Myasthenia gravis includes an episodic muscle weakness and easy fatigue caused by autoantibody and cell-mediated destruction of acetylcholine receptors. It occurs in young women are more common, but can occur in men and women at any age. The symptoms worsened by muscle activity and take rest from. The diagnosis is made by determining serum levels of acetylcholine receptor (AChR) antibody, electromyography and through which the weakness is briefly reduced sometimes an i.v. Edrophoniumtest. The treatment consists of the administration of cholinesterase inhibitors, immunosuppressants, corticosteroids, plasma exchange, iv immunoglobulin and possibly thymectomy.
(See also summary of disorders of the peripheral nervous system.)
Myasthenia gravis includes an episodic muscle weakness and easy fatigue caused by autoantibody and cell-mediated destruction of acetylcholine receptors. It occurs in young women are more common, but can occur in men and women at any age. The symptoms worsened by muscle activity and take rest from. The diagnosis is made by determining serum levels of acetylcholine receptor (AChR) antibody, electromyography and through which the weakness is briefly reduced sometimes an i.v. Edrophoniumtest. The treatment consists of the administration of cholinesterase inhibitors, immunosuppressants, corticosteroids, plasma exchange, iv immunoglobulin and possibly thymectomy. (See also overview of disorders of the peripheral nervous system.) Myasthenia gravis is most often made in women aged 20-40 years. Myasthenia gravis is due to an autoimmune attack on postsynaptic acetylcholine receptors, which interrupts the neuromuscular transmission. The trigger for the autoantibody production is unknown, however, the interference with abnormalities of the thymus, autoimmune hyperthyroidism and other autoimmune diseases (eg., Rheumatoid arthritis, SLE, pernicious anemia) is associated. The role of the thymus in myasthenia is unclear, but 65% of patients have a hyperplasia of the thymus and 10% a thymoma. About half of thymomas are malignant. Triggering factors for myasthenia gravis include infection Surgical procedures Certain medications (eg. As aminoglycosides, quinine, magnesium sulfate, procainamide, calcium channel blockers). Abnormal eAntikörper Only about 10-20% of patients with generalized myasthenia have no antibodies to acetylcholine receptors (AChR) in serum; up to 50% of these AChR antibody-negative patients have antibodies against the muscle-specific receptor tyrosine kinase (MuSK), an enzyme of the surface membrane that supports the aggregation of AChR molecules during development of the neuromuscular junction. However, anti-MuSK antibodies do not occur in most patients with AChR antibodies or with isolated ocular myasthenia. The clinical significance of anti-MuSK antibody is still being researched; Patients with these antibodies, however, have a much lower probability of a thymic hyperplasia or thymoma, they may be less responsive to cholinesterase inhibitor and a more aggressive early immunotherapy need as patients with AChR antibodies. Ungewöhliche forms Ocular Myasthenia gravis affects only the extraocular muscles. It accounts for around 15% of cases. Congenital Myasthenia is a rare autosomal recessive disorder with onset in childhood. It is not immune mediated and results from presynaptic or postsynaptic abnormalities, including the following: reduced acetylcholine resynthesis due to a choline deficiency Acetylcholinesterasemangel the end plate Structural changes in the postsynaptic receptor A Ophthalmoplegia is common. A Neugeborenenmyastheniebetrifft 12% of children born to women with myasthenia gravis. It is caused by IgG antibodies passively transferred through the placenta. It causes generalized muscle weakness, which regresses over days to weeks, the antibody titers fall. Therefore, only supportive treatment in general. Symptoms and signs The most common symptoms are ptosis, diplopia and muscle weakness after use of the affected muscle. The weakness disappears when the affected muscles have recovered, but returns when they are loaded again. The eye muscles are affected initially at 40% and finally 85% of patients in 15% of cases they are the only muscles that are affected. If the development of generalized myasthenia after the ocular symptoms, it is usually within 3 