Neurology for MRCP Part 1

A 34-year-old woman has 3 months of drooping eyelids and double vision that are worse in the evening, with difficulty chewing towards the end of a meal. Examination shows fatigable ptosis, and reflexes and sensation are normal. Acetylcholine receptor antibodies are positive. What is the most likely diagnosis?

1. Mitochondrial or muscular myopathy A fixed rather than fatigable weakness. Fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies makes it a consideration.
2. Guillain-Barre syndrome Ascending areflexic weakness after infection. Fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies points elsewhere.
3. Motor neurone disease Mixed upper and lower motor neurone signs. Fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies raises it.
4. Myasthenia gravis correct Correct. Fatigable ptosis and bulbar weakness with positive acetylcholine receptor antibodies is myasthenia gravis.
5. Lambert-Eaton myasthenic syndrome Weakness that improves with use, linked to small cell cancer. Fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies separates it.

The point: Myasthenia gravis is an autoimmune disease of the neuromuscular junction, caused by antibodies to the acetylcholine receptor (or to muscle-specific kinase in a seronegative subset). The hallmark is fatigable weakness that worsens with use and through the day, with ptosis, diplopia, bulbar symptoms (chewing, swallowing and speech) and proximal limb weakness; reflexes and sensation are normal. It is confirmed by acetylcholine receptor antibodies, with neurophysiology (repetitive stimulation or single-fibre EMG) where the antibodies are negative, and a CT of the thymus is done because a thymoma or thymic hyperplasia is common and thymectomy can help. Treatment is a cholinesterase inhibitor (pyridostigmine) for symptoms plus immunosuppression (corticosteroids and steroid-sparing agents). A myasthenic crisis is severe weakness with respiratory failure, monitored by the forced vital capacity and treated with intravenous immunoglobulin or plasma exchange and ventilatory support. Many drugs worsen myasthenia, notably aminoglycosides and beta-blockers, and steroids can transiently worsen it when first started. Contrast Lambert-Eaton myasthenic syndrome, where weakness improves with use and is linked to small cell lung cancer.

Source: Association of British Neurologists — myasthenia gravis guidance Association of British Neurologists · tier 2, specialty society or college

A 34-year-old woman has 3 months of drooping eyelids and double vision that are worse in the evening, with difficulty chewing towards the end of a meal. Examination shows fatigable ptosis, and reflexes and sensation are normal. Acetylcholine receptor antibodies are positive. What is the most appropriate investigation?

1. Acetylcholine receptor antibodies correct Correct. These antibodies confirm the diagnosis in most patients with myasthenia gravis.
2. Forced vital capacity Monitors respiratory involvement. Fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies makes it a safety measure.
3. CT of the thymus Detects a thymoma or hyperplasia. Fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies makes it important.
4. Muscle-specific kinase antibodies where seronegative Identify the seronegative subset. Fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies makes them selective.
5. Repetitive nerve stimulation or single-fibre EMG Neurophysiological confirmation. Fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies makes it supportive.

The point: Myasthenia gravis is an autoimmune disease of the neuromuscular junction, caused by antibodies to the acetylcholine receptor (or to muscle-specific kinase in a seronegative subset). The hallmark is fatigable weakness that worsens with use and through the day, with ptosis, diplopia, bulbar symptoms (chewing, swallowing and speech) and proximal limb weakness; reflexes and sensation are normal. It is confirmed by acetylcholine receptor antibodies, with neurophysiology (repetitive stimulation or single-fibre EMG) where the antibodies are negative, and a CT of the thymus is done because a thymoma or thymic hyperplasia is common and thymectomy can help. Treatment is a cholinesterase inhibitor (pyridostigmine) for symptoms plus immunosuppression (corticosteroids and steroid-sparing agents). A myasthenic crisis is severe weakness with respiratory failure, monitored by the forced vital capacity and treated with intravenous immunoglobulin or plasma exchange and ventilatory support. Many drugs worsen myasthenia, notably aminoglycosides and beta-blockers, and steroids can transiently worsen it when first started. Contrast Lambert-Eaton myasthenic syndrome, where weakness improves with use and is linked to small cell lung cancer.

Source: Association of British Neurologists — myasthenia gravis guidance Association of British Neurologists · tier 2, specialty society or college

A 34-year-old woman has 3 months of drooping eyelids and double vision that are worse in the evening, with difficulty chewing towards the end of a meal. Examination shows fatigable ptosis, and reflexes and sensation are normal. Acetylcholine receptor antibodies are positive. What is the most appropriate management?

1. Thymectomy where a thymoma is present or in selected patients A thymoma is imaged for, and thymectomy can improve the disease, and fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies here points elsewhere.
2. Corticosteroids and steroid-sparing immunosuppression Modify the disease. Fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies makes it foundational.
3. Avoid drugs that worsen myasthenia Such as aminoglycosides and beta-blockers. Fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies makes it a caution.
4. Pyridostigmine for symptom control correct Correct. Pyridostigmine, a cholinesterase inhibitor, controls the symptoms.
5. Monitor and support ventilation in a crisis Guided by the vital capacity. Fatigable ptosis and bulbar weakness worse in the evening with positive acetylcholine receptor antibodies makes it a safety step.

The point: Myasthenia gravis is an autoimmune disease of the neuromuscular junction, caused by antibodies to the acetylcholine receptor (or to muscle-specific kinase in a seronegative subset). The hallmark is fatigable weakness that worsens with use and through the day, with ptosis, diplopia, bulbar symptoms (chewing, swallowing and speech) and proximal limb weakness; reflexes and sensation are normal. It is confirmed by acetylcholine receptor antibodies, with neurophysiology (repetitive stimulation or single-fibre EMG) where the antibodies are negative, and a CT of the thymus is done because a thymoma or thymic hyperplasia is common and thymectomy can help. Treatment is a cholinesterase inhibitor (pyridostigmine) for symptoms plus immunosuppression (corticosteroids and steroid-sparing agents). A myasthenic crisis is severe weakness with respiratory failure, monitored by the forced vital capacity and treated with intravenous immunoglobulin or plasma exchange and ventilatory support. Many drugs worsen myasthenia, notably aminoglycosides and beta-blockers, and steroids can transiently worsen it when first started. Contrast Lambert-Eaton myasthenic syndrome, where weakness improves with use and is linked to small cell lung cancer.

Source: Association of British Neurologists — myasthenia gravis guidance Association of British Neurologists · tier 2, specialty society or college