Myasthenia gravis Flashcards
what is the definition of MG?
Myasthenia gravis (MG) is a chronic autoimmune disorder of the postsynaptic membrane at the neuromuscular junction in skeletal muscle. Circulating antibodies against the nicotinic acetylcholine receptor (AChR) or associated proteins impair neuromuscular transmission Antibodies targeted against AChR - in 85% of generalised cases, 50% of ocular MG Anti MuSk = 5-8% Loss of around 60% of AChR needed for symptoms
what is the epidemiology of MG?
More common in women
Women present earlier
Increasing in developed countries
what is the aetiology of MG?
About 80% to 90% of MG patients have detectable antibodies against the nicotinic acetylcholine receptor (AChR) on the postsynaptic muscle membrane at the NMJ. Some patients who do not have detectable AChR antibodies by standard binding and modulating assays have been shown to have AChR binding antibodies using a cell-based assay. Removal of antibodies by plasma exchange or immunosuppression ameliorates symptoms in patients with MG
what are the risk factors for MG?
Family history of autoimmune disease
Genetic markers
cancer -targeted therapy
what is the pathophysiology of MG?
In MG characterised by acetylcholine receptor (AChR) antibodies, an autoimmune attack against AChRs results in destruction of the postsynaptic membrane. The reduced number of available binding sites for acetylcholine leads to inconsistent generation of muscle fibre action potentials, which manifests as skeletal muscle weakness.
Muscle-specific tyrosine kinase (MuSK) is an agrin-dependent protein localised to muscle membranes with an essential role in anchoring AChR at the tips of the postsynaptic folds. Antibodies to MuSK in plasma isolated from patients with MuSK MG strongly inhibited AChR clustering in cultured muscle cells.
Thymus can become associated - immune cell lymphoid hyperplasia, malignancy can occur, 15% of MG have thymoma, 50% of thymoma patient have MG
MG crisis - respiratory failure, imparied swallow, severe limb weakness (more common in anti MuSK patients)
what are the key presentations of MG?
Extraocular-weakness Weakness in limb or bulbar Speech becomes nasal Swallowing difficulties Diplopia and ptosis Worsening weakness and sustained muscle contraction Tendon reflexes and sensations are normal Dysphagia Dysarthria Facial paresis
what are the signs of MG?
Ptosis Diplopia Dysarthria Head drop Limb fragility
what are the symptoms of MG?
Ocular, bulbar and limb weakness Fragility Shortness of breath Difficulty swallowing Nasal speech
what are the first line and gold standard investigations for MG?
Ice pack test - apply for 2 mins to eye, improvement of ptosis >2mm = positive
Cogan lid twitch - follow finger up, then down, then back to midline, upper eyelid will twitch up instead of stopping at midline
Antibodies AChR Ab +ve in 80 - 85%
Anti MuSK +ve in 10%
EMG - electromyography - repetitive muscle stimuli=tion rec=sults in decremental potential
Single fibre EMG - increased jitter and block
Serum pulmonary function test - myasthenic crisis: low FVC and low NIF
CT chest- 15% have thymoma
what are the differential diagnoses for MG?
Miller fisher Graves Botulism LEMS Penicillamine-induced myasthenia gravis Primary myopathies
how is MG managed?
Severe disease and crisis:
Intubation and ventilation, plasma exchange, IV immunoglobulin, corticosteroid (prednisolone), eculizumab or rituximab, Steroid sparing agents (azathioprine, ciclosporin, methotrexate, mycophenolate mofetil)
Mild disease:
Pyridostigmine (AChesterase inhibitors), corticosteroids, thymectomy, Steroid sparing agents (azathioprine, ciclosporin, methotrexate, mycophenolate mofetil)
how is MG monitored?
Patients should be followed in neurology clinics. Frequency of clinic visits depends on the severity of the disease (typically between 3 to 12 months), need for drug therapy monitoring, and presence of systemic comorbidities.
what are the complications of MG?
Pyridostigmine induced adverse reactions
Respiratory failure
Impaired swallowing
Acute aspiration
what is the prognosis of MG?
Symptomatic improvement and clinical remission are the goals of therapy. Most, but not all, patients enjoy good quality of life and normal lifespan due to advances in diagnosis and immunosuppressive treatment. However, the onset of improvement varies greatly from days to months
