What Is Neuralgic Amyotrophy?

Hereditary neuromuscular atrophy (Peronial myoatrophy), also known as Charcot-Marie-Tooth disease (CMT), Hereditary Motor and Sensory Neuropathy (HMSN), is a chronic progressive neuromuscular atrophic disease. There is often a family genetic history, so it is also known as peroneal muscular atrophy, which belongs to the category of hereditary motor sensory neuropathy (HMSN). According to the pathological changes and nerve conduction velocity measurement results, they are divided into HMSN and HMSN .

Hereditary neuromuscular atrophy

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Hereditary neuromuscular atrophy (Peronial myoatrophy), also known as Charcot-Marie-Tooth disease (CMT), Hereditary Motor and Sensory Neuropathy (HMSN), is a chronic progressive neuromuscular atrophic disease. There is often a family genetic history, so it is also known as peroneal muscular atrophy, which belongs to the category of hereditary motor sensory neuropathy (HMSN). According to the pathological changes and nerve conduction velocity measurement results, they are divided into HMSN and HMSN .

Chinese name

Hereditary neuromuscular atrophy

Foreign name

peronial myoatrophy

Attributes

disease

Aka

Hereditary motor sensory neuropathy

Classification

HMSN and HMSN

Hereditary motor sensory neuropathy is a group of the most common familial

Hereditary neuromuscular atrophy

peroneal myoatrophy

Charcot-Marie-Tooth disease; hereditary motor sensory neuropathy

Neurology> Nervous System Hereditary Diseases

G72.8

In 1886, Charcot and Marie were in France, and Tooth had reported the disease in the United Kingdom, so it was named Charcot-Marie-Tooth disease (CMT). The disease is found in countries around the world, with a prevalence of about 40 per 100,000.

80.9% of the diseases are single-gene hereditary diseases, and sporadic cases account for about 20%. Autosomal dominant inheritance is most common, followed by autosomal recessive inheritance and X-linked inheritance.

CMT1 is autosomal dominant or recessive, but autosomal dominant is most common. About 60% onset before the age of 10, more common in men.

CMT2 is autosomal dominant, and the age of onset is relatively late, with an average age of 25 years. Compared with CMT1 type, the incidence of CMT2 type is low (about 1/3 of CMT1 type).

CMT3 is also known as Dejerine-Sottas syndrome, which also includes congenital hypomyelinicneuropathy. This type of disease is rare, accounting for only about 1% of all CMT patients.

CMT4 is also called hereditary ataxia polyneuritis or Refsum disease. It is autosomal dominant. Infant onset is from late infancy to early childhood, and adult onset is from 10 to 30 years old.

CMT is mostly autosomal dominant inheritance, a small part is autosomal recessive inheritance, X chromosome linked dominant inheritance and X chromosome linked recessive inheritance.

With the development of molecular biology technology, people have a deeper understanding of the molecular pathological mechanism of CMT. CMT is usually divided into 4 types based on clinical manifestations, genetic patterns and pathological characteristics.

There have been 4 types of peripheral myelin proteins related to CMT: peripheral myelinic protein 22 (PMP22), myelinic protein zero (MPZ), connexin 32 (ligandin32, li32), early growth Response gene (earlygrowthresponsegene, EGR). There is no definite correspondence between genetic defects or abnormalities of myelin proteins and the clinical phenotype of CMT. The same type of myelin protein abnormalities can occur in different types of CMT. Conversely, the same type of CMT can have multiple myelin proteins abnormal. The cause of this genotype, gene product, and clinical type heterogeneity is unclear. The quantitative effect of genes can explain why mutations in the same gene can cause different types of myelin proteins. For example, the normal human PMP22 gene is 2 copies, clinically asymptomatic, when the gene mutation is 3 copies, the clinical manifestation is CMT1, when the mutation is 1 copy (with 1 copy of the gene fragment missing), the clinical manifestation is stress-prone Peripheral neuropathy.

CMT4 type is a phytanic acid storage disease, also known as Refsum disease, which is a type of peroxidative body disease. Peroxisome is a kind of single-layer membrane organelle. It exists in all cells except mature red blood cells. There are more than 40 catalase or other oxidases in its matrix. Its main function is to catalyze ultra-long-chain fatty acids, Oxidation of alkanoic acids and hexahydropyridine carboxylic acids, synthesis of plasmalogens, cholesterol and bile acids, and degradation of prostaglandins and ethanol. Phytanic acid storage disease is due to reduced phytanic acid--hydroxylase activity in the peroxidized small body, which prevents phytanic acid from -oxidation and accumulates in the body, which can enter the lipid membrane of the tissue and interfere with its function And cause disease.