years. The handshake between weak and can normally alternate (milkmaids handle). The neck muscles may be weak. A proximal limb weakness is common. Some patients have bulbar symptoms (eg. As altered voice, nasal regurgitation, cough, dysphagia). Sensors and the tendon reflexes are normal. The severity of symptoms fluctuates throughout the day to hours. The myasthenic crisis refers to a severe, generalized quadriplegia or life-threatening respiratory muscle weakness that occurs in 15-20% of patients at least once in a lifetime. It is often caused by adventitious infection that reactivates the immune system. When a respiratory failure sets in, may develop respiratory failure very quickly. The cholinergic crisis is a muscle weakness, may be the result of too high doses of cholinesterase inhibitors (eg. As neostigmine, pyridostigmine). Distinguishing a slight crisis of a worsening myasthenia can be difficult. A severe cholinergic crisis can be distinguished as a rule, because they, unlike myasthenia gravis, to increased lacrimation and salivation, tachycardia and diarrhea results. Diagnostic tests at the bedside AChR antibody levels, electromyography, or both, the diagnosis of myasthenia gravis is believed on the basis of symptoms and confirmed by investigations. Examination at the bedside, the traditional anti-cholinesterase test (n. D. Talk .: Tensilon test), which is performed at the bedside and the short-acting (<5 min) using drug edrophonium, is positive in most patients with myasthenia and clear weakness , However, this test should be performed only in patients with obvious ptosis or Ophthalmoparese; these deficits must be present for the recovery indicate clearly to normal strength and thus clear objective evidence come to a positive test result. In the test, patients are asked to burden the affected muscle until this tired (eg to keep his eyes open until ptosis sets in.); then 2 mg edrophonium i.v. given. If no adverse reaction occurs within 30 s (z. B. bradycardia, atrioventricular block) are given a further 8 mg. A rapid (<2 min) improving muscle function is a positive result. However, this test for the following reasons is not ideal: A positive result should not be regarded as a clear confirmation of diagnosis of myasthenia gravis, because these improvements can also occur with other neuromuscular disorders. The results can be questionable, especially if the test is performed in patients without obvious ptosis or Ophthalmoparese. During the test, the weakness may worsen due to a cholinergic crisis; Thus, resuscitation equipment and atropine must be available (as an antidote) during the test. Because weakness subsides at cooler temperatures because of myasthenia, can be used in patients with ptosis of Eisbeuteltest. In this test, an ice pack for 2 min is placed on the closed eyes of the patient and then removed. As a positive result of the complete or partial reduction in ptosis is considered. The Eisbeuteltest not function normally in patients with Ophthalmoparese. Patients with Opthalmoparese be examined with the rest test. In this test, the patient will be asked to lie in a dark room for 5 minutes with your eyes closed quiet. Disappears Ophthalmoparese after this rest period, the result is positive. Tips and risks Try before anticholinesterase test the Eisbeutel- or Hibernation test. Run the anticholinesterase test only in patients with obvious ptosis or Ophthalmoparese through (to get clear results). Antibody tests and electromyography Even if a test at the bedside clear positive outcome is to confirm the diagnosis, one or both of the following studies required: Serum AChR antibody levels electromyography (EMG) AChR antibodies are at 80-90% of patients with generalized myasthenia before, but only in 50% of patients with ocular myasthenia. The antibody levels in the serum did not correlate with the severity of the disease. Up to 50% of patients without AChR antibody test positive for anti-MuSK antibodies. An EMG using repetitive electrical stimulation (2-3 / s) shows a decrement> 10% in the amplitude of the sum muscular action potential at 60% of patients. Single fiber EMG can in> 95% of cases, an abnormal neuromuscular transmission erfassen.Weitere tests If a myasthenia is diagnosed, should be done to exclude or evidence of thymic hyperplasia and a thymoma, a CT scan or MRI of