Myasthenia gravis

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Lecture myashtenia gravis

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Myasthenia gravis

  1. 2. Neuropsychiatry Department Prof Aymen Youssef Ezz El Din <ul><li>Prof OMAR AL GAREM </li></ul><ul><li>Prof. Salah Al Din Mansour </li></ul><ul><li>Prof. Mohammed Al Fatatry </li></ul><ul><li>Prof Farouk Talaat </li></ul><ul><li>Prof. Nadia Hafez </li></ul><ul><li>Prof Ahmed Deif </li></ul><ul><li>Prof Mohammed Ramadan </li></ul><ul><li>Prof Soliman Tahoon </li></ul><ul><li>Prof. Mohammed Foad </li></ul><ul><li>Prof Abd Al Fattah Al Kersh </li></ul><ul><li>Prof Lubna Sultan </li></ul><ul><li>Prof Ashraf Abdou </li></ul><ul><li>Prof Sameh Saeed </li></ul><ul><li>Ass Prof Ismael Ramadan </li></ul><ul><li>Ass Prof Hazem Marouf </li></ul><ul><li>Ass Prof Mohammed Hamdy </li></ul><ul><li>AA Prof Horya Saad </li></ul><ul><li>Dr Doaad Hanafy </li></ul><ul><li>Dr Gadaa Abd Al Hady </li></ul><ul><li>Dr Mervat </li></ul><ul><li>Prof Siham Rashid </li></ul><ul><li>Prof Ade Al Shashae </li></ul><ul><li>Prof Hoda Salama </li></ul><ul><li>Prof Mostafa Al Sadani </li></ul><ul><li>Ass Prof Manal Hassan </li></ul><ul><li>Ass Prof Tarek Molukhia </li></ul><ul><li>Ass Prof Afaf </li></ul><ul><li>Ass Prof Maha Al Taybany </li></ul><ul><li>Dr Soha Ghobashy </li></ul><ul><li>Dr Osama Al kholy </li></ul><ul><li>Dr Ahmed Rady </li></ul>Dr Amr Al Fatatry Dr Jaeda Mekky Dr Heba Essam Dr Hisham Sheshtawy Dr Hisham Abud 2008-09
  2. 3. http://groups.google.com/group/alexneuropsych E-mail: [email_address] [email_address]
  3. 4. Myasthenia Gravis: Update Dr Ashraf Abdou Professor Neuropsychiatry dept
  4. 5. Clinical <ul><li>Myasthenia gravis (MG) is a neuromuscular junction transmission disorder characterized by muscle weakness and fatigue. </li></ul><ul><li>Peaks around the 2 nd and 3 rd decades and the 6 th and 7 th decades of life. </li></ul><ul><li>The prevalence of myasthenia gravis ranges between 4-14/100,000. </li></ul>[Orphan disease]
  5. 6. Incidence <ul><li>1 in 20 000 </li></ul><ul><li>No racial or geographical prediliction </li></ul><ul><li>Any age although rare in <2yrs </li></ul><ul><li>Peaks incidence in young females </li></ul><ul><li>Females x2 males </li></ul><ul><li>Gender preference diminishes with increasing age </li></ul><ul><li>Smaller second peak in elderly males </li></ul>
  6. 9. Cholinesterase Inhibitors
  7. 10. Myasthenia Gravis is an autoimmune Disease that is characterized by a decrease in number of AChR Because there are fewer AChR to bind to the end plate potentials (EPPs) are smaller. With smaller EPPs the “ safety factor” is reduced there is less chance that the post-synaptic muscle fibres will be activated
  8. 11. Note: The amplitude of the end plate-potential is directly related to the amount of ACh that binds to the post-synaptic AChRs.
  9. 12. Pathophysiology <ul><li>IgG AB interact with the postsynaptic AChR at the nicotinic neuromuscular junction(NMJ). </li></ul><ul><li>This reduces the number of functional receptors by blocking Ach attachment, by increasing the degradation of receptors and by complement induced damage to the NMJ </li></ul><ul><li>MG pts have a reduced AChR density and have 30% the normal number of AChR </li></ul><ul><li>This reduces the safety margin at the NMJ </li></ul>
  10. 13. Etiology <ul><li>Antibody mediated, origin uncertain </li></ul><ul><li>Thymus gland possible generator </li></ul><ul><li>Gland abnormal in 75% of patients with MG( hyperplasia and thymoma) </li></ul><ul><li>B and T lymphocytes become sensitised to AChR found in myoid cells in the gland </li></ul><ul><li>Reason for breakdown in normal immune tolerance uncertain </li></ul>
  11. 15. Clinical features <ul><li>Voluntary muscle weakness cardinal feature, with fatigability, relieved with rest </li></ul><ul><li>15% pts have disease confined to the eyes </li></ul><ul><li>85% generalized ocular, facial, bulbar, limb </li></ul><ul><li>Respiratory muscles affected mildly however in myasthenic crisis resp failure requiring support may be required </li></ul><ul><li>Symptoms of diplopia, ptosis, dysarthria, regurgitation, dysphagia are all common. </li></ul>
