What Is Neuromyelitis Optica?
Optic neuromyelitis (Nuromyelitis optica, NMO) is an acute or subacute demyelinating lesion of the optic nerve and spinal cord at the same time or sequentially. The disease was first described by Devic (1894). It is clinically characterized by acute or subacute onset of blindness in one or both eyes. It is accompanied by transverse or ascending myelitis in the first or subsequent days or weeks. It is called Devic disease or Devic syndrome. Data show that NMO accounts for 1% -22% of all demyelinating diseases, a low proportion in Western countries and a high proportion in non-Caucasians.
- Western Medicine Name
- Optic neuromyelitis
- English name
- neuromyelitis optica, NMO
- Affiliated Department
- Internal Medicine-Neurology
- Whether to enter health insurance
- Yes
| Dong Huiqing | (Chief physician) | Department of Neurology, Xuanwu Hospital, Capital Medical University |
| Zhang Jihong | (Resident) | Department of Neurology, Xuanwu Hospital, Capital Medical University |
- Optic neuromyelitis (Nuromyelitis optica, NMO) is an acute or subacute demyelinating lesion of the optic nerve and spinal cord at the same time or sequentially. The disease was first described by Devic (1894). It is clinically characterized by acute or subacute onset of blindness in one or both eyes. It is accompanied by transverse or ascending myelitis in the first or subsequent days or weeks. It is called Devic disease or Devic syndrome. Data show that NMO accounts for 1% -22% of all demyelinating diseases, a low proportion in Western countries and a high proportion in non-Caucasians.
- On May 11, 2018, the National Health Committee and other five departments jointly formulated the "First Batch of Rare Diseases", and optic neuromyelitis was included. [1]
Classification of optic neuromyelitis diseases
Optic myelitis
- (1) Single-phase NMO: 10-20% [2] , which is relatively common in Europe. The lesions are limited to the optic nerve and spinal cord. Optic neuritis is mostly bilateral and simultaneous with or similar to myelitis (within 1 month). Neurological dysfunction is often heavier than recurrent NMO. But the survival time is longer. [3]
- (2) Recurrent NMO: 80% -90% [3] , it is relatively common in Asia, and most often present as simple isolated optic neuritis or solitary myelitis, with only about 10% of patients with concurrent onset of optic nerve and spinal cord for the first time [2] ] .
- (3) Progressive NMO: Rare.
Optic neuromyelitis optic neuromyelitis spectrum disease
- There are some non-specific inflammatory demyelinating diseases with a pathogenesis similar to NMO, and their NMO-IgG positive rates are also higher. Wingerchuk summarized it and proposed the concept of neuromyelitis optica Spectrum disorders (NMOSDs) [4] . In 2010, the European Federation of Neurology (EFNS) clearly defined NMOSDs, specifically referring to a group of potential pathogenesis similar to NMO, but with limited clinical involvement and not fully in line with NMO-diagnosed related diseases [5] .
- (1) 2010 EFNS NMOSDs [5]
- Types of affected site limitations, such as longitudinally extensive transverse myelitis (LETM), recurrent isolated optic neuritis (RION), and bilateral optic neuritis (BON).
- NMO occurs in the context of organ-specific or non-organ-specific autoimmune diseases.
- Atypical cases with symptomatic or asymptomatic brain lesions.
- Optic-spinal MS (OSMS) in Asian countries.
- (2) 2007 Wingerchuk NMOSDs
- NMO.
- Lesions are limited to the optic nerve and spinal cord.
- a) Idiopathic single-phase or recurrent long-segment transverse inertial myelitis (MRI lesions 3 vertebral segments).
- b) Optic neuritis: Recurrent optic neuritis or concurrent bilateral optic neuritis.
- Asian type optic spinal cord multiple sclerosis (OSMS).
- Optic neuritis or long-segment transverse inertial myelitis with autoimmune diseases.
- Intracranial lesions of the optic neuritis or myelitis with NMO characteristics (hypothalamus, corpus callosum, peripheral ventricle, and brain stem).
- One study showed that 55% of NMO-IgG-positive patients with transmyelitis relapse or develop NMO within 1 year.