In addition, there are CMT5, CMT6, CMT7 and CMT-X4 clinical variants. CMT5 is autosomal dominant or recessive, with clinical manifestations of muscle atrophy and spastic paraplegia; CMT6 is CMT with optic nerve atrophy; CMT7 is CMT with retinal pigment degeneration. These three types of linked genes and corresponding gene products are currently unavailable. Not sure. CMT-X refers to CMT with X-linked dominant or recessive inheritance.

CMT1 and CMT3 have similar peripheral neuropathological characteristics, which are mainly manifested by chronic demyelinating processes, that is, myelinated fibers show demyelinating, thin myelinating, and myelinating regeneration, accompanied by Schwann (Schwann) cell proliferation , Onion-like hypertrophy, collagen fibers hyperplasia, collagen sac formation. Interstitial blood vessel changes are more obvious, mainly due to endothelial cell proliferation and increased swallowing vesicles (Guo Yuzheng, 1992). Autopsy pathology revealed that the anterior horn cells and posterior root ganglion cells of the spinal cord were reduced or disappeared, and the number of myelinated fibers in the thin bundle of the upper cervical spinal cord was also reduced.

The pathological characteristics of CMT2 are significantly different from the previous two types, mainly manifested by chronic axonal mutation and reduced number of myelinated fibers, thick myelinated fibers are more severe, and occasional secondary segmental demyelination, without beaded pulp Characteristics of acute axonal degeneration such as globular formation and phagocytic cells engulfing myelin. Unmyelinated fibers also show axonal mutation and reduced numbers, with occasional regenerated fibers. No nerve hypertrophy, collagen fibrosis, and collagen capsule formation.

CMT4 autopsy revealed a diffuse nodular hypertrophy of the peripheral nerve from the nerve root to the nerve endings. Microscopic examination showed nerve axis mutation and demyelination. Schwann cells and collagen fibers proliferated to form an onion-like structure. Schwann cells Crystal-like inclusions can be seen inside.

Occurs in children or adolescents. There are more men than women and progress is slow. In most patients, muscle atrophy and weakness begin with the distal lower limb muscles (fibula, extensor toes, and small foot muscles), and gradually develop upward and symmetrically. A few patients can also start with the hand. Muscle atrophy often has clear boundaries. The lower extremity does not exceed the lower third of the thigh, which is exactly like an "upside down wine bottle" (called "crane leg"). Due to muscle atrophy, arched foot, foot drop, and horseshoe varus deformity can occur, but the muscle strength is still relatively good, and is not proportional to muscle atrophy. Upper-extremity muscle atrophy usually begins with small hand muscles, but usually does not exceed the lower third of the forearm. Extremity tendon reflexes weaken or disappear, and Achilles tendon reflexes are more common. May have extremity cuff dysfunction, accompanied by autonomic dysfunction such as rough skin, cold extremities, less sweat or cyanosis, and occasional changes such as optic nerve atrophy, retinal degeneration and nystagmus. The above clinical manifestations are often typical CMT1 patients. Patients with autosomal recessive inheritance may be accompanied by changes in ataxia, scoliosis, and so on.

Electrophysiological examination of 1/3 patients showed that the duration of fibrillation wave, positive sharp wave, and action potential was prolonged, and the motor conduction speed was significantly slowed down to 10-20m / s, and the sensory conduction speed was also slowed down, especially with gastrocnemius nerve involvement. protruding.

Roussy-Lévy syndrome was first reported by Roussy and Lévy in 1926. Its clinical characteristics are similar to Friedreich's ataxia and CMT. It develops during infancy or after birth. It first affects the lower limbs and manifests as mild distal weakness, which gradually affects the upper limbs later. . The sensory disorders are more severely damaged by position and vibration, often accompanied by obvious sensory ataxia without cerebellar signs. Distal muscle extremities atrophy, high arches, posterior scoliosis deformities, and tendon reflexes disappear. Electrophysiological examination showed a slowing of nerve conduction. Nerve biopsy pathology was consistent with changes in demyelinating peripheral neuropathy. The disease is benign development, can still walk at 70 years old.

