Muscle Disease and Myasthenia Gravis Flashcards
Definition - Myasthenia Gravis.
Autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest.
Association - Thymomas and Myasthenia Gravis
10-20% of patients with Myasthenia Gravis have a Thymoma (or 50-70% - thymic hyperplasia).
20-40% of patients with a Thymoma develop Myasthenia Gravis.
Myasthenia Gravis vs. Lambert-Eaton Myasthenic Syndrome (5).
- Definition : MG & LEMS - Progressive muscle weakness as a result of damage at the NMJ.
- Course : MG - More insidious and less pronounced symptoms.
- Association : MG - Thymoma. LEMS - SCLC.
- Antibodies : MG - Anti-ChR, Anti-MuSK, Anti-LPR4. LEMS - Anti-VGCC (in presynaptic terminals of NMJ).
- Muscle Weakness : MG - Facial and Ocular Muscles. LEMS - Proximal Limb Weakness (Legs > Arms).
What is Post-Tetanic Potentiation?
Reflexes become temporarily normal for a short period following a period of strong muscle contraction but are otherwise reduced.
This is a feature of LEMS.
Epidemiology of Myasthenia Gravis (3).
- Men : >60.
- Women : <40.
- 2x Women : Men.
Clinical Features of Myasthenia Gravis (5).
- Weakness worsens with activity and improves with rest (minimal in morning and worse at the end of the day).
- Proximal Muscles and Small Muscles of Head and Neck.
- Diplopia (Extraocular - Double Vision).
- Ptosis (Eyelid - Drooping).
- Weakness in Facial Movements, Swallowing, Chewing, Slurred Speech.
Pathophysiology of Myasthenia Gravis.
85% : Anti-AChR antibodies bind to post-synaptic receptors at NMJ to prevent ACh functioning. As the receptors are used more during muscle activity, most of them will become blocked up, leading to less effective stimulation of the muscle with increased activity. Antibodies also activate the Complement at the NMJ to damage post-synaptic membrane cells.
15% : Anti-MuSK (Muscle Specific Kinase) or Anti-LRP4 (Low-Density Lipoprotein Receptor-Related Protein 4).
MuSK and LRP4 are responsible for the creation and organisation of the AChR.
Examination of Myasthenia Gravis (3C).
- Thymectomy Scar.
- FVC.
- Fatiguability
A. Repeated Blinking - Ptosis Exacerbation.
B. Prolonged Upward Gazing - Diplopia Exacerbation.
C. Repeated Abduction of One Arm 20x - Weakness Exacerbation.
Investigations of Myasthenia Gravis.
- Bloods - CK is not raised (no muscle damage).
- CT Thorax - exclude Thymoma.
- Single Fibre Electromyography (high sensitivity).
- Bloods - Measure Antibodies (Anti-AChR; Anti-MuSK; Anti-LRP4).
Single Fibre Electromyography.
Needles are inserted into the muscles to measure electrical activity - typically around the eyes, forehead, arms. Electrical recordings can show whether signals sent to muscles from nerves are being disrupted.
Tensilon/Edrophonium Test.
Patients are given an IV dose of Edrophonium Chloride/Neostigmine. Usually, AChEs in the NMJ break down Ach. Edrophonium blocks AchEs at the NMJ so ACh levels rise, giving a brief and temporary relief of muscle weakness.
This is no longer use due to the risk of cardiac arrhythmias.
Treatment Options in Myasthenia Gravis (4).
- Reversible AChE Inhibitors e.g. Pyridostigmine, Neostigmine.
- Immunosuppression e.g. Prednisolone, Azathioprine, Cyclosporine, Mycophenolate Mofetil.
- Thymectomy.
- Monoclonal Antibodies.
Reversible Acetylcholinesterase Inhibitors - Adverse Effects (7).
- Hypersalivation.
- Lacrimation.
- Sweats.
- Vomiting.
- Miosis.
- Diarrhoea.
- Colic.
Monoclonal Antibodies - Mechanism of Action (2).
- Rituximab - targets B cells to reduce the production of antibodies (NHS if standard treatment is not effective).
- Eculizumab - targets C5 Complement Protein to prevent Complement activation and destruction of AChR (NICE do not currently recommend it).
Definition of Myasthenic Crisis.
A severe life-threatening complication : acute worsening of symptoms triggered by another illness e.g. RTI - leads to respiratory failure.
Management of MyastheniC Crisis.
- Immunomodulatory Therapy e.g. IVIG, Plasma Exchange.
2. NIV - BiPAP, Full Intubation and Ventilation.