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Neuromuscular disorders

One often speaks in a simplistic manner of muscle disease, but what is meant is neuromuscular diseases. What is the difference? Strictly speaking, muscle diseases are only diseases of the muscle itself. These include the muscular dystrophies, the muscle inflammation (myositis), and the metabolic diseases of the muscle, the metabolic myopathies.

The neuromuscular diseases also include the diseases of the muscle-activating (innervating) nerve fibers. The neural and spinal muscular atrophies are particularly worth mentioning here. The muscle is the organ whose weakness makes the disease stands out. However, it is only indirectly affected by the disease of the nerve. To simplify matters, we also speak of muscle diseases here.

Overview of the various muscle diseases (neuromuscular diseases)

Schematic overview

The diagram shows the structures involved in motor skills:

- brain

- Spinal cord

- Nerve fibers

- Muscles

Representing many nerve cells and fibers, we represent one in the area called the motor cortex of the brain and one in the area of ​​the spinal cord.

The extension of the nerve cell in the brain (first motor neuron or central motor neuron) pulls into the brain stem or spinal cord and is linked there to a second nerve cell.

From this nerve cell (second motor neuron or peripheral motor neuron or alpha-motor neuron) in turn, an extension (nerve fiber = axon) pulls up to a muscle.

These are the nerve fibers that run as a bundle on the arms and legs, e.g., median nerve. We call the connection point of the nerve fiber to the muscle a motor endplate. It is a nerve fiber supplies (innervates) several muscle fibers of a muscle.

What is the cause of neuromuscular diseases?

These diseases have very diverse causes. For some of them, the cause is genetic, that is to say that the abnormality of a gene appears spontaneously or is transmitted by the parents. This genetic abnormality or "mutation." will cause a malfunction of the cell which is, depending on the case, the motor neuron, the peripheral nerve or the muscle and be responsible for the disease. In other cases, it is poor functioning of immunity which will cause damage to the nerves (dysimmunity neuropathies), the neuromuscular junction (myasthenia gravis) or inflammation of the muscles (myositis). There are many other possible causes: drug or environmental toxicity, vitamin deficiency, endocrine or general diseases, infections.

How does neuromuscular disease manifest?

It is most often a loss of strength by lack of muscle control or by the destruction of the atrophied muscle. This can cause difficulty in walking or using your arms or hands. It can also be muscle pain that appears during exercise. Pain in the feet or hands or muscle cramps predominantly at night may be due to a disease of the peripheral nerves, as well as disturbances in balance or abnormal sensations such as tingling. If other muscles in the body are affected, the disease can manifest itself as double vision, drooping eyelids, difficulty speaking, swallowing, and breathing. These manifestations can be transient or permanent, depending on the disease.

Symptoms

Typical symptoms of most muscle diseases are

- Muscle weakness and rapid fatigue.

- Muscular atrophy (= muscle weakening).

- With some illnesses also muscle pain and muscle cramps.

- If the nerve fibers are also affected 

- Emotional disturbances can occur, especially on the feet.

Muscular dystrophy

Weaknesses are at the forefront of muscular dystrophies, often affecting the muscles close to the trunk. In the case of the limb shape, we speak of the pelvic or shoulder girdle type, depending on whether the hip and pelvic muscles are primarily affected.

In the case of Becker and Duchenne type muscular dystrophy, the hip muscles are particularly affected initially. Depending on the type and course of the disease, however, the weaknesses can spread to other muscle groups or, as with facioscapulohumeral muscular dystrophy, affect the facial muscles. Which muscle groups are affected and what the course depends on the specific disease.

The affected muscles also become weaker (atrophy). However, certain muscle groups can appear very strong and well-developed on the outside, although the muscles are partly replaced by connective and fat tissue. This is particularly typical of the calves. This is also referred to as pseudohypertrophy. "Hypertrophy" means that the tissue has grown and become more pronounced. The prefix "pseudo" indicates that in this case, the strong expression of the muscle only seems so. The functional muscle tissue is reduced. Contrary to popular belief, pseudohypertrophy of the calves can occur not only in muscular dystrophies but also in other neuromuscular disorders, such as spinal muscular atrophies.

Pain in the musculoskeletal system is often the result of incorrect and excessive strain. The weakened muscles have to work harder to achieve the tasks set, for example, keeping the body upright. This can lead to muscle tension. In addition, the weakness of the muscles affects the ligaments and joints unfavorably. That, too, can cause pain. The pain, in turn, leads to increased tension, which in turn leads to increased incorrect posture. 

