ophthalmic myasthenia gravis
Introduction
Ophthalmology myasthenia gravis Myastheniagravis (MG) is a chronic autoimmune disease that involves the acetylcholine receptors in the postsynaptic membrane at the neuro-muscle junction, resulting in neurotransmitter-to-muscle excitation transmission disorders. basic knowledge The proportion of illness: 0.005% Susceptible people: no special people Mode of infection: non-infectious Complications: Diabetes Scleroderma Dermatomyositis
Cause
Ophthalmic myasthenia gravis
(1) Causes of the disease
The etiology of myasthenia gravis is still not completely clear. Comprehensive literatures at home and abroad have been thought to be related to the synthesis of acetylcholine or the disorder of cholinesterase metabolism and the toxicity of certain antibiotics. In recent years, due to the research progress in immunology, it is considered The disease is an autoimmune disease.
(two) pathogenesis
1. Metabolic disorder The disease causing the disease is located in the nerve-muscle junction of the striated muscle. Symptoms are similar to the action of arrow toxins, which hinder the conduction of nerve impulses. The conduction between nerves and muscles is caused by nerve impulses, releasing acetylcholine. The endplate membrane produces a potential difference, which is then transmitted to the muscle to cause the fiber to contract. In patients with myasthenia gravis, when the nerve impulse is transmitted, the acetylcholine is insufficient, or the cholinesterase activity is too high, so that the acetylcholine is destroyed too fast. Causes the onset of neuro-muscle excitation transmission disorders.
2. Toxic effects of drugs Some antibiotics have a blocking effect on neuromuscular conduction in patients with myasthenia gravis. Hokkane reported 6 patients with myasthenia gravis. After treatment with drugs, streptomycin antibiotics were added (15 min). ~2h), the disease is aggravated, such drugs are: streptomycin, dihydrostreptomycin, neomycin, polymyxin, kanamycin, paromomycin, zirconia, etc., Lillmann Etc., suppose that d-tubocurarine (an arrow toxin) has a neuromuscular blockade of 1000, polymyxin B is 5, neomycin is 2.5, streptomycin is 0.7, and dihydrostreptomycin At 0.6, kanamycin is 0.5, and the dose of antibiotics applied clinically is more than 100 times higher than that of arrow toxin. Therefore, the neuromuscular conduction of patients with myasthenia gravis has been blocked, or relying on drugs to maintain balance. Under this circumstance, once the above antibiotics are applied, this blockage will inevitably worsen and the condition will worsen. It is still unclear about the blockade effect of certain antibiotics on nerve-muscle conduction. Some people think that streptomycin and arrow toxin are considered. The same can reduce the endplate acetylation The sensitivity of the base, some people think it can reduce the release of neurotransmitters (transmitter) is.
3. Autoimmune theory In recent years, domestic and foreign scholars believe that myasthenia gravis is an autoimmune myopathy. Simpson and Nastk found anti-acetylcholine receptor (AChR) antibodies in the serum of patients. Therefore, the theory of autoimmune response is proposed, and AChR is considered to be In this case, it can become an autoantigen, stimulate the body to produce antibodies (AChR antibodies), mainly IgG, antigen-antibody binding activates complement, deposits on the motor endplate, causes neuromuscular conduction disorder, and causes muscle weakness symptoms. Patrick and Lindstron confirmed by experimental models. The endplates of the exercise plate have IgG and C3, the immune complex sedimentation and the microstructural changes of the motor endplate, and the AChR of the joint is found to decrease, and the reason for the decrease is:
1AChR antibody has an immunopharmacological blocking effect on the AChR active site;
2AChR turnover changes, promoting the degradation of AChR;
3 Complement-dependent AChR destruction, the reduction of AChR reduces the amount of binding to acetylcholine, and reduces the excitability of neuromuscular or even conduction disorders. Clinical efforts to increase the concentration of local acetylcholine (AChR) will be an effective treatment, and the production of AChR antibodies Mainly lymphocytes, clinical patients also have thymus abnormalities, and can also be combined with other autoimmune diseases, because the thymus is the immune central organ, if the function of the immune central organs is weakened or disappeared, the lymphocytes will be reduced, the antigen When stimulated, little or no AChR antibody is produced, and AChR is not damaged, that is, it can maintain normal neuro-muscle excitability. Therefore, clinical removal of the thymus sometimes has a better therapeutic effect on the disease.
