What is myasthenia gravis?
Myasthenia gravis or according to ICD-10 simplifies myasthenia gravis belongs to a group of neurological disorders that are characterized by an impaired signal transmission between nerve and muscle and are summarized as disorders of neuromuscular transmission or myasthenic syndromes. It is an autoimmune disease in which a disturbance at the neuromuscular junction of striated muscle (skeletal muscle) is present, the cause is not fully understood.
The symptoms of myasthenia gravis is characterized by a load-dependent muscle weakness, often asymmetrical attacks the muscles mentioned above, also one or more muscles, regardless of the body. To the main symptoms include their changing expression, for example, they may change next to the affected muscles, often during the day spontaneously grow for no apparent reason, and / or it may be a recovery of the affected muscles at rest as suddenly occur again.
Myasthenia gravis occurs both in humans and in animals, especially in domestic dogs before.
Myasthenia gravis in humans
Frequency
Myasthenia gravis is a relatively rare disease. The disease frequency (prevalence) is about 100 to 200 cases per 1 million inhabitants. The disease can manifest at any age, but it has two manifestations summit. The first summit between the second and third decades of life with preference for the female sex, the second summit between the sixth and eighth decade of life, with preference for the male sex. Myasthenia gravis is more common in women (ratio 3: 2). In North America and Europe 10 to 14% of the patients are younger than 10 years. The disease incidence has increased since the beginning of epidemiological surveys in 1950 to this disease; In the 1990s, the disease incidence was approximately four times higher. This increase is attributed to the increasing awareness of the disease, to better diagnostic methods, the decrease in mortality and changes in the age structure of the population.
Cause and pathogenesis
Myasthenia gravis is an autoimmune disease, that is, the body produces autoantibodies against endogenous structures. When myasthenia gravis there are antibodies which are directed against structures of the post-synaptic membrane in the region of the neuromuscular junction. By far the most common, in about 85 percent of cases, acetylcholine receptor antibodies are detectable, ie antibodies directed against the nicotinic acetylcholine receptor. 1 to 10% of patients antibodies against the muscle-specific tyrosine kinase (MuSK) and so-called in some affected low-affinity acetylcholine receptor antibodies or antibodies against lipoprotein receptor-related protein (LRP4) can be detected. In a subset of patients who are suffering with high probability of myasthenia gravis, fails to make antibody detection (seronegative myasthenia gravis)
It is thought that there may be other relevant antibodies Myasthenia addition to the aforementioned antibodies. Shown are merely existing relationships to Myasthenic relevant antibodies and the thymus and the causal basis of the disease, the disturbed signal transmission between nerve and muscle. Another open issue is the cause of the symptoms associated with fluctuating environmental conditions, infections, inflammation, mental and psychological stress.
Acetylcholine receptor antibodies
The interaction between the transmitter acetylcholine and its receptor is prevented or hindered by acetylcholine receptor antibodies. Therefore, the electrical impulse can (the action potential) are not transferred from the nerve to the muscle, the muscle is not energized. In addition, reducing the number of acetylcholine receptors as can be degraded by an immune activity by the binding of antibodies to acetylcholine receptors same. It breaks down the structure of the subsynaptic membrane fragments. By endocytosis results in a autophagosome. Transport vesicles with digestive enzymes merge with the autophagosome. The acetylcholine receptors are degraded by this immune reaction every two to three days. The structure of the neuromuscular junction is changed. The subsynaptic folds (junctional folds) are flat, and the synaptic gap is wider. This has the consequence that the acetylcholine diffuses in its distribution from the synaptic cleft or it is hydrolyzed by the enzyme cholinesterase, before it can occupy an acetylcholine receptor.
Importance of the thymus
In myasthenia gravis very common pathological changes in the thymus are detectable. The thymus is ascribed an important role in the development of the autoimmune process. In up to 70% of cases thymitis (lymphofollikuläre hyperplasia) is striking with active germinal centers. In 10-15% of patients thymoma is detectable. Under certain circumstances, the surgical removal of the thymus affect the disease course positive.
Myasthenia gravis treatment
In the drug treatment of myasthenia gravis 3 different treatment principles can be distinguished. Operationally, can influence the course of the disease may require a removal of the thymus gland.
