateral sclerosis" M.N. Zakharova, I.A. Avdyunina, E.V. Lysogorskaya, A.A. Vorobiev, M.V. Ivanova, A.V. Chervyakov, A.V. Vasiliev, Federal State Budgetary Scientific Institution "Scientific Center of Neurology"; Russia, Moscow (journal "Neuromuscular Diseases" No. 4, 2014) [read];

6 . article "Amyotrophic lateral sclerosis: clinical heterogeneity and approaches to classification" I.S. Bakulin, I.V. Zakroishchikova, N.A. Suponeva, M.N. Zakharov; FGBNU "Scientific Center of Neurology"; Moscow (journal "Neuromuscular diseases" No. 3, 2017 ) [read ];

7 . article "Clinical polymorphism of amyotrophic lateral sclerosis" E.A. Kovrazhkina, O.D. Razinskaya, L.V. Gubsky; Federal State Budgetary Educational Institution of Higher Education “Russian National Research Medical University named after N.N. N.I. Pirogov", Moscow (Journal of Neurology and Psychiatry, No. 8, 2017) [read];

8 . article " Deontological aspects amyotrophic lateral sclerosis” T.M. Alekseeva, V.S. Demeshonok, S.N. Zhulev; FSBI "National Medical Research Center named after N.N. V.A. Almazov, Ministry of Health of the Russian Federation, St. Petersburg; Federal State Budgetary Educational Institution of Higher Education “North-Western State Medical University named after I.I. I.I. Mechnikov” of the Ministry of Health of the Russian Federation, St. Petersburg (journal “Neuromuscular Diseases” No. 4, 2017) [read];

9 . article "Preclinical medical genetic counseling in amyotrophic lateral sclerosis" Yu.A. Shpilyukova, A.A. Roslyakova, M.N. Zakharova, S.N. Illarioshkin; FGBNU "Scientific Center of Neurology", Moscow (journal "Neuromuscular Diseases" No. 4, 2017) [read];

10 . article " Clinical case late debut spinal amyotrophy in an adult patient - a stage in the development of amyotrophic lateral sclerosis? T.B. Burnasheva; Israeli Medicine Center, Almaty, Kazakhstan (Medicine magazine No. 12, 2014) [read];

11 . article “Amyotrophic lateral sclerosis with enlargement of the central canal of the spinal cord according to magnetic resonance imaging” Mendelevich E.G., Mukhamedzhanova G.R., Bogdanov E.I.; Federal State Budgetary Educational Institution of Higher Education "Kazan State Medical University" of the Ministry of Health of the Russian Federation, Kazan (journal "Neurology, Neuropsychiatry, Psychosomatics" No. 3, 2016) [read];

12 . article "Methods for diagnosing and correcting respiratory disorders in amyotrophic lateral sclerosis" A.V. Vasiliev, D.D. Eliseeva, M.V. Ivanova, I.A. Kochergin, I.V. Zakroishchikova, L.V. Brylev, V.A. Shtabnitsky, M.N. Zakharov; FGBNU "Scientific Center of Neurology", Moscow; GBUZ "City Clinical Hospital. V.M. Buyanov, Moscow; Federal State Budgetary Educational Institution of Higher Education “Russian National Research Medical University named after N.N. N.I. Pirogov", Moscow (magazine "Annals of Clinical and Experimental Neurology" No. 4, 2018) [read];

13 . article "Amyotrophic lateral sclerosis: mechanisms of pathogenesis and new approaches to pharmacotherapy (literature review)" T.M. Alekseeva, T.R. Stuchevskaya, V.S. Demeshonok; FSBI "National Medical Research Center named after N.N. V.A. Almazov, Ministry of Health of the Russian Federation, St. Petersburg; St. Petersburg GBUZ "City general hospital No. 2, St. Petersburg; Federal State Budgetary Educational Institution of Higher Education “North-Western State Medical University named after I.I. I.I. Mechnikov” of the Ministry of Health of the Russian Federation, St. Petersburg (journal “Neuromuscular Diseases” No. 4, 2018 ) [read ]

Fund for helping patients with amyotrophic lateral sclerosis(information for patients and relatives)

© Laesus De Liro

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