The literature reports that thymus abnormalities in patients with myasthenia gravis are as high as 50% to 70%, of which 10% to 20% are associated with thymoma, about 50% of cases have thymus enlargement, 40% of erythrocyte sedimentation rate increases, 30% to 50% serum Increased globulin, elevated immunoglobulins in tissues (skeletal muscle, myocardium, thyroid, adrenal gland), anti-muscle antibodies, anti-nuclear antibodies, anti-thyroid antibodies, and sometimes anti-gastric antibodies in serum, serum complement The price is low, and it increases specifically with the relief of symptoms, decreases with the aggravation of symptoms, has factors that impede the excitatory transmission of the nerve-muscle junction (body fluid, lymphocytes, etc.), the patient's thymic medullary lymphoid changes and autoimmunity Thyroiditis has similar thyroid changes, so this disease is often complicated by hyperthyroidism, rheumatoid arthritis, lupus erythematosus, bronchial asthma and other autoimmune diseases. High doses of corticosteroids and other immunosuppressants are used to obtain better curative effect. The above facts prove that the disease is related to autoimmunity.
Prevention
Ophthalmology myasthenia gravis prevention
For patients with clear diagnosis, any drug that can affect neuromuscular conduction function should be avoided, such as: aminoglycoside antibiotics - streptomycin, kanamycin and gentamicin, peptide polymyxin, Tetracyclines - chlortetracycline, oxytetracycline, and creatinine-like drugs - quinine, quinidine, procaine, etc., in addition to propranolol, phenytoin and penicillamine.
Complication
Ophthalmologic myasthenia gravis Complications Diabetic scleroderma dermatomyositis
Myasthenia gravis may be associated with hyperthyroidism, Hashimoto's disease, diabetes, etc., and may also have various autoimmune diseases such as nodular arteritis, scleroderma, dermatomyositis, Sjögren syndrome, etc., ocular complications Such as atypical retinal degeneration, etc., is relatively rare.
Symptom
Ophthalmic myasthenia gravis symptoms common symptoms ptosis drooping abnormalities
The first symptoms of myasthenia gravis are mostly in the eye, mainly manifested as ptosis, ptosis, extraocular muscle paralysis, pupillary abnormalities and convergent and dysregulated abnormalities, and a simple type of myopia myasthenia gravis (ocular myasthenia gravis) ), the above-mentioned eye symptoms for a long time, and even the extraocular muscles of both eyes are mostly paralyzed, the eyeballs are completely unable to rotate, but no systemic muscle symptoms appear.
1. The ptosis is a common initial symptom, accounting for 86%. It is better in the morning, and the symptoms become heavier in the afternoon or evening. Generally, the disease starts first. After a period of time, the other eye can also develop the disease. The ptosis is drooping, but to varying degrees, ptosis myasthenia grayis ocularis (PMGO) often exhibits the following characteristics:
(1) The diaphragmatic muscle weakness: When the patient blinks many times, the muscle activity is gradually weakened, the upper jaw is drooping, and the cleft palate is small.
(2) Cogan twitch sign: (Cogan twitch sign: For patients with ptosis, first let them look down, then let them quickly look straight ahead, then the upper jaw will contract upwards, then Restore to the original ptosis position.
(3) Osber eyes (Osber peek sign): The patient closes his eyes. After 1~2 s, the quilting is slightly enlarged and widened to reveal the lower sclera, which is in a blinking state. The cause of muscle fatigue.
(4) Persistent gaze fatigue: When the patient's eyes turn to the right and left, the eyes are more coordinated. If you continue to gaze at the side, the eye will slowly lag behind and tend to return to the first eye position. There are lesions in the nerve junction.
2. Retraction ocularis Myasthenia gravis is not common, mostly temporary, usually occurs after a long period of gaze, and only lasts for a few seconds, due to the presence of upper eyelid retraction, easily lead to misdiagnosis Puklin reported that 3 patients with myasthenia gravis showed upper extremity withdrawal symptoms, and the retraction of the upper jaw was divided into three types according to the withdrawal time:
(1) Temporary eyelid retraction: This type of eyelid retraction occurs mostly after long-term gaze or gaze directly in front of the body. These activities cause long-term contraction of the levator muscle, similar to the mechanical rigidity caused, usually lasting for a few seconds. .
