Motor neuropathy

Motor neuropathy or motor neuropathy, which is distinguished among neurological disorders, is defined as a disorder of the reflex motor functions that are provided by various structures of the nervous system.

The pathologies of movement may involve lesions of subcortical motor nuclei, the cerebellum, the pyramidal system, the reticular formation of the brain stem, innervating the skeletal muscles of the peripheral nerves, motoneurons and their processes (axons) involved in conducting nerve impulses.

Epidemiology

According to clinical statistics, peripheral motor neuropathy in diabetes mellitus develops over time in six out of ten patients with this disease.

The human immunodeficiency virus, according to the Journal of Neurology, causes neuropathic conditions in a third of patients, and multiple motor neuropathy is detected in three people per 100,000 of the population and almost three more often affect males.

The most common hereditary disease of the peripheral nerves - Charcot-Marie-Tuta disease - affects about one person in 2.5-5 thousand.

In North America, spinal muscular atrophy annually affects one child from 6-8 thousand babies. According to some information, one of 40-50 people is an asymptomatic carrier of this disease, that is, it has a defective gene that can be transmitted to its children as an autosomal dominant trait.

[1], [2], [3], [4],

Causes of the motor neuropathy

In many cases, the causes of motor neuropathy are  motor neuron diseases. These nerve cells are divided into superior (in the brain) and lower (spinal) cells; the former transmit nerve impulses from the nuclei of the sensorimotor cortex to the spinal cord, and the latter transmit them to the synapses of the muscle fibers.

With degenerative changes of the upper motoneurons, primary lateral sclerosis and hereditary spastic paraplegia are noted. In degenerative lesions of spinal motoneurons, focal syndrome of spinal motor neuron or  amyotrophic lateral sclerosis syndrome, multiple motor neuropathy and distal spinal amyotrophy develop. Also distinguished are etiologically homogeneous syndromes: Verdnig- Hoffman (starts in children up to six months), Dubovitsa ( starts at 6-12 months ),  Kugelberg-Welander (may appear between 2 and 17 years),  Friedreich's ataxia  (manifested by the end of the first decade of life or later). In adults, the most common type of spinal amyotrophy is slowly progressive Kennedy disease (also called spin-bulbar muscle atrophy).

Motor neuropathy is interrelated with degeneration of the cerebellum, which controls muscle tone and coordination of movements. It manifests itself as a hereditary movement disorder or ataxia, as a symptom of multiple sclerosis, as a neurological consequence of an acute violation of cerebral circulation, for more details see.  Ischemic neuropathy

Movement disorders can occur in case of oncological diseases, in particular, in the form of Eaton-Lambert paraneoplastic neurological syndrome. Cm. -  Causes of cerebellar ataxia.

Patients who have suffered cranio-cerebral traumas or poisonings with various toxic substances often come across as impaired motor functions as a neurological complication. Infected with infectious diseases, among the causative agents of which the polyomavirus is noted, the viruses Varicella and Herpes zoster, Human immunodeficiency virus (HIV), Cytomegalovirus, and also the bacteria Borrelia burgdorferi, Mycoplasma hominis, Campylobacter jejuni, Treponema pallidum (causing neurosyphilis)

[5], [6], [7], [8], [9]

Risk factors

Among the risk factors for motor neuropathy, experts refer to disorders of the immune system with activation of autoimmune reactions, loss of the myelin sheaths of nerve fibers and axons of motoneurons.

Elderly people, alcohol-dependent children, children in families with hereditary neurological disorders, cancer patients with lymphomas and lung cancer tumors, most patients after cancer treatment with ionizing radiation and cytostatics are at risk. Details in the article -  Polyneuropathy after chemotherapy

The risk of neurological movement disorders in diabetics is extremely high. Motor neuropathy in diabetes mellitus is discussed in detail in the publication -  Diabetic Neuropathy

Other diseases with motor neurological complications are celiac disease, amyloidosis, megaloblastic anemia (vitamin B12 deficiency), lupus erythematosus (SLE).

Consider the risk when using certain medications that may cause impaired sensory-motor functions. For example, this means Disulfiram (anti-alcoholism), Phenytoin (anticonvulsant), anticancer drugs (Cisplatin, Vincristine, etc.), the drug for hypertension Amiodarone, etc.

[10], [11], [12], [13]

Pathogenesis

In cases of hereditary spinal amyotrophy, the pathogenesis lies in the degeneration of spinal motor neurons and the brain stem region, which occurs due to mutations of the SMN1 gene in the 5ql3 locus encoding the SMN protein complex of motoneuron nuclei, a decrease in which leads to the death of these cells. Perhaps the development of amyotrophy due to defects of the motor nuclei of the cranial nerves and effector nerve endings (neuromuscular synapses). Muscle weakness - with a decrease in their tone, weakening of tendon reflexes and possible atrophy - may be due to the limited release of motor neuron axons into the synaptic cleft of the acetylcholine mediator.

