What Are Motor Neuron Diseases?

Motor neuron disease (MND) is a group of chronic progressive neurodegenerative diseases of unknown etiology that selectively invade spinal cord anterior horn cells, brainstem motor neurons, cortical pyramidal cells, and pyramidal tracts. The incidence is about 1 to 3 / 100,000 per year, and the prevalence is 4 to 8 / 100,000 per year. Since most patients die within 3 to 5 years after the onset of symptoms, the prevalence of the disease is close to the incidence. The etiology of MND is unclear, and it is generally believed that it is caused by the exposure of genetically susceptible individuals to adverse environments with increasing age, that is, genetic factors and environmental factors jointly lead to the occurrence of motor neuron disease.

Basic Information

English name

motorneurondisease

English alias

MND

Visiting department

Neurology

Common symptoms

Muscle weakness, muscle atrophy, muscle bundle tremor, increased muscle tone, etc.

Contagious

no

Causes of motor neuron disease

The etiology of MND is unclear, and it is generally believed that it is caused by the exposure of genetically susceptible individuals to adverse environments with increasing age, that is, genetic factors and environmental factors jointly lead to the occurrence of motor neuron disease.

Genetic factor

More than a dozen mutation genes related to the pathogenesis of ALS have been found, the most common of which is the superoxide dismutase 1 gene (SOD1), followed by FUS and TARDBP, and the rest also include ALS2, SETX, VAPB, ANG, OPTN, ATXIN2 and so on. But the first three genes are related to most ALS, while the remaining large numbers are only related to a few ALS. All familial ALS mutation genes can appear in patients with sporadic ALS. The only clinical identification point of the two groups is that the former is younger, about 10 years earlier than the latter, and the first-degree relatives of patients with sporadic ALS. The increased risk of ALS and other neurological degenerative diseases cannot be ruled out that genetic factors also play a role in sporadic ALS. These mutation genes related to the pathogenesis of ALS include SOD1, Alsin gene, TARDNA binding protein gene, sarcoma fusion gene (FUS / TLS), VAMP-related protein type B gene (VAPB), angiopoietin gene (ANG), and Ataxin-2. (ATXN2), ubiquitin protein 2 gene (UBQLN2), C9orf72-related ALS, etc.

2. Environmental factors

Based on a large number of epidemiological investigations, many environmental factors related to the onset of ALS have been found, including heavy metals, pesticides, herbicides, trauma, diet and exercise. But in general, there is a lack of connection between these factors, and whether they are necessarily related to the occurrence of ALS and the mechanism that they lead to ALS needs to be further confirmed. The environmental factors related to the onset of ALS are agricultural labor and rural life, electric shock, ionizing radiation, trauma, excessive exercise, smoking, industrial raw materials, heavy metals, etc.

Clinical manifestations of motor neuron disease

1. According to different clinical manifestations, motor neuron disease can generally be divided into the following four types:

(1) Amyotrophic lateral sclerosis (ALS).

(2) Progressive muscle atrophy (PMA).

(3) Progressive bulbar palsy (PBP).

(4) Primary lateral sclerosis (PLS).

Regardless of the initial form of onset, ALS, PMA, PBP, and PLS are now considered related disease entities. PMA and PBP usually eventually progress to ALS. Whether motor neuron disease is a single cause and has a different phenotype is not completely clear, but ALS is certainly the most common and easily recognized phenotype among them. Therefore, in various studies of this disease, ALS is also used to represent the group of MND diseases.

2. ALS can be divided into the following two types according to whether they have family inheritance:

(1) Sporadic ALS (sALS), no family history of ALS;

(2) Familial ALS (fALS). There are more than one ALS patients in the family. According to the different genetic methods, familial ALS can be divided into autosomal dominant inheritance, autosomal recessive inheritance, and X-associated inheritance.

ALS is most common in adults. The average age of sporadic patients is 56 years, and the average age of patients with positive family history is 46 years. The average course of the disease is 3 to 5 years, but the course of disease of patients with different subtypes also varies. Generally speaking, patients who are younger than 55 years of age have a longer survival. In addition, familial ALS patients have a different disease course than sporadic patients and are associated with specific gene mutations. However, no matter what type of ALS patients, they eventually die of respiratory failure.

The main manifestations of ALS above and below the clinical motor nervous system include muscle weakness, muscle atrophy, muscle bundle tremor and increased muscle tone, hypertenoid reflex, and positive pathological signs. Generally there are no paresthesias and urination disorders. Among them, muscle weakness, muscle atrophy, and muscle bundle tremor are the manifestations of lower motor nervous system involvement; increased muscle tone, hypertenoid reflexes, and positive pathological signs are the main manifestations of upper motor nervous system involvement. For diagnosis purposes, the skeletal muscle of the whole body is usually divided into four segments from top to bottom according to the site, namely: the ball, neck, chest and lumbosacral segments, in order to find evidence of damage to the upper and lower motor neurons in the above four parts. .

