Amyloid peripheral neuropathy
Introduction
Introduction to amyloidosis peripheral neuropathy Amyloidosis peripheral neuropathy refers to amyloidotic peripheral neuropathy of peripheral nerves, which is a group of severe progressive sensations caused by amyloid deposition in peripheral nerves, motor peripheral neuropathy, and autonomic dysfunction. This group of diseases mainly include familial amyloidosis polyneuropathy (FAP), primary light chain amyloidosis, and dialysis related/beta2-microglobulinamyloidosis. basic knowledge The proportion of illness: the incidence rate is about 0.005%-0.007% Susceptible people: no special people Mode of infection: non-infectious Complications: glaucoma
Cause
Causes of amyloidosis peripheral neuropathy
(1) Causes of the disease
In 1885, the pathologist Virchow first used the term amyloid in the observation of waxy liver. It was found that the waxy substance in the liver was stained with iodine and sulfuric acid, which was considered to be a kind of polysaccharide cellulose, so it was called amyloid. Amyliod, it is now clear that the so-called amyloid is a -pleat sheet configuration in which the soluble protein forms a -pleat sheet under the action of some pathological factors such as the cell agonistic factor produced by the mononuclear phagocytic system. It becomes an insoluble protein and deposits outside the cells of multiple organs or tissues. Therefore, amyloid is also called amyloid. There are two types of amyloid deposited in peripheral nerves. Transthyretin, mainly synthesized by the liver, can also be produced in the choroid plexus and eyes of the central nervous system. It is a kind of plasma transport protein, transporting thyroxine and vitamin A. The deposition of transthyroid protein is found in FAP. An amyloid protein is the light chain (kappa chain and lambda chain) of immunoglobulins produced by plasma cells and found in primary light chain amyloidosis and plasma cell hyperplasia. In addition, there are diabetes-related islet amyloid chains, apolipoprotein series, serum amyloid A and glial proteins. Amyloid proteins deposited in the central nervous system include amyloid and prion. The former is mainly found in Alzheimer's disease (AD), the latter found in pruritus, mad cow disease and CJD occurring in humans.
(two) pathogenesis
In recent years, the molecular pathological mechanism of FAP has been further understood, and FAP is classified into five types according to gene defects or gene products (amyloid).
Although it can be determined that the deposition of amyloid in the extracellular space leads to structural and functional abnormalities of tissues and organs such as peripheral nerves, the exact pathological mechanism is not clear.
Autopsy revealed that amyloid deposits can be deposited in a variety of tissues and organs. The most frequently invaded tissues are the vessel wall and its surroundings, the intima and adventitia of the peripheral nerves, the posterior root ganglia, the thyroid, the heart conduction tissue and the tongue muscle. Amyloid staining by Congo red, observed under polarized light microscope, showing special green fluorescence, sural nerve biopsy, electron microscopic observation of amyloid as a 7nm diameter non-branched long fiber, often deposited in the interstitial nerve (neural Membrane and outer membrane) and its nourishing blood vessels, also found in the basement membrane of Schwann cells, using anti-TTR and anti--LC antibodies for immunohistochemical staining, can identify the nature and type of amyloid.
The pathological changes of peripheral nerves are characterized by demyelination and axonal degeneration, and the number of myelinated and unmyelinated fibers is reduced.
Prevention
Amyloidosis peripheral neuropathy prevention
There is no effective preventive method to strengthen the care and symptomatic treatment of the sick, which can prolong the survival period.
Complication
Amyloidosis peripheral neuropathy complications Complications glaucoma giant tongue
Different types of different systemic involvement may have different manifestations, such as endocrine gland dysfunction, hepatosplenomegaly, proteinuria or nephropathy, abnormal globulinemia, chronic glaucoma and giant tongue.
Symptom
Symptoms of amyloidosis peripheral neuropathy Common symptoms Hypotension Proteinuria Amyloidosis Sensory disorder Diarrhea Muscle atrophy Hepatosplenomegaly
The disease includes multiple clinical types, which are mainly classified according to the ethnicity of the affected family.