The pathophysiological mechanisms of immunologically caused neuropathies include aberrant cellular and humoral immune responses. Thus, the development of multifocal and axonal motor neuropathy is associated with the formation of IgM antibodies to the myelin sheaths of motor neuron axons and peripheral nerves. The composition of the myelin contains gangliosides GM1, GD1a, GD1b - complex compounds of sphingolipids and oligosaccharides. It is assumed that antibodies are produced by the GM1 ganglioside and can interact with it, activating the immune system of the complement and blocking the ion channels. Since GM1 levels are higher in the axons of motor neurons than in the membranes of sensory neurons, the fibers of the motor nerves are likely to be more susceptible to autoantibody attack.

Also read -  Chronic inflammatory demyelinating neuropathy.

[14], [15], [16], [17], [18]

Symptoms of the motor neuropathy

Different types of motor neuropathy demonstrate some similar manifestations characteristic of disorders of motor function.

Localization and etiology of the disease determine the early symptoms. For example, the first signs of amyotrophic lateral sclerosis are manifested by progressive weakness and stiffness of the arms and legs, which leads to dysbasia - slow walking with poor coordination of movements and balance (a person often stumbles on level ground).

In hereditary spinal muscular atrophy  in adults,  symptoms of motor neuropathy  include  periodic twitching of the superficial muscle fibers (fasciculation) against the background of their reduced tone and weakened tendon reflexes. At a later stage - as the disease progresses - muscle movement limiting movement begins to be felt not only in the arms and legs, but also in other muscle groups (including intercostal respiratory, pharyngeal, orofacial). Because of this, there are problems with breathing, progressing to respiratory failure, and dysphagia (difficulty swallowing). It also slows down and becomes slurred speech. The list of typical symptoms of Kennedy's disease - with genetically determined degeneration of motoneurons in the spinal cord and brainstem - lists the weakness and atrophy of the muscles of the limbs, face, pharynx, larynx and oral cavity. Speech disorders (dysarthria) and swallowing (dysphagia) are noted.

Multiple or multifocal motor neuropathy manifests itself as a unilateral violation of the movement of the limbs, without sensory symptoms. In eight cases out of ten, the disease begins at 40-50 years of age. Most often affected are the ulnar, median and radial nerves with weakness in the hands and wrists, which impedes fine motor skills. Lewis-Sumner syndrome is distinguished, which is essentially a multiple motor-sensory neuropathy of acquired (inflammatory) character with paresthesia of the upper limbs and a decrease in skin sensitivity of the backs of the hands. More information in the article -  Neuropathy of the upper limbs

Motor neuropathy of the lower extremities, as a widespread type of neurological disorder, is discussed in detail in the publication -  Neuropathy of the legs

Some immunologically related neuropathies can have acute and chronic forms. Acute axonal motor neuropathy due to dysfunction of neuronal processes is still diagnosed as a subtype or a variant of Landry-Guillain-Barre polyneuropathy or  Guillain-Barre syndrome  (acute polyradiculoneuritis) - with symptoms in the form of progressive muscular weakness of the distal upper extremities, the fascismus, and anesthesia of the distal parts of the upper extremities, the fascismus. Restrictions on eye movement, lethargic tetraplegia (paralysis of all limbs) in the absence of a conduction block of nerve impulses. Signs of demyelination and sensory impairment in this pathology are absent.

Chronic idiopathic axonal motor polyneuropathy is a frequent neurological disorder in older people (over 65), which manifests itself with symmetrical distal symptoms in the lower limbs in the form of ankle clonus, muscular weakness and restraint of walking, painful cramps of the calf muscles (krampi) in a state of movement, walking, painful cramps of the calf muscles (crampy), and the constraint of movement when walking, painful cramps of the ankle muscles, and weakness and stiffness during walking, and painful cramps in the condition of the ankle, muscle weakness, and stiffness during walking cramps in the front of the tibial muscles after walking.

Due to pathological processes that lead to the violation of certain sections of the myelin sheaths of the processes of motor neurons (as well as the roots and fibers of the spinal nerves that innervate muscles), motor axonal-demyelinating neuropathy can develop with symptoms such as. Involuntary twitching of the muscles of the extremities, their paresthesia (tingling and numbness), impaired tactile and temperature sensitivity (especially of the hands and feet), paresis (partial paralysis), paraplegia (simultaneous paralysis of both arms or both legs), orthostatic dizziness, dysbasia and dysrhea. Vegetative symptoms may manifest by increased sweating and acceleration / deceleration of the heart rate.

