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 weakness that does not fluctuate, rather than fatigable weakness. That does not match drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies.
2. Guillain-Barre syndrome Weakness spreading upward with absent reflexes, after an infection. Here, drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies points elsewhere.
3. Motor neurone disease A mix of upper and lower motor neurone signs (a mix of stiffness and wasting). But drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies does not point to it.
4. Myasthenia gravis correct Correct. A drooping eyelid that tires through the day, with chewing weakness and positive acetylcholine receptor antibodies, is myasthenia gravis.
5. Lambert-Eaton myasthenic syndrome Weakness that improves with use, linked to small cell lung cancer. It does not fit drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies.

The point: Myasthenia gravis is an autoimmune disease (the body's immune system attacking its own tissue) of the neuromuscular junction, the point where a nerve signal passes to a muscle. It is caused by antibodies against the acetylcholine receptor, the docking point on the muscle for the nerve signal, or, in a seronegative subset (patients who test negative for that antibody), against muscle-specific kinase, a different muscle protein. The hallmark is fatigable weakness, weakness that gets worse with use and as the day goes on. It shows as ptosis (a drooping eyelid), diplopia (double vision), bulbar symptoms (trouble chewing, swallowing and speaking) and weakness in the limbs closest to the trunk (proximal limb weakness). Reflexes and sensation stay normal, which is a key clue. It is confirmed by a blood test for acetylcholine receptor antibodies, with neurophysiology tests, repetitive nerve stimulation or single-fibre EMG (tests of how well nerve signals reach the muscle), where the antibody test is negative. A CT scan of the thymus gland is done because a thymoma (a thymus tumour) or thymic hyperplasia (an enlarged thymus) is common, and removing the thymus (thymectomy) can help. Treatment is a cholinesterase inhibitor, usually pyridostigmine, for symptom control, plus immunosuppression (corticosteroids and steroid-sparing drugs that calm the immune system) to treat the disease itself. A myasthenic crisis is severe weakness causing respiratory failure. It is monitored by the forced vital capacity (a breathing test that measures lung capacity) and treated with intravenous immunoglobulin or plasma exchange (treatments that remove or dilute the harmful antibodies) alongside breathing support. Many drugs make myasthenia worse, notably aminoglycoside antibiotics and beta-blockers, and steroids can briefly make it worse when first started. Contrast this with Lambert-Eaton myasthenic syndrome, a different condition 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. Pyridostigmine for symptom control correct Correct. Pyridostigmine, a cholinesterase inhibitor, controls the symptoms.
2. Corticosteroids and steroid-sparing immunosuppression Steroids and other drugs that calm the immune system, to control the disease itself. That does not match drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies.
3. Avoid drugs that worsen myasthenia Such as aminoglycoside antibiotics and beta-blockers. Here, drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies points elsewhere.
4. Monitor and support ventilation in a crisis Watching the breathing test and supporting breathing if it worsens. It does not fit drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies.
5. Intravenous immunoglobulin or plasma exchange for a crisis Treatments that remove or dilute the harmful antibodies, for severe weakness or breathing failure. But drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies does not point to it.

The point: Myasthenia gravis is an autoimmune disease (the body's immune system attacking its own tissue) of the neuromuscular junction, the point where a nerve signal passes to a muscle. It is caused by antibodies against the acetylcholine receptor, the docking point on the muscle for the nerve signal, or, in a seronegative subset (patients who test negative for that antibody), against muscle-specific kinase, a different muscle protein. The hallmark is fatigable weakness, weakness that gets worse with use and as the day goes on. It shows as ptosis (a drooping eyelid), diplopia (double vision), bulbar symptoms (trouble chewing, swallowing and speaking) and weakness in the limbs closest to the trunk (proximal limb weakness). Reflexes and sensation stay normal, which is a key clue. It is confirmed by a blood test for acetylcholine receptor antibodies, with neurophysiology tests, repetitive nerve stimulation or single-fibre EMG (tests of how well nerve signals reach the muscle), where the antibody test is negative. A CT scan of the thymus gland is done because a thymoma (a thymus tumour) or thymic hyperplasia (an enlarged thymus) is common, and removing the thymus (thymectomy) can help. Treatment is a cholinesterase inhibitor, usually pyridostigmine, for symptom control, plus immunosuppression (corticosteroids and steroid-sparing drugs that calm the immune system) to treat the disease itself. A myasthenic crisis is severe weakness causing respiratory failure. It is monitored by the forced vital capacity (a breathing test that measures lung capacity) and treated with intravenous immunoglobulin or plasma exchange (treatments that remove or dilute the harmful antibodies) alongside breathing support. Many drugs make myasthenia worse, notably aminoglycoside antibiotics and beta-blockers, and steroids can briefly make it worse when first started. Contrast this with Lambert-Eaton myasthenic syndrome, a different condition 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 definitive treatment?

1. Thymectomy where a thymoma is present or in selected patients correct Correct. The thymus is imaged for a tumour, and removing it can improve the disease.
2. Avoid drugs that worsen myasthenia Such as aminoglycoside antibiotics and beta-blockers. It does not fit drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies.
3. Corticosteroids and steroid-sparing immunosuppression Steroids and other drugs that calm the immune system, to control the disease itself. That does not match drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies.
4. Monitor and support ventilation in a crisis Watching the breathing test and supporting breathing if it worsens. But drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies does not point to it.
5. Intravenous immunoglobulin or plasma exchange for a crisis Treatments that remove or dilute the harmful antibodies, for severe weakness or breathing failure. Here, drooping eyelids and chewing weakness worse in the evening with positive acetylcholine receptor antibodies points elsewhere.

The point: Myasthenia gravis is an autoimmune disease (the body's immune system attacking its own tissue) of the neuromuscular junction, the point where a nerve signal passes to a muscle. It is caused by antibodies against the acetylcholine receptor, the docking point on the muscle for the nerve signal, or, in a seronegative subset (patients who test negative for that antibody), against muscle-specific kinase, a different muscle protein. The hallmark is fatigable weakness, weakness that gets worse with use and as the day goes on. It shows as ptosis (a drooping eyelid), diplopia (double vision), bulbar symptoms (trouble chewing, swallowing and speaking) and weakness in the limbs closest to the trunk (proximal limb weakness). Reflexes and sensation stay normal, which is a key clue. It is confirmed by a blood test for acetylcholine receptor antibodies, with neurophysiology tests, repetitive nerve stimulation or single-fibre EMG (tests of how well nerve signals reach the muscle), where the antibody test is negative. A CT scan of the thymus gland is done because a thymoma (a thymus tumour) or thymic hyperplasia (an enlarged thymus) is common, and removing the thymus (thymectomy) can help. Treatment is a cholinesterase inhibitor, usually pyridostigmine, for symptom control, plus immunosuppression (corticosteroids and steroid-sparing drugs that calm the immune system) to treat the disease itself. A myasthenic crisis is severe weakness causing respiratory failure. It is monitored by the forced vital capacity (a breathing test that measures lung capacity) and treated with intravenous immunoglobulin or plasma exchange (treatments that remove or dilute the harmful antibodies) alongside breathing support. Many drugs make myasthenia worse, notably aminoglycoside antibiotics and beta-blockers, and steroids can briefly make it worse when first started. Contrast this with Lambert-Eaton myasthenic syndrome, a different condition 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