The therapy with acetylcholinesterase inhibitors used to improve the neuromuscular transmission. They inhibit the enzyme Acetylchoninesterase and thus the breakdown of acetylcholine in the synaptic cleft. Characterized both the temporal availability as well as the concentration of acetylcholine in the synaptic gap is increased. Accordingly, the postsynaptic acetylcholine receptors located stay longer busy and active longer in time. The myasthenic symptoms speaks variably to therapy with acetylcholinesterase inhibitors. While the weakness of the extremities muscles often significantly improved, such as double vision often speak not respond well to therapy.
The active ingredients of Mestinon used for oral administration and the rare bromine intolerance Ambeniumchlorid. Neostigmine and also Pyridostigmine available are available for intravenous use. The treatment with acetyl Cholineste is purely symptomatic treatment, which cannot influence the course of the disease or the prognosis of the disease. Important side effects of the treatment with acetyl Cholineste are excessive sweating and muscle spasms. In high doses, the risk of a cholinergic crisis is so that a dose of 600 mg should be exceeded only in exceptional circumstances.
The immunosuppressive treatment with glucocorticoids or azathioprine can mitigate the effect of the antibody. A plasmapheresis or high-dose immune globulin gifts be used for serious or critical diagram.
There is also the possibility of surgical removal of the thymus or a Thymoms (thym polypectomy). A changeover to less aspiration dangerous diet, swallowing therapy and in severe cases is may be required nutrition by PEG (feeding tube), cutting-edge secretion suction or tracheostomy (tracheotomy). Should remain constant ghosting in ocular myasthenia, an ophthalmologically appropriate Prism in glasses or an ansaugbare by means of water film on a glass of an existing watch glasses or indispensable Prism foil compensates.
History and Cure views
Leaving only the eye muscles affected, the prognosis is good and controlled with medical therapy. The spread on the entire body (generalization) was, however, a few years ago incurable. With modern medicine, the prognosis in recent years has become much better in these cases. But this means a lifelong medication. Other measures such. As mentioned PEG or tracheostomy prolongs life, but can mean a significant loss of quality of life. Due to late or even lack of diagnosis, severe cases and crises (see Complications) can be shorten its life.
Thymectomy often leads especially in young patients to a decrease in symptoms. In this case, the discontinuation of immunosuppressive drugs is several years after the Thymusentfernung may be possible and thus establish a clear improvement, sometimes a remission is achieved.
Myasthenia gravis in animals
Myasthenia gravis is mainly used for domestic dogs (and cats beside or livestock) ago. Here are differentiated congenital and acquired form. The pathogenesis is the same as for humans, so an autoimmune disease, which is directed against the acetylcholine receptors. The treatment is carried out as in humans.
Congenital myasthenia gravis
Congenital Myasthenia gravis is relatively rare and occurs more frequently in some breeds (Jack Russell Terrier, Smooth Fox Terrier hair, Springer Spaniel) on. The disease is inherited as an autosomal recessive trait and typically occurs in 6 to 8 weeks of age.
Acquired myasthenia gravis
Due to likely multicausal, and probably also a genetic predisposition exists and the acquired myasthenia gravis is more common. Thymome also come as a trigger to consider. Age predisposition is two-phasic, with a frequency peak at young dogs (1-4 years of age) and one in old dogs (from 9 years of age).
Clinically it is expressed mostly in local muscle disorders. Often (about 80% of cases) particularly the esophagus is affected, and it develops a mega esophagus. A common Regurgitieren demonstrates clinically. Here is a particularly high risk for an aspiration pneumonia. Also the throat muscles may be involved, what manifests itself in voice changes. The eye muscles are a third common localization as humans. In this case, the eyelid closing reflex is diminished and quickly ermudbar. The generalized form is expressed in quick fatigue, stiff response to going to a Paraparesis of Hindlimbs or quadriplegia. Also a mega esophagus is common. A myasthenic crisis with acute para - and quadriplegia mega esophagus may also occur.
The diagnosis can be ensured only with the detection of antibodies. In a megaesophagus or thymoma an x-ray of the chest can provide important information. Differential diagnosis includes other polyneuropathies, botulism must (rare in dogs), polymyositis, Zeckenparalyse (rarely) and acetylcholine or organophosphate poisoning are excluded (See also VETAMIN D).