Forms

When efferent (motor) and afferent (sensory) neurons and nerve fibers lose their ability to transmit signals, which most often happens in children and adolescents with  hereditary neuropathies  , peripheral motor-sensory neuropathy is diagnosed, which is divided into several types of genetically determined diseases.

Motor-sensory neuropathy type 1 - hypertrophic-demyelinating, which accounts for half of all inherited peripheral neuropathies in children - is associated with segmental demyelination due to impaired synthesis of myelin proteins due to gene mutations on chromosomes 17p11.2, 1q21-q23 and 10q21.

This type of pathology, in which hypertrophy of peripheral nerves is noted, is a slowly progressive atrophy of the peroneal (peroneal) muscles of the lower extremities - type 1 Charcot-Marie-Tout disease. When it muscles of the legs atrophy below the knee in the ankle area (with the formation of a pathologically high arch of the foot and a characteristic change in the shape of the toes); often, when tension occurs, tremor; anhidrosis (lack of sweat) and progressive hypesthesia, and in some cases, loss of pain sensation (in the distal lower extremities); tendon reflexes of the Achilles ligament disappear; signs of mental and mental disorders appear; rarely the disease is accompanied by nervous deafness. In the later stages, the muscles of the arms below the elbow with deformity of the hands also atrophy.

Hereditary motor-sensory neuropathy type 2 (Charcot-Marie-Tuat disease type 2) - axonal amyotrophy, that is, associated with dysfunction and degeneration of processes of motor and sensory neurons without loss of the myelin sheath - affects the same muscle group, manifests from 5 to 25 years. At the same time, mutations were detected on chromosomes 1p35-p36, 3q13-q22 and 7p14.

On the background of almost normal speed of nerve impulses (compared with the first type of the disease), clinical manifestations of distal muscular weakness and atrophy are less pronounced; muscle atrophy below the knee symmetrical in 75% of patients; typical first signs are weakness of the feet and ankles, reduction of tendon reflexes with weakness of the dorsiflexia of the foot in the ankle. There is mild sensory symptoms; there may be pain, sleep apnea, restless legs syndrome, depressive state. Atrophy of the muscles of the hands is rarely observed.

[19], [20], [21], [22], [23]

Complications and consequences

Previously, neuropathologists believed that motor neuron disease did not affect brain function, but research results demonstrated the fallacy of this opinion. It turned out that the negative consequences and complications of amyotrophic lateral sclerosis and degenerative changes in the lower motoneurons in almost half of the patients are manifested by these or other disorders of the central nervous system, and in 15% of cases there is a development of frontotemporal dementia. Changes in personality and emotional state can occur with bouts of uncontrollable crying or laughter.

Violation of contractions of the primary respiratory muscle (diaphragm) causes breathing problems in amyotrophic lateral sclerosis; patients also have increased anxiety and sleep disturbances.

Complications of the axonal-demyelinating form of neuropathy manifest as impaired intestinal motility, urination, and erectile dysfunction.

Damage to the sensory nerves can lead to the loss of pain sensitivity, and neglected injuries and wounds due to infectious inflammation are fraught with the development of gangrene and sepsis.

In case of Charcot-Marie-Tut disease, the joints cannot react normally to the pressure force, which causes microcracks in the bone structures, and destruction of the bone tissue leads to irreversible deformation of the extremities.

Spinal amyotrophy is considered the second most significant cause of infant mortality in the world. If the degree of pathology is insignificant, the patient survives - most often with the subsequent loss of the ability to move independently.

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Diagnostics of the motor neuropathy

At an early stage, neurological movement disorders are difficult to diagnose because their symptoms are similar to the symptoms of other conditions, such as multiple sclerosis, neuritis, or Parkinson's disease.

Diagnosis begins with the examination and testing of tendon reflexes. Laboratory studies are required: biochemical and general blood tests, plasma creatinine phosphokinase level analysis, plasma C-reactive protein, antibodies level (in particular, GM1 ganglioside antibodies), C3 complement, etc. If necessary, the analysis of cerebrospinal fluid is taken.

The main instrumental diagnostics used in neurology include: stimulation electromyography (EMG); electroneuromyography (ENMG); myelography; Ultrasound and MRI scans of the brain (to rule out stroke, cerebral neoplasia, blood circulation problems, or structural abnormalities); positron emission tomography (PET).

Some motor neuropathies are classified as variants of amyotrophic lateral sclerosis, but differential diagnosis is necessary. Among neuropathies of immune genesis with destruction of the myelin sheaths, multifocal motor neuropathy and chronic immune demyelinating polyneuropathy should be differentiated.

Loss of the lower motor neurons with the involvement of sensory nerves must be distinguished from paraneoplastic encephalomyelitis and sensory ganglionic syndromes.

