myasthenia gravis
DESCRIPTION
Lecture myashtenia gravisTRANSCRIPT
Myasthenia Gravis: Update
Dr Ashraf AbdouProfessor Neuropsychiatry dept
Clinical
Myasthenia gravis (MG) is a neuromuscular junction transmission disorder characterized by muscle weakness and fatigue.
Peaks around the 2 nd and 3 rd decades and the 6 th and 7 th decades of life.
The prevalence of myasthenia gravis ranges between 4-14/100,000.
[Orphan disease]
Incidence
1 in 20 000No racial or geographical predilictionAny age although rare in <2yrsPeaks incidence in young femalesFemales x2 malesGender preference diminishes with increasing ageSmaller second peak in elderly males
Cholinesterase Inhibitors
Myasthenia Gravis is an autoimmune Disease that ischaracterized 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
Note: The amplitude of the end plate-potential is directly related to the amount of ACh that binds to the post-synaptic AChRs.
Pathophysiology Pathophysiology • IgG AB interact with the postsynaptic
AChR at the nicotinic neuromuscular junction(NMJ).
• 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
• MG pts have a reduced AChR density and have 30% the normal number of AChR
• This reduces the safety margin at the NMJ
Etiology Etiology
• Antibody mediated, origin uncertain• Thymus gland possible generator• Gland abnormal in 75% of patients with
MG( hyperplasia and thymoma)• B and T lymphocytes become sensitised
to AChR found in myoid cells in the gland
• Reason for breakdown in normal immune tolerance uncertain
Clinical featuresClinical features
• Voluntary muscle weakness cardinal feature, with fatigability, relieved with rest
• 15% pts have disease confined to the eyes• 85% generalized ocular, facial, bulbar, limb• Respiratory muscles affected mildly however
in myasthenic crisis resp failure requiring support may be required
• Symptoms of diplopia, ptosis, dysarthria, regurgitation, dysphagia are all common.
Clinical [cont.]
The salient clinical features of myasthenia gravis are skeletal muscle weakness and fatigability. Symptoms are usually aggravated by physical activity and relieved by rest. 60% starts in the ocular muscles, with ptosis and/or diplopia.
15% remain confined to the eye muscles. 85% weakness spreads to facial, bulbar, and limb muscles.
Diagnosis and Ix
History and examinationEMG
Recording of compound muscle action potentials(CMAP)Following repetitive stimulation of motor nerveIn MG this leads to reduction in CMAP (>10%)
Diagnosis
Edrophonium or prostigmine test.
EMG: Repetitive nerve stimulation.
Detection of anti-AChR antibodies
In 80-85% cases and are pathognomonic
The Tensilon test- up to 10mg edrophonium is administered IV is standard test.Mg pts show marked improvement after 30sec and lasts 5min
Cholinesterase Inhibitors
• Examples: Neostigmine, edrophonium.• Mechanism of Action: Inhibit acetylcholinesterase
• Therapeutic Use: • Antidote for nondepolarizing blockers• Treatment of myasthenia gravis (neostigmine)• Diagnosis of myasthenia gravis (edrophonium)
Myasthenia Gravis
Evidence based long-term management of
MG
•Few controlled studies.•Most are case series and expert-opinions.
Immunomodulatory therapy
Short term:Plasmapheresis.IVIG.
Long term:Thymectomy.Imminusuppresant drugs.
Immunomodulatory therapy
[Short-term]Plasmapheresis.
IVIG
When acute temporary improvement is needed.
IVIG
0.4 mg/kg for 3 or 5 consecutive days.
Effect seen 4 days to 2 weeks after Rx and lasts 1-2 months.
Plasmapheresis
6 sessions, every other day.
Improvement during treatment and the 1st week after treatment.
Improvement last 1-2 months.
Immunomodulatory therapy [long-term]
Thymectomy.
Immunomodulatory drugs.
To induce remission
Thymectomy
Quality Standard guidelines of AAN 2000
For patients with nonthymomatous autoimmune MG, thymectomy is
recommended as an option to increase the probability of remission or improvement.
What age?those with disease onset after the age of 60
rarely have substantial improvement from thymectomy.
Thymectomy [cont.]
Thymoma: Do thmectomy due to risk of invasive thymoma, heart and lung damage, phrenic nerve damage, and other problems.
Acetylcholine receptor antibodies: thymectomy may help.MUSK antibodies: thymectomy does not help.No antibodies: unknown if thymectomy helps.
Immunomodulatory Drugs[Long-term]
Corticosteroids.[15 $/month]Azathioprine.[70-140$/month]Methotrexate [10-25 mg q week – 13-30$/month]Mycophenolate mofetil (CellCept). [1g BID – 400-600$/month]Cyclosporine A [5 mg/kg BID – 400-600$/month] Cyclophosphamide. [20 mg q week IV – 100-300$/month]
We should WAITThymectomyOne year
Corticosteroids1-3 months
Azathioprine6-8 months
Methotraxate1-3 months
Cellcept1-2 months
THANK YOUTHANK YOU