(2) Transient eyelid retraction: It is characterized in that when the eye is turned from the downward gaze position to the first eye position, the upper jaw is lifted above the normal position, because when the downward gaze is taken, the diaphragm is placed in a resting state. Its transient response is more powerful than in other situations, and this momentary eyelid retreat, Cogan once described as "eye twitching", generally lasting less than 1 s.
(3) Long-term upper eyelid retraction: it is the most frequently reported type of myasthenia gravis, and combined with the contralateral upper iliac muscle weakening, Walsh reported 63 cases of myasthenia gravis with single eye or both eyes with ptosis, 2 cases One side of the iliac crest retracted, one case of the upper chin drooping into the upper eyelid retraction, the other case of the upper ptosis combined with the other eyelid retraction, the retracted upper iliac can not fall with the eyeball down, Gay reported 4 cases in There are several clinical phenomena in which the position of the eyelids is asymmetrical under different pathological conditions, 2 of which are myasthenia gravis, but when covering the upper eyelid ptosis, the other symptoms of the eyelid withdrawal are alleviated or returned to normal, and Teng Xilong (tensilon) is injected. The posterior ptosis and withdrawal symptoms disappear at the same time. Therefore, it is considered that the bilateral levator palpebral muscles are the mate muscles, and the Hering's law of innervation is also followed. The muscle weakness of the ptosis on one side should lead to bilateral levator sacral nerve innervation. Strengthened, the result is that the eyelids retreat from the other eye (the upper eye does not hang down).
3. At the same time of eye movement disorder and ptosis, eye movement disorder and diplopia often occur, accounting for 67%, of which more than the above obstacles, followed by internal rectus paralysis, one or both sides, the degree can be From single eye muscle paralysis to total eye muscle paralysis.
4. Pupil movement disorder Using the infrared electronic pupil meter to measure the pupil response to light, the speed of the pupil contraction process is low, and the intravenous injection of Teng Xilong is transient recovery.
5. Convergence and regulation abnormalities In addition to the ocular dyskinesia, convergence and dysregulation may also occur. It is well known that the extraocular muscles of patients with myasthenia gravis are violated, but the intraocular muscle invasion has not been recognized. Manson has 9 cases of severe disease. Myasthenia gravis patients underwent adjustment of near-point measurements. Eight of them were treated with anti-cholinesterase drugs, and the near-point distance was shortened by 8 to 15 cm. Patients with myasthenia gravis had more severe visual impairment and generally did not feel near vision abnormalities. Therefore, it is pointed out that dysregulation is more common in patients with myasthenia gravis. The contractile smooth muscle in the ciliary body is dominated by the rich and refined autonomic nervous system. In the myasthenia gravis patients, this nerve is also violated, not limited to striated muscle disorders.
Examine
Ophthalmologic myasthenia gravis
1. Determination of AChR antibody in blood: AChR can be labeled with 125I--BuTx (125 iodine--bungarotoxin) for radioimmunoassay, and AChR can also be used as antigen to determine AChR antibody. Positive ones are helpful for diagnosis.
2. Urine examination: creatinine excretion is reduced and creatine appears.
3. Peripheral blood routinely normal: Serum immunoglobulin assay may have 2/3 patient IgG increased, a few may have anti-nuclear antibody positive, most patients have anti-AchR antibody positive in serum, C3 complement is increased, peripheral blood lymphocytes stimulate PHA Normally, the Ach receptor protein response is increased, and a few have reported an increase in the number of T-lymphocytes in the cerebrospinal fluid.
4. Pathological anatomy: The muscle changes visible in this disease are: acute necrosis accompanied by inflammatory cell exudation; progressive atrophy, accompanied by lymphocytic infiltration and agglomeration, called "lymphatic leakage"; individual muscle fibers atrophy.
5. Drug test: The neostigminum test and the tensilon test are commonly used clinically to determine whether muscle strength can be restored. In muscle fatigue, subcutaneous or intramuscular injection of neostigmine 0.5~ 1mg (or tensilons, 10mg intravenously), then observe the extraocular muscle strength once every 10min, continuous observation for half an hour, such as within half an hour symptoms (such as ptosis, eye movement disorder) gradually recovered or almost reached normal, can be determined Diagnosis, if there is vomiting or abdominal pain, subcutaneous injection of atropine 0.25 ~ 0.5mg can be eliminated.
