MYASTHENIA GRAVIS

MYASTHENIA GRAVIS

A 35-year-old woman comes to the clinic complaining of double vision that seems to worsen near the end of the day. She also complains of difficulty chewing meat and other hard foods. She notices that her symptoms improve following a good night’s sleep. On neurologic examination, you note a snarling appearance when the patient is asked to smile, and a nasal tone is heard in her voice. You also note a weakness in the upper extremities when the patient is asked to clench her fist around your finger repeatedly.

Definition. Myasthenia gravis (MG) is a disease of the neuromuscular junction characterized by weakness and fatigability.

Etiology. In myasthenia gravis, an autoimmune process characterized by acetylcholine-recep- tor antibodies leads to a decreased number of active and functional acetylcholine receptors  at the postsynaptic  membrane.

Clinical Presentation. The major features in a patient’s history that help to diagnose myasthe- nia gravis are muscle weakness and fatigability. Initially, patients will complain of diplopia, ptosis, and difficulty swallowing. Speech may have a “mushy” or nasal quality and facial weak- ness may manifest as a“snarling” appearance when smiling. As the disease progresses, weakness may become generalized, involving proximal muscles in an asymmetric pattern. Deep tendon reflexes are intact. Pupillary responses are normal. There are no sensory abnormalities. Very severe disease may affect the muscles of respiration.

Eaton-Lambert myasthenic syndrome is characterized by increasing muscle strength on repetitive contraction. This syndrome is seen in association with malignancy, especially small-cell carcinoma of the lung.

Botulism may cause a myasthenic-like illness, but the pupils are usually dilated and repetitive nerve stimulation (on EMG) shows an incremental increase in muscular fiber contraction (opposite of myasthenia gravis).

Diagnosis. The best initial test for the diagnosis of myasthenia gravis is the acetylcholine-recep- tor antibody test. In generalized myasthenia gravis, 80–90% of patients will have a positive test. In the presence of fatigable muscle weakness, a positive antibody test is specific and virtually diagnostic. Antibodies are present in only 70% of those with disease limited to the eyes.

The edrophonium (Tensilon) test is sensitive but not specific for the diagnosis. Additionally, patients may experience nausea, diarrhea, fasciculations, syncope (rare), or bradycardia dur- ing the test, which are cholinergic symptoms.

Imaging studies of the chest such as x-rays and CT scan should be performed to detect a thymoma. Thymoma is found in 10–15% of patients. Thymic hyperplasia is found in 65%.

The most accurate test for the diagnosis of myasthenia gravis is electromyography (EMG). The characteristic finding is a decremental decrease in muscle fiber contraction on repetitive nerve stimulation.

Treatment. Anticholinesterase (usually pyridostigmine or neostigmine) medications are useful for the symptomatic treatment of myasthenia gravis. Pyridostigmine is longer lasting. If treatment with anticholinesterase medications is unsuccessful in providing symptomatic relief, the physician should consider immunosuppressive therapy.

There are numerous medications used for immunosuppressive therapy. These interventions primarily differ in the onset of therapeutic benefit. They are used if thymectomy is not effective.

Glucocorticoids are effective in improving weakness but take 1 to 3 months for you to observe a clinical benefit. Steroids are the initial immunosuppressive of choice. If patients fail steroid therapy, azathioprine is the most widely used medication used in combination with steroids. The benefits of azathioprine therapy may take more than 3 to 6 months to peak. Cyclosporine and cyclophosphamide are alternatives to azothiaprine but are more  toxic.

Plasmapheresis and intravenous immunoglobulin are immunosuppressive therapies noted for their ability to rapidly improve weakness in myasthenia gravis. They are therefore reserved for patients in acute myasthenic crisis. These therapies are used when respiratory involvement occurs or when patients go to the operating room.

Thymectomy is indicated in postpubertal patients and in those younger than 60 years of   age with generalized myasthenia gravis before initiation of immunosuppressive therapy.  Thymectomy is performed in those not controlled with anticholinesterase medications to prevent the use of potentially toxic medication such as systemic steroids. Thymectomies are also performed when a thymoma is present to prevent the spread of malignant thymic disease.

Aminoglycoside antibiotics may exacerbate myasthenia gravis and should be avoided. In fact, many medications may worse myasthenia gravis.

Mycophenolate is a newer immunosuppressive drug with less adverse effects than steroids or cyclophosphamide.