In addition, it is necessary to eliminate myopathic syndromes and muscular dystrophies, for which muscle research is carried  out, as well as Morvan's disease (syringomyelia) - with the help of MRI of the spine, which visualizes the spinal cord.

[28], [29], [30], [31], [32], [33],

Treatment of the motor neuropathy

Neuropathologists admit that today only symptomatic treatment of motor neuropathy is possible, facilitating the condition of patients and somewhat slowing the progression of pathological processes. And for the treatment of hereditary motor and sensory neuropathies of drugs does not yet exist.

One of the generally accepted methods is periodically conducted plasmapheresis, by means of which autoantibodies are removed from patients' blood.

In multiple motor neuropathy, human immunoglobulin (IVIg) is infused; glucocorticoids (Prednisolone or Methylprednisolone) can be used systemically, providing immunomodulatory effects. For all types of movement disorders, vitamins A, D and groups B are prescribed.

Some other medications are also used. First of all, for oral administration, normalizing tissue metabolism and L-carnitine repairing damaged cells are prescribed: adults in the form of capsules (0.25-0.5 g twice a day), children in the form of syrup (the dose is determined by the doctor depending by age).

To increase the conductivity of nerve impulses, the CNS stimulating inhibitor of the enzyme Ipidacrine cholinesterase (other trade names - Neuroimin, Amipirin, Axamon) is used orally or parenterally: adults - 10-20 mg three times a day (or 1 ml intramuscularly); Only oral administration is allowed for children from one year to 14 years old - a single dose is 10 mg (half a pill) - up to three times a day. The course of treatment lasts one and a half months; Ipidacrine may be reappointed two months after the end of the first course.

This drug is contraindicated in disorders of heart rate, inflammatory gastroenterological and pulmonary diseases and pregnancy. And as its most likely side effects, nausea, diarrhea, dizziness, drooling, bronchial spasms are noted.

Recently, foreign neurologists in patients with amyotrophic lateral sclerosis prescribe a new drug (FDA approved) Riluzole (Rilutec). Its effectiveness and even the mechanism of action are still poorly understood, and a number of serious side effects are noted in the list of complications of its use.

Useful information from the material -  Treatment of diabetic neuropathy  and publication -  Treatment of neuropathy of the upper limbs

Treatment of hereditary motor-sensory disorders requires the participation of not only a neurologist, but also a physiotherapist. Physiotherapy can play an important role in slowing and preventing disease progression and managing symptoms, and the treatment plan should focus on strengthening the affected muscle group. This may be a therapeutic massage, exercise therapy, ultrasound, electrical stimulation, water treatments, pelotherapy, etc.

Many patients need help from an orthopedist: orthopedic shoes or ankle and foot orthoses are necessary to maintain the arch when walking; often you can not do without crutches, walking sticks or walkers; some need a wheelchair.

And in cases of severe limb deformities, surgical treatment is undertaken.

Those who prefer alternative treatments are advised to use bee venom - bee sting  treatments.

However, it should be borne in mind that the effectiveness of the poison of honeybees (with its active substance melittin) has been proven only in peripheral neuropathies caused by chemotherapy.

But from paresthesia for movement disorders, massage with chamomile and lavender essential oils (a few drops on a dessert spoon of the essential oil) helps.

In the same way, herbal medicine helps with neuropathies induced by the use of anticancer drugs. Used medicinal plants such as:

• Salvia officinalis (Salvia officinalis), which contains apigenin, which has significant antioxidant activity and protects the nerve cells of the peripheral nervous system;
• calamus acorus (Acorus calamus), which extract anesthetizes, soothes and relieves seizures;
• Ginkgo biloba (Ginkgo biloba) containing terpenic trilactones, which have a positive effect on damaged neurons.

In case of progressive spinal amyotrophy, homeopathy can also be applied, recommending to such patients the drugs Argentum nitricum, Plumbum, Phosphorus, Kali phosphoricum, Cuprum, Arnica montana. But they are also not able to help with genetically "programmed" pathologies that cause impaired motor functions.

Prevention

It is impossible to prevent hereditary spinal amyotrophy or immune-mediated demyelination of motor neurons and their axons.

The question of their prevention is genetic counseling for families in which there are carriers of abnormal genes. To do this, a blood test is performed, and antenatal screening can be performed, that is, a survey of a pregnant woman using chorion biopsy (CVS).

More information in the article -  Genetic analysis during pregnancy

[34], [35], [36], [37], [38], [39]

Forecast

The prognosis of the development of the disease depends on the cause of motor neuropathy, the degree of damage to the structures that provide nerve signals and reflex motor functions of the central nervous system.

Very often, these diseases are rapidly progressing, and the functional defect is so significant that patients become disabled.

Hereditary motor-sensory neuropathies do not reduce life expectancy, but comorbidities cause various complications of neurological disorder.

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