Causes and pathogenesis of optic neuromyelitis
- The cause is unknown.
- AQP4 is the main aquaporin of the central nervous system and is located on the foot processes of astrocytes. AQP4 is the main target of NMO-IgG, which explains that the lesions of NMO are mainly located in the optic nerve and spinal cord. The AQP4 antibody enters the central nervous system through the passageable part of the blood-brain barrier, immediately encounters astrocytes and causes a cell-dependent cytotoxic response. The astrocyte foot processes are degraded by NMO-IgG and complement, and then activated Macrophages, eosinophils, and neutrophils produce cytokines, oxygen free radicals, etc., which cause blood vessel and parenchymal damage, eventually leading to damage to white matter and gray matter, including axon and oligodendrocytes.
- Familial NMO cases are rare, accounting for less than 3% of all diagnosed NMOs. Human leukocyte antigens DPB1 * 0501 (Asian population) and DRB1 * 0301 (Caucasian population) are associated with NMO susceptibility. This shows that heritage factors play a role in the pathogenesis of NMO.
Optic neuromyelitis pathophysiology
- NMO lesions mainly affect the optic nerve, optic cross, and spinal cord (thoracic and cervical). The pathological changes are related to the survival of NMO patients.
Optic neuromyelitis spinal pathology
- (1) Gross pathology: Generally, multiple spinal cord segments are involved, which can usually spread from the thoracic spinal cord to the cervical or lumbar spinal cord. Swelling and softening of the spinal cord can be seen in early fatal cases; in patients with longer survival, the spinal cord can shrink.
- (2) Pathology under the microscope: The swelling and softening of the spinal cord showed that the lesions involved the gray matter and white matter of the spinal cord, necrotic tissue was focal or fused into a sheet, and small cysts were formed, axon and nerve cells were lost, and neutrophils Infiltration, capillary hyperplasia, cuff-like infiltration of lymphocytes around blood vessels can be seen; spinal cords in other parts can be scattered or fused into a piece of demyelination. Cavity formation was observed in the shrinkage site of the spinal cord, interstitial hyperplasia was evident, and Wallerian degeneration of the ascending and descending nerve fiber bundles.
Optic neuromyelitis
- Optic nerve inflammation includes lymphocyte, macrophage, monocyte infiltration, and vascular inflammation. After a long time, necrosis and cavity formation, proliferation of vascular endothelial cells, proliferation or loss of glial cells, and demyelination of the optic nerve and optic cross can be seen. Retrograde axonal injury results in loss of the retinal nerve fiber layer.
Optic neuromyelitis other
- Some parts of the central nervous system in some NMO patients, such as the brainstem, periventricular area, and semi-oval central white matter, can appear like classic MS-like demyelinating lesions.
Clinical manifestations of optic neuromyelitis
- Limited epidemiological data show that the prevalence of NMO is 0.3-4.4 / 100,000, and the annual incidence is 0.05-0.4 / 100,000. Both men and women can develop the disease, and the single-phase NMO has the same prevalence in men and women. The incidence of recurrent NMO in women is significantly higher than that in men [2] , and the prevalence of women / men is about 9-12: 1. The average age of onset is 30-40 years, and about 10% of NMO patients are younger than 18 years.
- NMO mainly has two major symptoms of the optic nerve and spinal cord, and some patients have symptoms of brain stem damage. Approximately half of the patients develop with isolated optic neuritis, of which 20% have bilateral optic neuritis; half of the patients develop with isolated myelitis; and 10% of patients have both the optic nerve and spinal cord involved.
Optic neuromyelitis
- Eye pain, decreased vision or blindness, visual field loss. Can be monocular, binocular interval or simultaneous onset.
Optic myelitis myelopathy
- Transversal inertial spinal cord damage is more common, including deep beam sensations below the corresponding lesion level of the spinal cord, dyskinesia and bladder and rectal dysfunction, radicular pain, painful spasm, Lhermitte sign, and respiratory muscles in patients with high cervical involvement Paralysis symptoms.
Optic neuromyelitis brain stem symptoms include
- Symptoms such as refractory hiccups, nausea, and vomiting, which are involved in the medulla oblongata junction, are relatively specific in NMO, and some cases are the only first manifestations. Intersexual encephalopathy may cause drowsiness, drowsiness, hyponatremia, etc.