In recent years, with the progress of molecular biology research, it is now possible to classify according to the characteristics of gene mutations. The corresponding relationship between the two classifications is shown in Table 1. FAP is autosomal dominant, but different types of clinical characteristics are different. .
1. FAPI type (Portuguese type): 25 to 30 years old, characterized by sensorimotor peripheral neuropathy, early manifestations of bilateral lower extremity involvement, foot drop, late involvement of upper limbs, manifested as motor impairment of extremities, paralysis reflex disappeared .
When the autonomic nerve is involved, pupillary changes occur, impotence and azoospermia, dystrophy can cause skin ulcers, late kidney involvement, proteinuria and renal failure, and various endocrine gland dysfunction, cranial nerve damage, cerebellum and Cone beam damage and so on.
2. FAPII type (North American/Irish type): It is a late-type hair style of FAPI type, and its clinical features are severe sports peripheral neuropathy and cardiomyopathy.
3.FAP type III (Indian/Swiss type): Onset after 50 years of age, it is a sensorimotor type of peripheral neuropathy. The initial manifestation is carpal tunnel syndrome. Later, the lower extremities are gradually involved, and the foot ptosis and calf muscle atrophy occur. Some patients have obvious Symptoms of fasciculation and bulbar palsy, in addition to crystal opacity and hepatosplenomegaly.
4. FAPIV type (Iowa type): Onset after 40 years of age, peripheral nerve damage is similar to FAPI type, accompanied by severe gastrointestinal symptoms and renal disease.
5. FAPV type (Finnish type): It is a disease at 30 years of age. The initial manifestation is lattice corneal dystrophy, ulcer and chronic glaucoma. After 50 years of age, cranial nerve involvement and sensory and autonomic nerve damage gradually occur. There may also be skin loosening, thickening and proteinuria.
6. Primary amyloidosis neuropathy: also known as non-familial amyloidosis neuropathy, 10% to 30% of primary light chain starch degeneration can be combined with peripheral neuropathy.
The disease is characterized by senile disease. The main clinical features are small-fiber sensory neuropathy and autonomic dysfunction. It is characterized by painful paresthesia, symmetry pain and temperature sensation, and positional and vibratory retention. Muscle weakness can occur after feeling the symptoms, beginning to be limited to the feet, and gradually affecting the upper limbs, similar to the clinical manifestations of carpal tunnel syndrome.
Low autonomic function can occur at the beginning of the disease, manifested as orthostatic hypotension, diarrhea, impotence, skin ulcers and sweating loss. Other systems may have hepatosplenomegaly, proteinuria or nephropathy, abnormal globulinemia and Giant tongue.
Examine
Amyloidosis peripheral neuropathy
1. Blood test: including blood sugar, liver function, kidney function, routine examination of erythrocyte sedimentation rate; rheumatism series, immunoglobulin electrophoresis, cryoglobulin, M protein and other serological tests related to autoimmunity.
2. Detection of serum heavy metals (lead, mercury, arsenic, antimony, etc.).
3. Urine examination: including urine routine, this-week protein, urinary porphyrin and heavy metal excretion in urine;
4. Cerebrospinal fluid: In addition to cerebrospinal fluid routine examination should also check immunoglobulin.
5. Electromyography and neurophysiological examination.
6. Tissue biopsy (including skin, sural nerve, muscle, rectum and tongue).
Diagnosis
Diagnosis and differentiation of amyloidosis peripheral neuropathy
The diagnosis of this disease mainly relies on tissue biopsy to find the deposition of amyloid. The frequently used materials include the sural nerve, muscle, skin, rectum and tongue muscle.
DNA analysis found that transgenic protein gene mutations contribute to the diagnosis and classification of FAP. 90% of primary amyloidosis neuropathy can be detected by immunofixation electrophoresis in serum or urine. The latter has a diagnosis. help.
Isolated amyloidosis peripheral neuropathy is difficult to diagnose and should be differentiated from a variety of other peripheral neuropathies. At this time, sural nerve biopsy is particularly important.
