Nerdology 2 Flashcards
What is myasthenia gravis?
Autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest
Describe the epidemiology of myasthenia gravis
- More commonly affects females under 40 or males over 60- Association between thymoma and myasthenia gravis (10-20% of patients with myasthenia gravis have a thymoma, 20-40% of patients with a thymoma develop myasthenia gravis)
What are 2 causes of myasthenia gravis?
- Acetylcholine receptor (ACh-R) antibodies (85%)2. Muscle-specific kinase (MuSK) antibodies and low-density lipoprotein receptor-related protein 4 (LRP4) antibodies (15%)
Describe the pathophysiology of myasthenia gravis (due to ACh-R antibodies)?
- Antibodies bind to postsynaptic neuromuscular junction receptors- This blocks the receptor and prevents acetylcholine from being able to stimulate the receptor and trigger muscle contraction- During muscle activity, receptors become increasingly blocked up which causes less effective stimulation of muscle with increased activity- = more muscle weakness the more muscles are usedAntibodies also activate the complement system within the neuromuscular junction which leads to damage to cells at the postsynaptic membrane
Describe the pathophysiology of myasthenia gravis (due to MuSK and LRP4 antibodies)?
- Important proteins for creation and organisation of acetylcholine receptors- Destruction causes inadequate acetylcholine receptors
What is the characteristic feature of myasthenia gravis?
Weakness that gets worse with muscle use and improves with rest
What are 7 symptoms of myasthenia gravis?
- Diplopia2. Ptosis3. Weakness in facial movements4. Difficulty with swallowing5. Fatigue in jaw when chewing6. Slurred speech7. Progressive weakness with repetitive movements
What are 5 investigations for patients with myasthenia gravis?
- Check fatiguability in muscles2. Check for a thymectomy scar or CT/MRI of thymus gland3. Test forced vital capacity (FVC)4. Antibodies5. Edrophonium test
What are 3 ways of checking fatiguability in muscles?
- Repeated blinking will exacerbate ptosis2. Prolonged upward gazing with exacerbate diplopia3. Repeated abduction of one arm 20 times will result in unilateral weakness when comparing both sides
Which 3 antibodies should you test for in myasthenia gravis?
- Acetylcholine receptor antibodies (85%)2. Muscle-specific kinase antibodies (10%)3. Low-density lipoprotein receptor-related protein antibodies (<5%)
What is the edrophonium test?
- Patient given IV dose of edrophonium chloride- Acetylcholinesterase enzymes break down acetylcholine in neuromuscular junctions- Edrophonium blocks enzymes to stop the breakdown of acetylcholine- Level of acetylcholine increases- Briefly and temporarily relieves weakness in patients with myasthenia gravis
What is the treatment for myasthenia gravis?
- Reversible acetylcholinesterase inhibitors e.g. pyridostigmine, neostigmine- Immunosuppression e.g. prednisolone, azathioprine- Thymectomy- Monoclonal antibodies e.g. rituximab, eculizumab
What type of drugs are pyridostigmine and neostigmine and how do they work?
Reversible acetylcholinesterase inhibitors - increase the amount of acetylcholine in the neuromuscular junction and improve symptoms
What is rituximab and how does it work?
Monoclonal antibody - targets B cells and reduces the production of antibodies
What is eculizumab and how does it work?
Monoclonal antibody - targets complement protein C5 to reduce inflammation
What is the main complication of myasthenia gravis?
Myasthenia crisis
What does a myasthenia crisis cause?
- Acute worsening of symptoms (often triggered by another illness e.g. respiratory tract infection)- Can lead to respiratory failure
How is a myasthenia crisis treated?
- Non-invasive ventilation with BiPAP or full intubation and ventilation- Immunomodulatory therapies e.g. IV immunoglobulins and plasma exchange
What is Parkinson’s disease?
Progressive reduction of dopamine in the basal ganglia leading to disorders of movement
Describe the epidemiology of Parkinson’s disease
- Most common in older men - 2nd most common neurodegenerative disorder
What are 3 risk factors for Parkinson’s disease?
- Age2. Male3. Pesticide exposure
Describe the pathophysiology of Parkinson’s disease
- Basal ganglia are a group of structure responsible for coordinating habitual movements- Substantia nigra pars compacta is a part of the basal ganglia that produces dopamine which is essential for the correct functioning of the basal ganglia- Parkinson’s = gradual fall in the production of dopamine (impaired nigrostriatal pathway)
What is the classic triad for Parkinson’s disease?
- Resting unilateral tremor2. ‘Cogwheel’ rigidity3. Bradykinesia
How does a Parkinson’s tremor differ from a benign essential tremor?
- Asymmetrical- 4-6 Hz frequency- ‘Pill rolling’ tremor- Improves on voluntary movement- Worsened if patient is distracted- No change with alcohol