Optic neuromyelitis
MRI Optic neuromyelitis magnetic resonance imaging (MRI)
- 1. Skull MRI: Many NMO patients have brain lesions. The brain lesions of about 10% of NMO patients are consistent with MS. Its distribution is mostly consistent with the high expression area of AQP4, but does not meet the diagnostic criteria of MS imaging. The characteristic lesions are located in the hypothalamus, thalamus, triventricle, aqueduct, pontine cover and around the four ventricles. The bulbar lesions are often associated with cervical lesions. Lesions are often not intensive.
- In addition, pseudotumor-like demyelinating and reversible posterior white matter encephalopathy can also be seen in patients.
- 2. Eye MRI: The optic nerve is thickened and swollen in the acute phase, showing long T1 and long T2 signals, and "track-like" enhancement can be seen. Usually bilateral optic nerves are abnormal, and abnormalities are seen on the optic cross and visual conduction pathways.
- 3. Spinal MRI: The lesion often involves 3 or more vertebral segments, which is the most specific imaging manifestation of NMO. NMO is most common in the cervical or thoracic region, and the lesion can extend upward to the lower part of the medulla. The lesions are mostly located in the middle part of the spinal cord, involving most gray matter and some white matter. The acute phase is often accompanied by swelling of the spinal cord and enhancement is visible. In the later stage of the disease, the spinal cord became thinner, atrophied, and a hollow cavity formed.
Optic neuromyelitis cerebrospinal fluid examination
- Acute neutrophils and eosinophilia are more common in the acute phase, with about 13-35% of patients with cell numbers greater than 50 / mm3. 46-75% of patients with elevated CSF protein. Less than 30% of NMO patients can be positive for cerebrospinal fluid oligoclonal zones.
NMO-IgG Optic neuromyelitis serum NMO-IgG
- NMO-IgG is an immune marker of NMO, and it is one of the important reference basis for distinguishing NMO and MS. It needs to be tested repeatedly. In addition, NMO-IgG patients with strong NMO are more likely to have relapses, and their titer may be used as an indicator of relapse and treatment efficacy. The positive rate is different in different experimental methods. The positive rate of NMO-IgG in serum of NMO patients is about 50-75%. The most sensitive method is cell transfection immunofluorescence.
Optic neuromyelitis serum autoantibodies
- About 40-60% of NMO patients can be positive for antibodies to other autoimmune diseases. Such as antinuclear antibodies, anti-SSA / SSB antibodies, anticardiolipin antibodies, thyroid-related antibodies, acetylcholine receptor antibodies and so on.
Optic neuromyelitis
- 1. Visual acuity: more than 80% of NMO patients are only 20/200 or worse, and more than 30% of patients have no light perception; 30% of patients have less than 20/200 vision after the first onset; In NMO patients, half of the patients have monocular acuity less than 20/200, and 20% of them have reduced binocular visual acuity.
- 2. Visual field examination: NMO patients may have central and peripheral visual field defects.
- 3. Retinal thickness (OCT): The retinal nerve fiber layer (RNFL) in NMO patients is obviously missing, with an average reduction in thickness of approximately 30-40UM, and an average reduction in thickness of MS of 20-30 UM. Ratchford et al. Found that RNFL was reduced by 31 UM in the first episode of NMO-related neuritis and 10 UM in each subsequent episode. RNFL is associated with vision, visual field, functional impairment, and disease progression. Blindness occurs when the average RNFL is below 70 UM.
- 4. Visual evoked potential (VEP): Most patients have abnormal VEP, which is mainly manifested by P100 prolonged latent time, reduced amplitude, or inability to elicit P100. Some patients can find subclinical lesions.
Diagnosis and differential diagnosis of optic neuromyelitis
Optic neuromyelitis diagnosis
- Chinese experts recommend the use of the NMO diagnostic criteria revised by Wingerchuk in 2006 [6] , with sensitivity and specificity of 87.5% and 83.3%, respectively. as follows:
- (1) Necessary conditions (at least one episode of each of the following) Optic neuritis Transverse myelitis.
