A 43-year-old woman presents to her general practitioner (GP) complaining of diplopia, more marked in the evenings, for the last 3 months. She has noticed difficulty holding her head up, again especially in the evenings. She has problems finishing a meal because of difficulty chewing. Her husband and friends have noticed that her voice has become quieter. She has lost about 3kg in weight in the past 6 months. The woman has had no significant previous medical illnesses. She lives with her husband and three children. She is a non-smoker and drinks about 15 units of alcohol per week. She is taking no regular medication.
Examination She looks well, and examination of the cardiovascular, respiratory and abdominal systems is normal. Power in all muscle groups is grossly normal but seems to decrease after testing a movement repetitively. Tone, coordination, reflexes and sensation are normal. Bilateral ptosis is present and is exacerbated by prolonged upward gaze. Pupillary reflexes, eye movements and funduscopy are normal.
Questions • What is the diagnosis? • What are the major differential diagnoses? • How would you investigate and manage this patient?
ANSWER
This woman’s generalized weakness is due to myasthenia gravis. Myasthenia gravis is due to the presence of acetylcholine receptor antibodies causing impaired neuromuscular transmission. It characteristically affects the external ocular, bulbar, neck and shoulder girdle muscles. Weakness is worse after repetitive movements which cause acetylcholine depletion from the presynaptic terminals. The onset is usually gradual. Ptosis of the upper lids is often associated with diplopia due to weakness of the external ocular muscles. Speech may become soft when the patient is tired. Symptoms are usually worse in the evenings and better in the mornings. Permanent paralysis eventually develops in some muscle groups. In severe cases respiratory weakness occurs.
• Motor neurone disease: suggested clinically by muscle fasciculation and later by marked muscle weakness. • Muscular dystrophies: selective muscular weakness occurs in specific diseases, e.g. facioscapulohumeral dystrophy. There is usually a family history. • Dystrophia myotonica: this causes ptosis, wasting of the masseter, temporal and sternomastoid muscles and distal muscular atrophy. There is a characteristic facial appearance with frontal baldness, expressionless facies and sunken cheeks. There may be gonadal atrophy and mental retardation. There is usually a family history. The electromyogram (EMG) is diagnostic. • Polymyositis: this may have an acute or chronic onset. A skin rash and joint pains are common. The creatine kinase level is raised and a muscle biopsy is diagnostic. • Miscellaneous myopathies: thyrotoxic, hypothyroid, Cushing’s, alcoholic. • Non-metastatic associations of malignancy: thymoma is associated with myasthenia gravis in 10 per cent of cases; the Eaton–Lambert myasthenic syndrome is associated with small-cell lung carcinoma. Differential diagnoses of generalized muscle weakness
This patient should be investigated by a neurologist. Electromyography (EMG) will demonstrate fatiguability in response to repetitive supramaximal stimulation. Intravenous injection of edrophonium (Tensilon) will increase muscular power for a few minutes. Blood should be assayed for acetylcholine receptor antibodies (present in 90 per cent). A computed tomography (CT) of the thorax should be performed to detect the presence of a thymoma or lung cancer. Corticosteroids are the drugs of first choice. Anticholinesterase drugs greatly improve muscle power but have many side-effects. Thymectomy should be considered. It is most effective within 5 years of diagnosis and when there is no thymoma.