Demyelination refers to a kind of disease in which myelin sheath is lost or thinned and axons are relatively intact. Pathological changes are demyelination of nerve fibers, while nerve cells remain relatively intact, which affects the transmission of nerve impulses. Acute demyelinating nerve myelin regeneration is rapid and complete, which has little effect on functional recovery. Chronic demyelinating neuropathy, due to repeated demyelination and myelination, regenerated nerve membrane cells proliferate obviously, nerves become thicker, axons are lost, and functional recovery is incomplete.
Symptomatic characteristics
① Acute or subacute onset; ② The clinical symptoms are severe, but the imaging lesions are relatively small; ③ MRI of spinal cord showed that the focus was multicentric, the central canal of spinal cord was not obviously dilated, and the focus was patchy enhanced or not enhanced; Sometimes MRI examination of the head finds paraventricular or brainstem lesions; ④ The effect of hormone therapy is obvious; ⑤ There is a history of optic neuritis or myelitis in the past, and MRI follow-up of spinal cord is of great value to suspicious patients. The most common clinical disease is multiple sclerosis.
Disease classification
Different scholars have different classifications of demyelinating diseases. According to the damage degree of myelin sheath itself or other tissue structures (bystander effect), it can be divided into primary and secondary. Myeloslysis refers to the destruction of normal myelin, while myelination disorder refers to the abnormality of enzymes needed for myelin metabolism, also known as leukodystrophy. There are also classification methods of inflammatory demyelination and non-inflammatory demyelination.
1.Etiological classification 1.Sehaumburg According to the etiology, Sehaumburg divides demyelination into five categories: viral, immune, hereditary (myelination), toxic (or nutritional) and traumatic.
2.Olekmj is effective in treating autoimmune diseases, acute disseminated encephalomyelitis, acute hemorrhagic leukoencephalitis, multiple sclerosis, infection, progressive multifocal leukoencephalopathy, toxic (or metabolic), carbon monoxide poisoning, vitamin B ~ (12) deficiency, mercury poisoning (Minamata disease) and alcohol (or tobacco). Marcea's Fava-Bigger nano-syndrome, hypoxia, radiation or vascular injury, Binswanger's disease, inherited diseases of myelin metabolism, adrenal leukodystrophy, metachromatic leukodystrophy, krabbe's disease, Alexander's disease, canavan-Van disease, bogart-Bertrand disease, Pelizza-Merzbach disease, phenylketonuria, etc.
3. Allen classification (Allen ⅳ. Neuropathology in Greenfield, edward arnold. London, 1992: 447-520).
(1) Acute disseminated encephalomyelitis: classic (infectious, after vaccination, idiopathic) and hyperacute (acute hemorrhagic leukoencephalitis).
(2) Multiple sclerosis: classic type (Charcot type), acute type (Marburg type), extensive type (Schilder type), centripetal type (Balo type) and neuromyelitis optica (Devic type).
Multiple sclerosis is the most common demyelinating disease in clinic. Because of multifocal sclerosis, the clinical symptoms are complex and mixed type is not uncommon. Early symptoms usually manifest as an attack-remission process. Sometimes patients will automatically recover (or basically recover) without treatment, and then with the delay of time, the disease will enter an irreversible stage, thus causing acute attacks of multiple sclerosis. Patients may have systemic symptoms, including visual impairment, bladder-rectum and sexual dysfunction, and motor symptoms (such as muscle weakness and spasm). ), sensory symptoms (such as numbness, irritability, false feeling, etc. ), brain symptoms (such as tremor and ataxia) and other symptoms (such as fatigue, cognitive impairment and mental syndrome). ). According to the lesion site, it is generally divided into the following four types.
1. Spinal cord type mainly involves lateral bundle and posterior bundle. When a single large plaque or multiple plaques are fused, one side or a certain segment of the spinal cord can be injured, which shows semi-transverse or transverse spinal cord injury. Patients often complain of back pain first, followed by central paralysis of lower limbs, sensory impairment below the damage level, urinary retention and impotence. When the posterior bundle of cervical spinal cord is damaged, the patient's head flexion can cause radiation shock-like numbness or pain from the upper back to the lower limbs, which is Lhermitt sign. Tonic spasms and painful seizures that spontaneously and briefly spread to one side or both sides from a certain part of the trunk and limbs can also occur, which are called tonic painful spasms.
2. Optic nerve spinal cord type is also called optic neuromyelitis and Devic disease. The first symptom of this type can be optic nerve and chiasma injury, or spinal cord injury, which can be separated by months or even years. It is not uncommon for both to be damaged at the same time. The onset can be acute or slow. Patients with optic nerve injury show pain during eye movement, decreased vision or complete blindness, normal or pale optic disc, and frequent binocular injury. Optic chiasma lesions are mainly visual field defects. Patients with optic disc inflammation have obvious optic disc edema besides decreased vision. The manifestations of spinal cord injury are the same as those of spinal cord type.
3. Brain stem cerebellar type is characterized by dizziness, diplopia, nystagmus, unclear pronunciation, central or peripheral facial paralysis, pseudobulbar paralysis or paralysis, cross paralysis or hemiplegia, exercise ataxia, limb tremor and dance.