- (2) Supporting conditions (at least two) MRI: normal or lesions do not meet the diagnostic criteria for multiple sclerosis imaging. Spinal MRI: The lesion has more than 3 spinal segments. NMO-IgG was positive in serum.
- You can diagnose NMO if you have 2 of all the necessary conditions and support conditions.
Differential diagnosis of optic neuromyelitis
- 1. The main points of multiple sclerosis identification are as follows
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- (2) Optic neuritis: multiple lesions in one eye, while NMO often affects both eyes successively, and has spinal cord lesions or obvious remission-relapse.
- (3) Acute myelitis: acute onset, paralysis showed transverse spinal cord injury, no remission and relapse in the course of the disease, and no manifestation of optic nerve damage.
- (4) Leber optic neuropathy, subacute necrotizing myelopathy, subacute combined degeneration, spinal dural arteriovenous fistula, syphilitic optic neuromyelopathy, spinocerebellar ataxia, hereditary spastic paraplegia, spinal tumors, spinal cord Vascular disease, tropical spastic paralysis, hepatic myelopathy, and some connective tissue diseases, such as systemic lupus erythematosus, Behcet's disease, Sjogren's syndrome, systemic vasculitis and other spinal cord injuries should also be noted with NMO Phase identification.
Optic neuromyelitis treatment
/ Optic neuromyelitis acute / relapse treatment
- Glucocorticoid
- The most commonly used first-line treatments are to inhibit the inflammatory response, promote leukocyte apoptosis and inhibit polymorphonuclear leukocyte migration, which can reduce the inflammatory activity and progress of the disease, and protect nerve function. The application principles are: large doses, short courses of treatment, drug reduction is fast first and then slow, and later reduced to small doses and maintained for a long time.
- Specific method: Methylprednisolone 1g, intravenous infusion 1 / day × 3-5 days, 500mg intravenous infusion 1 / day × 3 days, 240mg intravenous infusion 1 / day × 3 days, 120mg intravenous infusion 1 / day × 3 days, 60mg Slowly step down to small doses for long periods of time after oral administration. For hormone-dependent patients, the hormone reduction process is slower, which can be reduced by 5mg per week to the maintenance amount (2-4 tablets per day). Low-dose hormones must be maintained for a long time.
- Hormones have certain side effects, electrolyte disorders, abnormal blood sugar, blood pressure, and lipids, upper gastrointestinal bleeding, osteoporosis, femoral head necrosis, and fat redistribution. During hormone therapy, potassium and calcium supplementation should be paid attention to, and acid suppressants should be applied.
- 2. Plasma exchange (PE)
- Related to the removal of plasma autoantibodies, complements and cytokines. It is effective for patients with severe symptoms and ineffective glucocorticoid treatment. Approximately 50% of patients with ineffective NMO treated with hormone shock are still effective with plasma exchange. The classic treatment regimen is usually to receive 4-7 replacements within 5-14 days, each time about 1-1.5 times the plasma volume. It is generally recommended to replace 3-5 times, each time the amount of plasma exchange is 2-3L, most of them will be effective after 1-2 times.
- 3. Intravenous immunoglobulin, IVIg [7]
- Can be used in patients with acute attacks and poor response to hormones. The dosage is 0.4g / kg / d, intravenous infusion, usually for 5 consecutive days as a course of treatment.
- 4. Hormones in combination with other immunosuppressants
- When hormone shock treatment is not effective, especially patients with other autoimmune diseases, hormones and other immunosuppressive treatment options can be selected. Such as combined with cyclophosphamide treatment, to stop disease progression.
Preventive treatment of optic myelitis in remission
- After treatment in the acute phase, most NMOs can be transferred to the remission phase. Sudden discontinuation of drugs or poor adherence to treatment can easily lead to recurrence of NMO. Early relapsed NMO and NMOSDs combined with serum NMO-IgG-positive patients should be prevented and treated early. The current regimens are azathioprine, morphine mycophenolate, merlot, mitoxantrone, cyclophosphamide, methotrexate, intravenous immunoglobulin and prednisone. Azathioprine, morphicoxol, and rituximab are the most commonly used long-term preventive drugs.