Roussy-Lévy syndrome has long been classified as a spinal cerebellar degeneration disease. In recent years, molecular biology studies have shown that the disease and CMT1 gene defects are exactly the same, both located at 17p11.2. Combining electrophysiological changes and pathological characteristics of peripheral nerve biopsy, it is now clear that Roussy-Lévy syndrome should be classified as demyelinating CMT, that is, CMT1 type.

The genetic characteristics and clinical manifestations of CMT2 and CMT1 are very similar, but the autosomal dominant inheritance of CMT2 is relatively young, with an average age of 25 years. Compared with CMT1 type, the incidence of CMT2 type is low (about 1/3 of CMT1 type), sensory symptoms are relatively mild, upper limbs are rarely affected, peripheral nerves are not thick, arched feet are rare, the disease progress is relatively slow, and There is a platform period. Electrophysiological examination showed that the motor conduction velocity was normal or only slightly slowed down, most often not less than 38-40 m / s.

CMT3 is also known as Dejerine-Sottas syndrome, which also includes congenital hypomyelinicneuropathy. This type of disease is rare, accounting for only about 1% of all CMT patients. Infants and young children develop onset, the child has retarded growth and development, weakness and atrophy of the distal lower extremities, and later the upper limbs are gradually involved. Gloves and sock-like sensory disturbances were found on the distal limbs, and some patients had pain and numbness in their feet. Skeletal deformities such as arched feet and scoliosis can occur early. Before 10 years of age, most of the superficial superficial nerves can be touched, especially the ulnar nerve, median nerve, and common peroneal nerve. Cerebral nerve involvement is common, manifested as nystagmus, deafness and facial paralysis. Due to lack of proprioception, ataxia is present in almost all cases.

CMT4 is also called hereditary ataxia polyneuritis or Refsum disease. It is autosomal dominant. Infant onset is from late infancy to early childhood, and adult onset is from 10 to 30 years old. Peripheral nerve damage is characterized by symmetrical motor sensory neuropathy in the distal limbs, manifested by distal muscle weakness and sensory disturbances. Tendon reflexes weaken or disappear. A few patients feel the symptoms are not obvious. Visual involvement is manifested by vision loss, night blindness, retinal pigment degeneration, reduced vision, abnormal pupils, and cataracts. Most patients have myocardial damage, but also neurological deafness, loss of smell, cerebellar ataxia, skeletal deformity, keratosis, or ichthyosis. Infants can also have convulsions and hypotonia. Cerebrospinal fluid protein is significantly increased, generally 1 ~ 3g / L, sugar and chloride content and cell number are normal. Serum phytanic acid levels also increased significantly, fatty acids increased by 10% to 20%. Blood cholesterol, HDL and LDL are moderately reduced. Electrophysiological examination of the nerve showed a decrease in peripheral nerve conduction velocity.

CMT3 type can appear skeletal deformities such as arched feet and scoliosis. CMT4 type visual impairment is manifested by vision loss, night blindness, retinal pigment degeneration, reduced vision, abnormal pupils, and cataracts. Most patients have myocardial damage, which can cause sudden death due to acute heart failure caused by heart damage. There may also be neurological deafness, loss of smell, cerebellar ataxia, skeletal deformity, skin keratosis or ichthyosis. Infants can also have convulsions and hypotonia.

1. Most of the cerebrospinal fluid examination is normal, and a few may have increased protein content. Electromyographic examination showed denervated changes in atrophic muscles, nerve conduction velocity (NCV) in the extremities slowed down or even disappeared, lower limbs were more pronounced than upper limbs, and motor nerve conduction speeds were significantly changed than sensory nerve conduction speeds. In familial cases, NCV changes are similar in the same family, and there are many differences in different families. Some patients have abnormalities in visual, auditory, and somatosensory evoked potentials, suggesting involvement of the central nervous system.

2. Serum protein electrophoresis should be performed routinely for idiopathic peripheral neuropathy of unknown cause.

3. Serum phytanic acid levels may be significantly increased, and fatty acids may be increased by 10% to 20%. Blood cholesterol, HDL and LDL are moderately reduced.

4. Using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) combined with DNA sequence analysis to detect point mutations in genes.

5. Muscle biopsy Muscle biopsy shows neurogenic muscle atrophy. Peripheral nerve changes of nerve biopsy CMT1 type are mainly demyelination and Schwann cell proliferation to form "onion" -like changes; CMT2 type is mainly axonal mutation.