4. Brain types are mainly characterized by hemiplegia, aphasia and mental disorders, such as emotional instability, involuntary crying, paranoia, stupor and mental retardation, which are rare in clinic. [ 1]
pathological change
Classical MS lesions are widely distributed, which can involve the brain, brain stem, spinal cord, optic nerve and other parts, among which white matter, especially ventricular angle or ventricular white matter, is the most prominent, but gray matter can also be involved. Lesions are round or plastic, with different sizes, ranging in diameter from 0. 1cm to several centimeters, and the number varies. Fresh lesions are reddish or translucent, while old lesions are gray and hard.
The early stage usually begins with perivenous demyelination (also known as perivenous demyelination), accompanied by infiltration of perivascular monocytes or lymphocytes. A large number of monocytes often infiltrate at the edge of progressive demyelinating lesions, where myelin degenerates and disintegrates into particles, which are swallowed by phagocytes to form foam cells. Most axons are preserved, and some axons may swell, twist, break or even disappear due to degeneration. In addition, oligodendrocytes decreased significantly or even disappeared; The reactive proliferation of astrocytes is very obvious, and sometimes obese cells can appear. The advanced lesions become gelatinous and sclerotic spots.
If demyelinating areas and myelinated areas alternate to form concentric circles, it is called concentric sclerosis, also known as Barlow's disease, and sporadic cases have been reported in northeast and southwest China. In recent years, it has been observed that concentric sclerosis and general demyelinating lesions can appear in the same case; Therefore, Balo's disease may only be the manifestation of a certain stage of classical Schilder's disease, which is characterized by extensive fusion demyelination of subcortical white matter. The myelin sheath of subcortical arcuate fibers is well preserved.
In some cases, the lesions mainly involve the spinal cord and optic nerve, causing visual impairment and spinal cord symptoms, also known as neuromyelitis optica, which is common in the Far East. There are reports of Devic diseases involving only spinal cord in China.
Etiology and pathogenesis
The etiology is unknown, which may be related to the following factors: ① Genetic factors: There are more HLA-A3, -B7 and -DW2 antigens in white patients in Europe and America. ② Man-made and geographical factors: This disease is more common in cold temperate zone than tropical zone. The prevalence rate in Europe is high, while the prevalence rate in East Africa and Africa is low. ③ Infection factors: It was suspected that measles virus, herpes virus and HIV virus were related to this disease, but even if molecular biology methods were used to detect the virus genome in the focus and surrounding brain tissues, a clear conclusion could not be drawn.
Animal experiments show that injection of brain tissue components or rabies vaccine can cause demyelinating lesions, suggesting that this disease may be an allergic disease induced by many factors. CD4T (helper) and CD8T (suppressor) cells can be detected in demyelinating lesions, but the exact pathogenesis is still unclear. [2]
Demyelinating disease refers to demyelinating areas with different sizes on the inner surface of the central nervous system. This actually includes three situations: the first is demyelination caused by axonal injury; The second is that myelination is defective and normal development cannot be completed, which is called leukodystrophy. This disease is mostly genetic defect and is only found in children. The third type is myelin sheath damage, and axons are not damaged or slightly damaged. Lesions are divided into acute and chronic: acute lesions are common in large demyelinating necrosis of subcortical white matter, with a large number of lattice cells, mostly concentrated near blood vessels. Chronic diseases often show complete brain structure, from partial demyelination or thinning to complete demyelination. Multiple sclerosis is prone to demyelinating diseases of the central nervous system in young adults, and genetic factors have certain influence on the occurrence of this disease. According to the different parts of the lesion, different symptoms appear.
The nervous system consists of neurons. Neurons can be divided into cell bodies and cell processes. The cell body has a nucleus and cytoplasm surrounding the nucleus, and the cell processes have axons and dendrites. Axons usually form nerve fibers, and myelin sheath is wrapped around myelinated nerve axons, which is formed by the cell membrane of myelinated cells, which are oligodendrocytes in the central nervous system and Schwann cells in peripheral nerves. Demyelinating disease is an acquired disease. Its etiology and clinical manifestations are different, but it has similar characteristics. Its pathological changes are demyelination of nerve fibers and relatively intact nerve cells. The role of myelin sheath is to protect neurons and make nerve impulses transmit quickly on neurons, so the loss of myelin sheath will affect the transmission of nerve impulses. Nerve myelin sheath in acute demyelinating diseases can be completely regenerated quickly. Although the regenerated myelin sheath is thin, it generally has little effect on functional recovery. Chronic demyelinating neuropathy, due to repeated demyelination and regeneration of myelin sheath, Schwann cells proliferate obviously, nerves thicken, axons are lost, and functional recovery is incomplete. The probability of headache in demyelinating diseases is not high, but demyelinating patients also have headaches. There are two reasons: ① nerve stimulation symptoms, normal nerve fibers, nerve endings and cell bodies have sensory impulses, and cell bodies have motor impulses; In diseased nerve fibers, impulses can occur in the middle of axons and pass to the periphery and center. This ectopic impulse can be caused by increased sensitivity and sensitivity to mechanical stimulation, or it can spontaneously follow the normal impulse of the same fiber or the stimulation can cause repeated excitement at the affected part, which can cause pain. ② Demyelination is accompanied by the infiltration of lymphocytes, plasma cells and polymorphonuclear leukocytes, which forms a serious inflammatory reaction and even stimulates the meninges, leading to increased intracranial pressure and headache.