  12. 16. Clinical [cont.] <ul><li>The salient clinical features of myasthenia gravis are skeletal muscle weakness and fatigability. Symptoms are usually aggravated by physical activity and relieved by rest. </li></ul><ul><li>60% starts in the ocular muscles , with ptosis and/or diplopia. </li></ul><ul><li>15% remain confined to the eye muscles. 85% weakness spreads to facial, bulbar, and limb muscles. </li></ul>
  13. 17. Diagnosis and Ix <ul><li>History and examination </li></ul><ul><li>EMG </li></ul><ul><ul><li>Recording of compound muscle action potentials(CMAP) </li></ul></ul><ul><ul><li>Following repetitive stimulation of motor nerve </li></ul></ul><ul><ul><li>In MG this leads to reduction in CMAP (>10%) </li></ul></ul>
  14. 18. Diagnosis <ul><li>Edrophonium or prostigmine test. </li></ul><ul><li>EMG: Repetitive nerve stimulation. </li></ul>
  15. 19. <ul><li>Detection of anti-AChR antibodies </li></ul><ul><ul><li>In 80-85% cases and are pathognomonic </li></ul></ul><ul><li>The Tensilon test- </li></ul><ul><ul><li>up to 10mg edrophonium is administered IV is standard test. </li></ul></ul><ul><ul><li>Mg pts show marked improvement after 30sec and lasts 5min </li></ul></ul>
  16. 20. Cholinesterase Inhibitors <ul><li>Examples: Neostigmine, edrophonium. </li></ul><ul><li>Mechanism of Action : Inhibit acetylcholinesterase </li></ul><ul><li>Therapeutic Use: </li></ul><ul><li>Antidote for nondepolarizing blockers </li></ul><ul><li>Treatment of myasthenia gravis (neostigmine) </li></ul><ul><li>Diagnosis of myasthenia gravis (edrophonium) </li></ul>
  17. 21. Myasthenia Gravis
  18. 22. Evidence based long-term management of MG <ul><li>Few controlled studies. </li></ul><ul><li>Most are case series and expert-opinions. </li></ul>
  19. 23. Immunomodulatory therapy <ul><li>Short term: </li></ul><ul><ul><li>Plasmapheresis. </li></ul></ul><ul><ul><li>IVIG. </li></ul></ul><ul><li>Long term: </li></ul><ul><ul><li>Thymectomy. </li></ul></ul><ul><ul><li>Imminusuppresant drugs. </li></ul></ul>
  20. 24. Immunomodulatory therapy [Short-term] <ul><li>Plasmapheresis. </li></ul><ul><li>IVIG </li></ul>When acute temporary improvement is needed.
  21. 25. IVIG <ul><li>0.4 mg/kg for 3 or 5 consecutive days. </li></ul><ul><li>Effect seen 4 days to 2 weeks after Rx and lasts 1-2 months. </li></ul>
  22. 26. Plasmapheresis <ul><li>6 sessions, every other day. </li></ul><ul><li>Improvement during treatment and the 1 st week after treatment. </li></ul><ul><li>Improvement last 1-2 months. </li></ul>
  23. 27. Immunomodulatory therapy [long-term] <ul><li>Thymectomy. </li></ul><ul><li>Immunomodulatory drugs. </li></ul>To induce remission
  24. 28. Thymectomy <ul><li>Quality Standard guidelines of AAN 2000 </li></ul><ul><li>For patients with nonthymomatous autoimmune MG, thymectomy is recommended as an option to increase the probability of remission or improvement. </li></ul><ul><li>What age? </li></ul><ul><li>those with disease onset after the age of 60 rarely have substantial improvement from thymectomy. </li></ul>
  25. 29. Thymectomy [cont.] <ul><li>Thymoma : Do thmectomy due to risk of invasive thymoma, heart and lung damage, phrenic nerve damage, and other problems. </li></ul><ul><li>Acetylcholine receptor antibodies : thymectomy may help. </li></ul><ul><li>MUSK antibodies : thymectomy does not help. </li></ul><ul><li>No antibodies : unknown if thymectomy helps. </li></ul>
  26. 30. Immunomodulatory Drugs [Long-term] <ul><li>Corticosteroids.[15 $/month] </li></ul><ul><li>Azathioprine.[70-140$/month] </li></ul><ul><li>Methotrexate [10-25 mg q week – 13-30$/month] </li></ul><ul><li>Mycophenolate mofetil (CellCept). [1g BID – 400-600$/month] </li></ul><ul><li>Cyclosporine A [5 mg/kg BID – 400-600$/month] </li></ul><ul><li>Cyclophosphamide. [20 mg q week IV – 100-300$/month] </li></ul>
  27. 31. We should WAIT 1-2 months Cellcept 1-3 months Methotraxate 6-8 months Azathioprine 1-3 months Corticosteroids One year Thymectomy
  28. 33. THANK YOU

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