the thorax. Further studies should be carried out as a screening for autoimmune diseases that are often associated with myasthenia (z. B. pernicious anemia, autoimmune hyperthyroidism, rheumatoid arthritis, SLE). Patients in myasthenic crisis should be reviewed on an infectious trigger. Pulmonary lung function tests at the bedside (z. B. forced vital capacity) help to recognize an impending respiratory failure due time. Treatment cholinesterase inhibitors in relieving symptoms corticosteroids, immunomodulatory treatments (eg. B. iv immunoglobulins, plasma exchange), immunosuppressants and thymectomy to reduce the autoimmune response Adjunctive therapy in patients with congenital myasthenia are Cholinesterase inhibitors and immunomodulatory treatments of no use and should be avoided. Patients with respiratory failure require intubation and mechanical ventilation. Symptomatic treatment cholinesterase inhibitors are the mainstay of symptomatic treatment, but do not alter the disease process underlying. Moreover, mend hardly any symptoms and myasthenia can be refractory to these drugs. Pyridostigmine is 60 mg p.o. started every 3-4 h and titrated up to a maximum of 120 mg / dose, depending on the symptoms. If parenteral therapy is necessary (for. Example, because of a dysphagia), neostigmine can (1 mg = 60 mg pyridostigmine) are substituted. Cholinesterase inhibitors can cause abdominal cramps and diarrhea with oral atropine 0.4-0.6 mg (transfer together with pyridostigmine or Neostigmine) are treated daily with or propantheline 3 to 4 times. Patients who had already responded well to treatment and then deteriorate, need because of a possible cholinergic crisis respiratory support, and cholinesterase inhibitors must be discontinued for several days werden.Immunmodulierende treatment immunosuppressants interrupt the autoimmune response and slow disease progression, but they do not achieve fast symptom relief. kg once daily for 5 days after iv administration of IVIG 400 mg / show 70% of patients after 1-2 weeks of improvement. The effects can last 1-2 months. Plasma exchange (eg., 5 exchanges of 3-5 l plasma for 7-14 days) may have similar effects. Many patients require corticosteroids as maintenance therapy, but these have little immediate effect on a myasthenic crisis. About half of the patients deteriorated acutely after initiation of high-dose therapy with corticosteroids. Initial prednisone is administered p.o. 10 mg once daily given; the dose is increased by 10 mg weekly to 60 mg and, about 2 months, then tapered off slowly. Clinical improvement may take several months; then the dose should be reduced to what is necessary to control the symptoms minimum. Azathioprine 2.5-3.5 mg / kg p.o. once a day may be about as effective as corticosteroids if a significant benefit often occurs only after months. Ciclosporin 2-2.5 g / kg p.o. may allow a reduction of the corticosteroid. These drugs require the usual precautions. Other drugs that may be useful are methotrexate, cyclophosphamide, and mycophenolate mofetil. In patients with refractory disease monoclonal antibodies (eculizumab z. B. rituximab) may be advantageous, but are expensive. A thymectomy may be indicated in patients with generalized myasthenia <80 years; it should be performed in all patients with a thymoma. As a result, 80% achieve remission, or maintenance dose can be reduced. Plasma exchange or IVIG are useful in myasthenic crisis and in all patients before thymectomy, do not respond to drugs. Conclusion Consider myasthenia gravis in patients with ptosis, diplopia and muscle weakness after use of the affected muscle. Determine to confirm the diagnosis, the AChR antibody serum levels (which usually vokommen in myasthenia gravis) and perform an electromyography (EMG), or both through. Test after the diagnosis is confirmed on thymus, thymomas, hyperthyroidism and autoimmune diseases that often accompany a myasthenia gravis. Use in most patients cholinesterase inhibitor to relieve the symptoms, and immunomodulatory treatment to slow the disease process and to support the resolution of symptoms; not apply these treatments in patients with congenital myasthenia. When patients who had responded well to treatment, show a sudden deterioration, make breathing assistance ready and set the cholinesterase inhibitors for several days from.