6. Fatigue test: After continuous or passive exercise of the affected muscle group, the patient's muscle weakness symptoms are aggravated, such as observing the fatigue symptoms of ptosis, or continuous sputum reflex examination, and the reflection often changes from normal to weak.
7. Inductive electrical continuous stimulation test: When the affected muscle is repeatedly stimulated by the induced current, muscle contraction begins to appear, and then the muscle contraction gradually weakens, and finally stops, showing a so-called muscle weakness reaction.
8. Cold test: According to Borenstein et al., the decrease of ambient temperature can improve the neuromuscular block of myasthenia gravis, increase the release of acetylcholine in the cold, and decrease the activity of acetylcholinesterase. Therefore, cold test can be used to diagnose ocular myasthenia gravis. The method is to observe the degree of ptosis of the upper jaw after placing the popsicle on the drooping eyelid for about 5 minutes.
9. Electromyography (EMG) examination: The typical EMG showed a low amplitude, and the amplitude attenuation phenomenon improved after injection of Teng Xilong. The characteristic change was the motor action potential induced by motor nerves, and the amplitude was quickly reduced. On the single fiber EMG. It can be seen that the transmission of excitement is delayed or blocked.
Diagnosis
Diagnosis and differentiation of ophthalmologic myasthenia gravis
diagnosis
A preliminary diagnosis can be made based on medical history and clinical manifestations. Drug tests, electromyography and immunological tests can help to confirm the diagnosis.
Differential diagnosis
Myasthenia gravis, myasthenia gravis should be differentiated from Eaton-Lambert syndrome, myopathy caused by thyroid dysfunction, pseudoocular muscle paralysis, progressive extraocular muscle paralysis, and cholinergic crisis.
1.Eaton-Lambert syndrome: also known as myasthenia gravis or muscle weakness syndrome with bronchial lung cancer, is another chronic neuromuscular junction dysfunction, clinical manifestations of fatigue, abnormal sensitivity to arrow poison, Ineffective for cholinesterase inhibitors, EMG performance is different from myasthenia gravis, the disease usually begins after the age of 50, often accompanied by oat cell type bronchogenic lung cancer, muscle weakness symptoms may appear earlier than lung cancer, also seen in Other tumors or no special accompanying disease, muscle weakness mainly manifested in limb distal and trunk muscle weakness, extraocular muscles and medullary inner muscles are less affected, neostigmine has no significant effect on the disease.
2. Thyroid dysfunction extraocular myopathy: Symptoms of thyroid dysfunction, accompanied by diplopia, prominent eyeballs, cleft palate, restricted movement of the eyeball in all directions, and symptoms such as ptosis, thyroid function Check can be identified.
3. False ophthalmoplegia: Also known as Roth-Bielschowsky syndrome, it is caused by all the excitability and inhibition signals transmitted from the brain due to large brain damage, resulting in bilateral total ophthalmoplegia. Command or your own will to do random eye movements, sometimes combined with dyslexia, generally still keep the line of sight parallel, no double vision.
4. Proglessive extemal myopathy: This disease was previously thought to be caused by degenerative lesions of the oculomotor nucleus. Recently, the electromyography and pathological examination proved that the nerve branch distribution wave is completely normal, and the eye muscle itself is normal. There is obvious degeneration, resulting in weakening or disappearing muscle contraction, and changes in muscle nutrition, and muscle atrophy or hypertrophy, the disease is hereditary, mostly occurs before the age of 30, began to sag for both eyes, followed by The movement of the two eyeballs is limited, and finally develops to be completely unable to rotate. The front is mostly kept in a positive position or a slight exotropia. The intraocular muscles are not tired, and the facial muscles and the orbicularis oculi muscle can also be invaded. The neostigmine test does not respond. EMG examination has a strong discharge phenomenon proportional to eye movement disorder.
5. Cholinergic crisis: When applied to excessive cholinesterase inhibitors, intravenous injection of 2-10 mg Teng Xilong has a significant improvement on the muscle weakness crisis, but has no effect on the cholinergic crisis or worsened. .
