OVERVIEW
Amyloidotic peripheral neuropathies are a group of severe progressive sensory and motor peripheral neuropathies with autonomic dysfunction caused by the deposition of amyloid from different sources in the peripheral nerves. This group mainly includes familial amyloidosis polyperipheral (FAP), acquired polypoidal peripheral neuropathy, and sporadic amyloid neuropathy.
Etiology
Acute and chronic infections, inflammation, tumors, viruses, gene mutations and long-term hemodialysis.
Symptoms
1. Familial amyloidosis polyperipheral neuropathy (FAP)
(1) FAP type I (Portuguese type)
The disease starts at the age of 25-30 years, and the clinical symptoms are sensory impairment of the limbs (trophic ulcers may appear in the area of sensory loss), extensor paralysis, foot drop, and loss of tendon reflexes of the limbs. Pupillary changes, impotence and azoospermia occur with autonomic nerve involvement. In advanced renal involvement, proteinuria and renal failure occur. In addition, some patients may develop hypoplasia of various endocrine glands, cerebral nerve damage, cerebellar and pyramidal fasciculus damage, and so on.
(2) FAP type II (Indian/Swiss type)
FAP II (Indian/Swiss type) starts after 50 years of age and is more serious in males than in females. It manifests as carpal tunnel syndrome, which progresses slowly and develops into generalized peripheral neuropathy in 5-10 years, accompanied by foot drop, peroneal atrophy, vitreous clouding, hepatosplenomegaly without renal function impairment and sphincter dysfunction.
(3) FAP type III (Iowa type)
FAP III (Iowa type) starts after the age of 40, and the manifestations of peripheral nerve damage are similar to those of FAP I. It is often accompanied by severe gastrointestinal symptoms and nephropathy.
(4) FAP Type IV (Finnish type)
FAP type IV (Finnish type) starts at the age of 30 years, with dystrophy, ulceration and chronic glaucoma in the lattice cornea at the initial stage, and cerebral nerve involvement as well as sensory and autonomic nerve damages gradually appearing after the age of 50 years. In addition, there can be skin relaxation, thickening and proteinuria.
(5) FAP type V (other types)
Danish type: 40 to 50 years of age onset of disease, mainly manifested as dyspnea, mild sensory impairment, rapid progression of heart failure, no other peripheral nerve signs. Italian type: manifestation of heart disease, multiple peripheral neuropathy.
2. Acquired polypoidal peripheral neuropathy
(1) Immune cellular: primary amyloidosis neuropathy, the disease develops in old age, the main clinical features are fine sensory fiber neuropathy and autonomic hypofunction. The main clinical features of this disease are fine sensory fiber neuropathy and autonomic hypofunction, which are characterized by abnormalities of painful sensation, symmetrical loss of pain and temperature sensation, and preservation of positional sensation and vibration sensation. Sensory symptoms may be followed by muscle weakness, initially confined to the feet and progressively involving the upper extremities, similar to the clinical picture of carpal tunnel syndrome. Autonomic hypofunction may appear at the beginning of the disease, manifested by upright hypotension, diarrhea, impotence, skin ulcers and loss of sweating function.
(2) Tumor-associated adrenaloid tumor: often accompanied by sensorimotor polyneuropathy, manifested by hypotonia, poor distal sensation, loss of reflexes and autonomic symptoms.
(3) Reactive: secondary amyloid neuropathy, which is now more common in chronic rheumatic diseases, and occasionally also produces peripheral nerve amyloidosis.
3. Sporadic amyloid neuropathy
It is not easy to distinguish from other types, mainly by immunohistochemical examination.
Examination
1. Blood tests
Including blood glucose, liver function, kidney function, blood sedimentation routine examination; rheumatism series, immunoglobulin electrophoresis, cryoglobulin, M protein and other autoimmune related serological examination.
2. Serum heavy metal test
Including (lead, mercury, arsenic, thallium, etc.) concentration test.
3. Urine examination
Including urine routine, this – week protein, urine porphyrin and urinary excretion of heavy metals.
4. Tissue biopsy
Nerves, skin, rectum and other parts of the biopsy microscopically visible amyloid deposition of peripheral nerves.
5.Genetic examination
DNA restriction fragment length analysis and DNA probe technology can be used to examine all types of abnormal DNA fragments and detect asymptomatic carriers.
Diagnosis
The diagnosis of the disease relies on tissue biopsy to detect amyloid deposits, and frequent sites of sampling include the peroneal nerve, muscle, skin, rectum, and lingual muscle. DNA analysis reveals mutations in the transthyretin gene that are helpful in the diagnosis and staging of FAP. Most primary amyloid neuropathies have M protein detected by immunofixation electrophoresis of serum or urine, the latter of which is helpful in the diagnosis.
Treatment
There is no effective treatment, and the principles of treatment for amyloidosis include the following:
1. Reduce the synthesis of precursor proteins that cause amyloid.
2. Inhibiting the synthesis of amyloid fibers.
3. inhibiting extracellular deposition of amyloid.
4. promote dissolution of formed deposits.
5. Symptomatic treatment with high doses of B vitamins, adenosine triphosphate (ATP), coenzyme A, and inosine may have a promoting effect on the repair and functional reconstruction of neural tissue. The traditional mafaram prednisone regimen (MP) whose experience comes from the treatment of amyloidosis of the hematopoietic system, is ineffective in treating amyloidosis, is effective in only a small percentage of patients, and often causes abnormal bone marrow proliferation or leukemia with serious side effects such as infection. Immunosorption of abnormal proteins and plasma exchange have also achieved some efficacy in a few patients with FAP.