Patients with X chromosome-linked dominant inheritance have abnormal brainstem auditory evoked potentials and visual evoked potentials, and the central and peripheral conduction velocity of somatosensory evoked potentials has slowed down.

Electrophysiological examination of the nerves shows that motor and sensory nerve conduction velocity is slow, which is an important electrophysiological feature of the disease. The peripheral nerve conduction velocity (NCV) of infants is more than 60% below normal, and the NCV of infants older than 3 years is less than 38m / s. CMT type II peripheral nerve action potential amplitude <80% of the lower limit of normal, nerve conduction velocity in the lower limit of normal value or slightly slowed.

The diagnosis of hereditary motor sensory peripheral neuropathy mainly depends on hereditary family history, clinical characteristics, neurophysiological examination and nerve biopsy. Where conditions permit, molecular genetic analysis can also be used for diagnosis.

Chronic motor sensory neuropathy that occurs in children or adolescents should consider the possibility of this disease. According to the onset of adolescent onset, progressive distal lower limb muscle atrophy and a special distribution form (limited to the lower 1/3 of the thigh, showing "Crane legs"), but the muscle strength is relatively good, tendon reflexes are often weakened or disappeared, telescopic sensory disorders and other characteristics, the diagnosis is not difficult, a positive family history can help confirm the diagnosis.

For suspicious patients, special attention should be paid to observation of high arch and toe deformation, and abnormal neurological enlargement. Ask family members for paresthesia in the distal limbs. Physical examination should be performed on all family members if necessary. The determination of serum phytanic acid level can provide an important basis for the diagnosis of CMT4 type.

Hereditary neuromuscular atrophy should be distinguished from chronic inflammatory demyelinating polyneuropathy (CIDP), distal spinal muscular atrophy, and distal progressive muscular dystrophy.

1. Chronic progressive distal spinal muscular atrophy The muscle atrophy and weakness of the disease and the course of the disease are similar to those of CMT, but the sensory function is not involved, and EMG shows anterior horn damage. Generally, muscle atrophy begins with the distal ends of the upper limbs and gradually develops into the forearms, upper arms, and lower limbs. There is no clear boundary, and it is often not accompanied by telescopic dysfunction.

2. Chronic Guillain-Barré syndrome progresses relatively quickly, most of the muscle atrophy is mild, protein-cell separation can be seen in CSF, and prednisone treatment is better.

3. The clinical manifestations of distal myodystrophy are similar to those of CMT type II, but myocardial electromyography shows that myogenic damage can be identified.

4. Familial amyloid polyneuropathy is indistinguishable from clinical and CMT, and requires nerve biopsy or DNA analysis. .

5. Chronic polyradiculoneuritis has sympathetic lower motor neuron paralysis and telescopic sensory disturbance in the limbs, but the atrophic muscle lacks the distribution characteristics of CMT disease, and muscle atrophy is consistent with muscle weakness.

There is currently no special treatment for hereditary neuromuscular atrophy, mainly symptomatic treatment. Neurotrophic drugs such as B vitamins, vitamin E, citicoline, ATP, coenzyme A, and nerve growth factors can be selected to promote the improvement of nerve function. Those with foot drop or horseshoe deformity can perform orthopedic surgery or wear orthopedic shoes and perform functional training of the limbs. Keep your limbs warm and avoid heavy physical labor.

The natural course usually progresses slowly, but does not affect life. Because the patient's proximal muscles are less affected, they rarely lose their ability to walk completely. CMT4 type can use diet therapy to limit the intake of phytanic acid to reduce peripheral nerve and cerebellar symptoms and prevent the disease from progressing. Milk, beef tallow, eggs, and vegetables and fruits with more chlorophyll contain higher phytanic acid, so you should limit your intake.

The prognosis of hereditary neuromuscular atrophy is generally good, the course of the disease is extremely slow, and it can still survive for decades after the onset of disease. This disease can cause sudden death due to acute heart failure caused by heart damage.

Prenatal check, first determine the parent's genotype, and then use fetal villi, amniotic fluid or umbilical cord blood to analyze the fetal genotype, make a prenatal diagnosis, in order to terminate the pregnancy in time. Careful investigation of his family tree should be performed as early as possible on the neurophysiological examination and sural nerve biopsy of suspicious cases.

Collagen, Vitamin E, Citicoline, CoA