Myasthenia gravis (myasthenia gravis pseudoparalitica) is a disease characterized by pathological muscle fatigue.
Pathogenesis
Myasthenia gravis is an autoimmune disease associated with the formation of antibodies to the receptors of the postsynaptic membrane with its subsequent destruction and block of neuromuscular transmission. In 15–30% of cases, myasthenia gravis is accompanied by hyperplasia or a tumor of the thymus gland (thymoma). These patients have cross-reacting antibodies to myoid cells of the thymus gland. There are family cases, but the hereditary transmission of the disease has not been proven.
Myasthenic syndromes may be associated to autoimmune diseases, such as polymyositis and dermatomyositis, as well as to lung, breast, ovarian, and prostate cancers.
The mechanisms of pathogenesis are as follows:
- presynaptic (abnormal synthesis and release of acetylcholine);
- postsynaptic (acetylcholinesterase deficiency, receptor malfunction).
Pathomorphology
There are no disease-specific changes in the CNS, peripheral nerves or muscles in myasthenia gravis. Some patients have enlarged thymus gland or thymoma. Atrophic and dystrophic changes in individual fibers and infiltration of lymphohistiocytic elements of interstitial tissue are detected in striated muscles.
Clinical presentation
Women are affected more common than men. In general, the disease develops at the age of 20–30 years, but it also may occur in children. The main clinical manifestations is the syndrome of pathological muscle fatigue, i.e., fatigue that is not associated with normal physiological fatigue during physical exertion. Muscle weakness increases with movements, aggravates in the evenings.
There are the following forms of myasthenia gravis:
- generalized;
- local (often ocular).
In the latter case, the symptoms are limited to isolated oculomotor disorders. Weakness of the extraocular muscles leads to diplopia and strabismus, unilateral or bilateral ptosis, most pronounced by the end of the day. Weakness of the facial and masticatory muscles is often noted. Difficulties in speech and swallowing can be detected after a long (or not so long) conversation, eating. Clinical presentation may include weakness and increased fatigue of the muscles of the tongue, a nasal twang.
As striated musculature of the extremities, trunk and neck, facial muscles are affected, widespread muscle weakness progresses. In patients with a generalized form of myasthenia gravis, respiratory disorders may occur. Patients may suffer from the weakness of the sphincters, accompanied by urinary and fecal incontinence.
The symptoms are labile, dynamic, increase when reading, fixing the gaze, sometimes with general physical exertion. Examination reveals rapid reduction of tendon reflexes. Sensitive disorders are not typical.
Course
This disease, as a rule, has a progressive nature, although there are variants of a favorable course. Myasthenic episodes (short-lasting myasthenic disorders and prolonged spontaneous remissions, in particular, with an isolated ocular form of myasthenia gravis) and myasthenic states (stable and prolonged manifestations of myasthenia gravis) may occur. Patients with generalized myasthenia gravis may experience a sharp deterioration in the form of a myasthenic crisis with widespread muscle weakness, oculomotor and bulbar symptoms (aphonia, dysarthria, dysphagia), respiratory disorders, as well as autonomic disorders. It may result in acute cerebral hypoxia with an impaired consciousness. A fatal outcome may occur.
Diagnosis and differential diagnosis
Myasthenia gravis is diagnosed on the basis of the clinical presentation (complaints of increased fatigue, with deterioration in the evening, with physical exertion). EMG stimulation demonstrates normal total muscle action potentials at the beginning of the study, with reduction in response to rhythmic stimulation at a rate of 3–5 and 50 pulses per second ("decremental response" of the amplitude). In response to repeated electrical stimulation, pathological muscle fatigue is revealed, with a pronounced ability to recover after a short rest. The neostigmine test is of great importance. It results in a sharp decrease in symptoms in 30-60 minutes after a subcutaneous injection of 1–2 ml of 0.05% neostigmine methylsulfate solution (Proserin♠). The results of the neostigmine test can be confirmed by EMG. If a patient already takes anticholinesterase drugs, therapy should be stopped for EMG to be accurate and valid. If patient’s condition is severe so as therapy cannot be postponed, short-acting drugs (neostigmine methylsulfate) may be considered. To establish a diagnosis, blood test for anti-acetylcholine receptor antibodies is mandatory. CT or MRI of the mediastinum may demonstrate thymoma.
The differential diagnosis includes botulism, brainstem encephalitis, brainstem tumor, basal meningitis, ocular form of myopathy, polymyositis, vertebrobasilar cerebrovascular disease. Oncological process in the internal organs, primarily in the lungs (Lambert-Eaton myasthenic syndrome (LEMS)) should be excluded. It is necessary to exclude myasthenic syndromes associated with certain drugs — aminoglycosides, polymyxin B, penicillamine.
Treatment is aimed at correcting the relative deficiency of acetylcholine and suppressing the autoimmune process. In order to compensate disorders of neuromuscular transmission, anticholinesterase agents are used, such as neostigmine methylsulfate (Proserin♠), ambenonium chloride (Oxazil℘), pyridostigmine bromide (Kalymin♠, Neuromidin♠). It is important to tailor the optimal individually compensating dose depending on the clinical presentation, severity of symptoms, concomitant diseases, drug response. In patients with pharyngofacial and ocular forms of myasthenia gravis, pyridostigmine bromide, neostigmine methylsulfate and ambenonium chloride are more effective. The doses of drugs and the intervals between doses are individual. Moreover, potassium chloride or orotic acid (Potassium orotate♠), spironolactone (Verospiron♠), ephedrine are prescribed.