For different patients, the first symptoms can have multiple manifestations. Most patients develop onset with asymmetrical local limb weakness, such as walking stiff, walking, falling easily, and inflexible finger movements (such as holding chopsticks, opening doors, and fastening). It can also cause onset of bulbar symptoms such as dysphagia and dysarthria. A few patients develop symptoms with respiratory symptoms. With the progress of the disease, muscle atrophy, "muscle jumping" (muscle tremor), cramps, and cramps spread to other muscles throughout the body. In the later stages of the disease, except for eye movements, all motor systems in the body are affected, affecting breathing. Muscles, dyspnea and respiratory failure. Most patients eventually die of respiratory failure or other complications. Because the disease mainly affects the motor nervous system, there is generally no paresthesia and dysuria during the course of the disease. Statistics show that the onset site is more common in patients with limb weakness, and a small number of patients start with dysphagia and dysarthria. Different disease subtypes have different onset sites, course of disease, and speed of disease progression.

Cognitive impairment is a common feature of ALS. Frontotemporal dementia (FTD) is a coexisting disease in patients with ALS. According to statistics, about 5% of ALS patients meet the diagnostic criteria of FTD, while 30% to 50% of ALS patients do not meet the diagnostic criteria of FTD, but they also show signs of executive function decline. For ALS patients with advanced cortical dysfunction such as cognition or behavior, but who do not meet the FTD diagnostic criteria, if the behavior change is the main manifestation, it is called "ALS with behavior disorder (ALSBi)" The main manifestation is called "ALS with cognitive dysfunction (ALSci)". The clinical manifestations of patients with FTD include: loss of attention, executive dysfunction, decreased ability to plan and solve problems, fluent or non-fluent aphasia, personality changes, irritability, and decreased intelligence. Or affected slightly. Currently, there is no reliable screening test for cognitive impairment in ALS. Speech fluency is a sensitive indicator, and frontal lobe executive function should also be screened.

Motor neuron disease test

1. Cerebrospinal fluid examination is basically normal.

2. The electromyography showed that the spontaneous generation potential was normal, and the nerve conduction velocity was normal.

3. Muscle biopsy showed neurogenic muscle atrophy.

4. Head and neck MRI can be normal.

Motor neuron diagnosis

The diagnostic criteria of ALS mainly rely on the clinical manifestations and auxiliary examination results such as electromyography and the clinical manifestations for diagnosis.

The Chinese Medical Association Neurology Branch has proposed the diagnostic criteria (draft) of amyotrophic lateral sclerosis in China with reference to the diagnostic criteria of the World Federation of Neurology. content include:

1. Must have the following neurological symptoms and signs: the characteristics of lower motor neuron damage (including normal clinical manifestations and abnormal electromyography of muscles); signs of upper motor neuron damage; the disease gradually progresses.

2. According to the above three characteristics, the following three degrees of diagnosis can be made: In the muscle group of 4 areas of the ALS (bulb, neck, chest, lumbosacral innervation zone), 3 areas have upper and lower motor nerves Symptoms and signs of neurological damage; The proposed ALS has symptoms and signs of upper and lower motor neuron damage in 2 areas; It is possible that ALS has symptoms and signs of upper and lower motor neuron damage in 2 areas, or 2 Symptoms and signs of lesions in the upper motor neurons were found in ~ 3 areas.

3. The following supports the diagnosis of ALS: one or more muscle bundle tremors; electromyography suggests neurogenic damage; motor and sensory nerve conduction velocity is normal, but the distal motor conduction latency can be extended and the amplitude is low; None Conduction block.

4. ALS should not have the following symptoms and signs: signs of sensory disturbances; obvious sphincter dysfunction; visual and ocular muscle movement disorders; autonomic dysfunction; symptoms and signs of extrapyramidal diseases; symptoms of Alzheimer disease And signs; ALS ALS-like syndrome symptoms and signs that can be explained by other diseases.

The above diagnostic criteria are helpful for the clinical diagnosis of ALS, but it should be noted that the formulation of the criteria is based on research and clinical drug trials rather than clinical practice, so the criteria are stricter and are not conducive to the early diagnosis of the disease. In clinical work, attention should be paid to distinguish ALS from diseases caused by other causes, especially some treatable diseases, in order to maximize the benefits for patients.

Motor neuron disease treatment

1. Vitamin E and Vitamin B group are taken orally.

2. Coenzyme intramuscular injection, citicoline choline intramuscular injection and other treatments can be applied intermittently.

3. For muscle cramps, diazepam can be taken orally, clonoxybutyric acid, and in divided doses.

4. Some drugs that can be used in the treatment of this disease, such as thyroid-stimulating hormone-releasing hormone, interferon, lecithin, testosterone, cysteine, immunosuppressive agents, and plasma exchange therapy, etc., but it is still difficult to determine whether they are effective. Evaluation.

5. In recent years, with the development of stem cell technology, stem cell therapy has become one of the treatments for this disease, which can alleviate and improve the condition.

6. Massage the affected limb, passive movement.

7. For those who have difficulty swallowing, use nasal feeding to maintain nutrition and water intake.

8. Respiratory muscle paralysis, assisted breathing with a ventilator.

9. Prevention and treatment of lung infections.