In some muscular dystrophies, there is also an involvement of the heart muscles. Cardiac arrhythmias have to be treated; reduced resilience of the heart has to be considered, especially during therapy.

Myotonia

The myotonic diseases are characterized by a stiffness of the muscles. Movements can sometimes only be slow. This is the focus of the Myotonia congenita Thomsen and Becker.

 If it is present to a relevant extent, it primarily affects the hand muscles. Weaknesses occur mainly in the muscles away from the trunk. Other organ systems, such as the heart, eyes, and body glands, can also be affected by this disease. With myotonic dystrophy type 2 (PROMM), on the other hand, the weaknesses are not very pronounced. However, several organ systems are also affected here. We observe muscle pain here more often than with other neuromuscular diseases.

Metabolic myopathies

They are characterized by a disruption in the supply or production of energy. This is how muscle fibers absorb and store carbohydrates and fats. However, you cannot break them down and feed them into the energy cycle. Depending on the type of illness, there are weaknesses in the muscles close to the trunk, reduced endurance performance, or stress-related muscle pain. Here too, the extent of the symptoms varies widely, from only minor impairments to death in childhood.

Of particular note are the M. Pompe (linked to M. Pompe), the McArdle disease (linked to McArdle disease), and the mitochondrial myopathies (linked to mitochondrial myopathies).

Inflammation of the muscles (myositides)

Muscle inflammation is a non-uniform group of muscle diseases. It is a disorder of the body's defenses, a so-called autoimmune disease. The body's defense recognizes the body's own structures, e.g., B. parts of the muscle as foreign and fights them. This leads to weaknesses in polymyositis, especially the muscles close to the trunk, i.e., the shoulder and pelvic girdle area. The symptoms are progressive over weeks and months. Muscle pain is also occasionally reported. If inflammatory skin changes occur, dermatomyositis can be assumed. On the other hand, if there are other symptoms such as joint pain or circulatory disorders, another inflammatory connective tissue disease such as scleroderma, lupus erythematosus, and others must be looked for.

As an autoimmune disease, these muscle inflammations can usually be treated well.

Inclusion body myositis also belongs to the group of muscle inflammations, although the inflammatory process probably does not play the primary role in the course of the disease.

Neuromuscular junction disorders - myasthenia gravis and Lambert-Eaton syndrome

Both myasthenia gravis and Lambert-Eaton syndrome (often also as Lambert-Eaton myasthenic syndrome, LEMS) are classic autoimmune diseases. The body attacks parts of the body itself, in both disease structures of the transition from nerve to muscle, the so-called motor endplate.

While in myasthenia gravis, the antibodies affect the structures of the motor endplate on the membrane of the muscle (post-synaptic disorder). In the Lambert-Eaton syndrome, calcium channels in the membrane of the nerve fiber (pre-synaptic disorder) are the targets of the antibodies.

In the case of myasthenia gravis, the strength of the muscles typically decreases rapidly when under stress, but after sufficient rest, the muscles can then be used again depending on the severity of the disease. The muscles that move the eyes and lift the eyelids are typically affected. The weakness can also extend to the muscles close to the trunk, especially the shoulder and neck area. The respiratory muscles can also be affected in severe cases. The disease can usually be influenced well by medication.

Symptoms of Lambert-Eaton syndrome are weaknesses and premature fatigue of the muscles close to the trunk, especially the pelvic and thigh muscles. There are weaknesses in the eye, speech, and swallowing muscles. During the test, the force is typically very low at first, then increases a few seconds before there is premature exhaustion. Vegetative disorders such as dry mouth, reduced sweating, bladder emptying disorders, and constipation also occur. Around half of the patients develop the disease as a result of a tumor, i.e., a so-called paraneoplastic syndrome. Lambert-Eaton syndrome is usually also available for drug treatment.

Spinal muscular atrophy

The disorders in spinal muscular atrophies look very similar to those in muscular dystrophies. The cause here is a disease of the nerve cells in the spinal cord, the branches of which extend, the nerve fibers, to the muscles on the trunk, arms, and legs. When these cells die, the muscles are no longer innervated (activated). This weakens the muscles and reduces their mass; that is, they atrophy. Here, too, the muscle groups close to the trunk are often affected.

There are forms that are already present at birth and progress rapidly, such as the Werdnig-Hoffmann type. Other forms of progression only appear in adolescence or adulthood with slow progressions, such as the Kugelberg-Welander type.

