Vignette says a 35 year old woman presents to her primary care physician with chief complaints of progressive muscle weakness over the past few months; She initially noticed difficulty keeping her eyelids open particularly in the evening; She also reports of difficulty swallowing (dysphagia), slurred speech (dysarthria) and double vision (diplopia) particularly in the evening which eventually improves with rest; She also reports weakness in her legs and arms, especially after walking or using her arms for prolonged periods; Examination shows normal deep tendon reflexes with no sensory deficits; Fatigability test is positive; Vital signs are normal; Laboratory studies show positive anti-acetyl choline receptor antibodies and anti-MUSK (muscle specific kinase) antibodies; Edrophonium test shows improvement of motor function for a few minutes; Electromyography shows progressive decline in muscle action potential amplitude with repetitive stimulation; MRI of the chest shows thymoma; Diagnosis?
Diagnosis is Myasthenia gravis.
Myasthenia gravis is an autoimmune disorder of muscle weakness that occurs due to production of auto antibodies against acetylcholine receptors present at the postsynaptic neuromuscular junction; Associated with HLA-DR3; It is commonly present in young woman; Usually associated with thymoma (paraneoplastic syndrome) as 30% of the patients with thymoma develop Anti-acetylcholine receptor antibodies and subsequently myasthenia gravis.
Clinical Features:-
1. The cardinal feature of the MG is the fluctuating weakness with the fatigability (i.e. worsens with repetitive use and relief by rest); Vignette says a young woman with ptosis, diplopia, dysphagia, and dysarthria that worsens particularly in the evening; Exacerbations triggered by stressors such as infections, surgery, pregnancy, and medications (e.g. aminoglycosides and fluoroquinolones).
Diagnosis:-
1. Anti-Acetyl choline receptor antibodies are positive.
2. Anti-MUSK (muscle specific kinase) antibodies are positive.
3. Tensilon test:- Edrophonium is a short acting acetylcholinesterase inhibitor; temporarily increases acetylcholine in NMJ and leads to improvement of motor function for a few minutes.
4. Electromyography shows progressive decline in muscle action potential amplitude with repetitive stimulation.
5. Ice Pack test shows improvement of neuromuscular transmission after application of ice packs in affected muscles for 10 minutes.
Treatment:-
1. Long acting acetylcholinesterase inhibitors (e.g. neostigmine, pyridostigmine).
2. Steroids (e.g. prednisolone).
3. Immunosuppressive drugs (e.g. azathioprine, tacrolimus, cyclophosphamide, or mycophenolate are used in order to get the patient off of steroids).
4. IVIG and/or plasmapheresis (generally used in myasthenic crisis for rapid response).
5. Thymectomy if thymoma is present.
6. Avoid fluoroquinolones and aminoglycosides (exacerbate myasthenia).