- Interferon [8] , natalizumab [9], and fingolimod [10] may make NMO worse.
- Azathioprine
- It takes 4-6 months for azathioprine to be fully effective, and a small dose of hormone can be used in combination before it is fully effective. For AQP4 antibody-positive patients, immunosuppressants should be applied for a long time to prevent recurrence.
- Usage: Prednisone alone or in combination with 2-3mg / (kg.d) by weight [1mg / (kg.d) by weight], usually prednisone is gradually reduced after azathioprine has taken effect. For AQP4 antibody-positive patients, immunosuppressants should be applied for a long time to prevent recurrence.
- Side effects: fever, nausea, vomiting, decreased white blood cells, thrombocytopenia, gastrointestinal tract, liver damage, myalgia, infection, slightly increased risk of tumors, etc. The blood routine should be monitored weekly at the beginning of the medication treatment, and can be changed to every 2 weeks thereafter, and re-examined once every 1-2 months after stabilization, and liver function should be re-examined every 2-3 months.
- 2. morphine mycophenolate
- It is commonly used in the treatment of azathioprine intolerance. 1 to 3 g / d, orally. Common side effects are gastrointestinal symptoms and increased chance of infection.
- 3. Rituximab
- Rituximab is a monoclonal antibody specific to CD20, which can effectively reduce B lymphocytes and achieve therapeutic purposes. The advantage is fast onset (full effect within 2 weeks), infusion 2 times every six months.
Symptoms and rehabilitation of optic neuromyelitis
- With supportive care, patients' dysfunction can be improved and their quality of life improved. At present, there are no published studies related to symptomatic supportive therapy for NMO, and most of the treatment experience comes from the treatment of MS.
- 1. Painful cramps can be treated with carbamazepine, gabapentin, baclofen and other drugs. For more severe trigeminal neuralgia and neuralgia, pregabalin can also be applied.
- 2. Amitriptyline, selective norepinephrine reuptake inhibitor (SNRI), norepinephrine and specific serotonin antidepressant (NaSSA), pregabalin, etc. can be used for chronic pain and paresthesia. drug.
- 3. Depression and anxiety can be treated with selective serotonin reuptake inhibitors (SSRI), SNRI, NaSSA drugs and psychological counseling.
- 4. For fatigue and fatigue, Modafinil and Amantadine can be used.
- 5. Tremor can be applied with drugs such as benzensol hydrochloride, alorolol hydrochloride and the like.
- 6. Bladder and rectum dysfunction urinary incontinence can choose imipramine, oxybutynin, prazosin, etc .; urinary retention should be intermittent urinary catheterization, laxatives can be used for constipation, and enema can be used in severe cases.
- 7. Sexual dysfunction can use drugs to improve sexual function.
- 8. Cognitive disorders can use cholinesterase inhibitors.
- 9. Difficulty walking can use central potassium channel antagonists.
- 10. Spastic muscle tension increase in the lower limbs can be taken orally by baclofen. In severe cases, it can be administered intraspinally. Botox A can also be used.
- 11. When using high-dose glucocorticoids for limb function training, you should not exercise too much to avoid aggravating osteoporosis and femoral head weight bearing. When reduced to a small dose orally, activities can be encouraged and corresponding rehabilitation training can be performed.
Prognosis of optic neuromyelitis disease
- Ghezzi A et al reported that the annual recurrence rate of NMO was 1.3 ± 1.2, and the proportions of reaching EDSS 3.0 scores at 5 years, 10 years, and 15 years were 65%, 82%, and 86%, respectively; the proportions reaching EDSS 6.0 were 42%. , 53% and 69%; the proportions reaching EDSS 10.0 were 8%, 12% and 23%, respectively. Reaching EDSS 3.0 is related to the age of onset, the interval between the first attack and the second attack, and the recurrence rate. Achieving EDSS 6.0 is related to the underlying EDSS score and relapse rate at the time of onset. Relevant risk factors for recurrent NMO include women, a younger age, onset of dyskinesia during the first episode of myelitis, concomitant autoimmune diseases, and a high frequency of relapses in the first two years of the disease.