A special facet is the bulbospinal muscle atrophy (Kennedy type), which occurs in men and can also affect the swallowing muscles.

Poliomyelitis and postpoliomyelitis syndrome

Poliomyelitis is a disease of the nerve cell of the second motor neuron in the spinal cord. A virus damages the cell and can go under. Today the disease is still active in parts of Asia and Africa; in Europe, it is considered extinct.

As there is a risk of viruses being introduced from Asia and Africa, the Robert Koch Institute's Standing Vaccination Committee (STIKO) recommends that children and adolescents be vaccinated regularly and for adults according to certain criteria.

The musculoskeletal system is strained due to the paralysis that persists after the onset of the disease (so-called polio residual condition). This can cause joint wear (arthrosis) and disorders of the spine with pain.

To be differentiated from this is the so-called post-poliomyelitis syndrome (or shorter: post-polio syndrome or PPS). Decades after polio, muscle weakness occurs and slowly progresses. This particularly affects muscle groups that were primarily significantly weakened but have recovered well. Here the patients often first report a decrease in endurance performance and resilience, and in the course, also increasing paralysis. The literature describes a decrease in muscle strength of around 1% per year. Patients also report general fatigue, sleep disorders, and other disorders.

Neural Muscular Atrophy (HMSN)

In the case of neural muscle atrophies (HMSN), the muscles that are far from the trunk are affected, i.e., those of the lower legs and feet as well as the hands. It is a disease of the nerve fibers; the longest nerve fibers have the greatest risk of becoming ill. Therefore, the symptoms are most likely to be distant from the trunk.

Foot elevation is often particularly affected. Feeling disorders can also occur on the feet but are usually at most slight. The symptoms can vary greatly, even within a family; the extent of the symptoms varies widely.

Diagnosis

As with all other diseases, the diagnosis of muscle diseases comes before therapy. In the anamnesis (questioning the patient about the patient's previous history), the beginning of the functional disorders, the course, and the occurrence of similar disorders in other family members are of interest.

General and special examinations

The general physical examination looks for general abnormalities, such as changes in the joints, enlarged organs, lung function, etc. In the special neurological examination, the function of the nerves and muscles and their control is checked. In the case of paralysis, the focus, expression, and type of muscular weaknesses are determined more precisely. These initial measures alone can often already be used to assign muscle disease.

Electroneurography and electromyography

A more precise differentiation can be made by the neurophysiological examination methods, in particular by electroneurography and electromyography. With electroneurography, we determine the nerve conduction speed and the functionality of the nerve fibers. Nerves are electrically stimulated. We measure muscle flows using electromyography. It can be determined whether the supplying and activating nerves are impaired or whether the muscles themselves are diseased. As a rule, these examinations already clarify whether there is a disease of the nerves or the muscles. This allows it to be narrowed down diagnostically more precisely.

Laboratory tests

These also provide important information: The "CK" (= creatine kinase), a muscle enzyme, is often found to an increased extent in the blood in muscle disease. Other enzymes and metabolic products of the muscles, certain antibodies (proteins of the body's defense) as well as studies of routine and other laboratory parameters in blood and urine supplement the spectrum depending on the question.

Imaging diagnostics

MRI (magnetic resonance or nuclear spin tomography) and ultrasound can be particularly useful. This enables us to assess the structures of the muscles and their changes without any significant strain on the patient. In both studies, muscles or other parts of the body are displayed in layers. Unfortunately, these examinations have little meaning for most muscle diseases.

Further investigations

The muscle biopsy allows the muscle to be examined under the light and electron microscope. This enables us to examine the metabolic processes in the muscle precisely (biochemistry).

Other examinations serve to demonstrate the involvement of other organ systems such as the examination of the heart currents (EKG), ultrasound of the heart, and abdominal organs.

Molecular genetic diagnostics

You are of great importance today. Parts of the chromosomes, the genome, are examined. By means of direct genetic detection of the changed chromosome sections (genes), we can precisely determine the disease and its cause.

The number of different muscle diseases is very high, but the molecular diagnostic examination is very complex. Therefore, the diagnosis must be narrowed down as clearly as possible before the molecular genetic examination. In a few cases, however, the molecular genetic examination can also be carried out primarily, for exampleNeuromuscular disorders, if muscular dystrophy of the Duchenne type is suspected if the previous history and the neurological findings are already indicative.


Author: Vicki Lezama


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