Optic neuromyelitis disease care
- Optic myelitis has a long course and is prone to recurrence. Patients and their families should understand the importance of adherence to medication and improve compliance with medication. Try to avoid predisposing factors, such as colds, fever, infections, births, trauma, colds, tooth extractions, overwork, and mental stress. You cannot vaccinate arbitrarily, and strengthen physical function exercises to maintain mobility. With psychological rehabilitation as the guide and functional rehabilitation as the core, patients' confidence to overcome the disease is enhanced, thereby maximizing the quality of life of patients.
Optic neuromyelitis psychological care
- Listen to the patient's report, understand the patient's situation and feelings, understand their psychological state, enable the patient to build confidence and courage to overcome the disease, enable the patient to have an optimistic attitude in a positive atmosphere, and receive treatment with positive emotions.
Optic neuromyelitis safe care
- NMO patients may have functional impairments, such as visual impairment, limb weakness, etc. It is prone to accidents such as bumps, falls and falls. Therefore, the layout of the ward should be safe and reasonable, with sufficient light, flat ground, clean water, and no obstructions. There should be handrails in the bathroom. Protective racks should be placed on both sides of the patient's bed to reduce the height of the bed. No slippers and flat shoes Or non-slip shoes.
Optic neuromyelitis drug care
- Take the medicine regularly according to your doctor's advice. Do not reduce or stop it at will.
Optic neuromyelitis diet care
- Avoid crude fiber and hot and hard foods and irritating foods. Eat low-fat, high-protein, vitamin-rich, potassium-rich, and calcium-rich diets. Foods rich in linoleic acid are also appropriate. Drink plenty of water and eat more meat, vegetables and fruits to increase your protein and vitamin intake.
Optic neuromyelitis prevention infection care
- Prevent patients with paralysis of the lungs from bedridden for a long time, with reduced activity, low resistance, and easy to be complicated by lung infections. Patients must be encouraged and assisted to turn over and pat their backs, 2 h / time. 3 min / time. Slap the left side when lying on the right side and the right side when lying on the left side. It can avoid the accumulation of secretions in the lower respiratory tract, facilitate the discharge of secretions, and prevent the occurrence of epidemic pneumonia. Keep your mouth clean and brush your teeth or oral care at least twice a day. Maintain indoor cleanliness and air circulation, regular air disinfection, room floor and surface of objects. Wipe with 5% peroxyacetic acid.
- Turn around regularly to prevent bed sores, massage the scapular, sacral, heel, ankle and other bone processes at the same time. The pressure-prone areas should be protected with air balloons, cotton rings, sponge pads, and often wash the back and arms with warm water. Talcum powder to keep skin clean. When using a hot water bottle, the water temperature does not exceed 50 , regular massage, promote blood circulation, timely clean or replace the dirty mattresses and clothes, keep the beds flat and clean, make patients comfortable, and prevent pressure ulcers.
- Prevention of urinary tract infections For mild urinary retention, apply a warm towel to the lower abdomen and massage gently, change the position, use the usual squatting or upright position to urinate, listen to the sound of flowing water to induce urination, and guide patients who fail to induce urination Pee.
- Prevention of constipation Due to spinal cord injury, paralysis, bedridden, decreased appetite, weakened bowel movements, and autonomic nervous disorders can easily cause constipation. You should eat more fruits and vegetables and crude fiber foods, develop a regular bowel movement habit, you can l-2 h after eating Massage the abdomen to promote bowel movements. If necessary, give an enema to help defecation. [11]
Optic neuromyelitis rehabilitation care
- Patients should be assisted in taking limb function exercises early, mainly including body positioning and regular turning exercises. Utilize the activities of the trunk muscles, through joint reactions, joint movements, posture reflexes and other means to promote the recovery of the function of the scapular strap to achieve the conversion from the supine position to the bedside position independently, starting from the large joints to the small joints. When the weight is reached, gradually and gradually restore muscle strength, when the muscle strength is still acceptable, encourage patients to actively train standing and walking, start support training and long standing, and gradually train independent walking, which can be supplemented with massage, physical therapy, acupuncture, and accelerate nerve function recovery and improve Functional status of the patient.