Mind Map Gallery Myasthenia Gravis
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Myasthenia Gravis
This is a mind map of myasthenia gravis. You can make and share your own mind maps easily. Just try EdrawMind mind mapping software for free! Myasthenia gravis (MG) is a chronic autoimmune disorder in which antibodies destroy the communication between nerves and muscle, resulting in weakness of the skeletal muscles. Myasthenia gravis affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.
Edited at 2023-02-16 01:35:02
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Myasthenia Gravis
Over view
a chronic, fluctuating, antibody-mediated autoimmune disorder
directed against the post-synaptic neuromuscular junctions of skeletal muscles
resulting in a wide spectrum of manifestations ranging from mild to potentially fatal
characterized by weakness and rapid fatigability of skeletal muscle
the patient is unable to maintain voluntary muscular contraction for more than brief periods
Pathophysiology of MG
In this disease, antibodies are produced against the main immunogenic region found on α1 subunits of the nicotinic receptor-channel complex.
Antibodies are detected in 85% of myasthenic patients
The antibodies reduce nicotinic receptor function in many ways
Cross-linking receptors, a process that stimulates their internalization and degradation
Causing lysis of the postsynaptic membrane; and Binding to the nicotinic receptor and inhibiting function
Reduced postsynaptic nicotinic (Nm)Rs normal muscles receptor density
Results in end-plate potentials of diminished amplitude which fail to
trigger action potentials in some fibres causing a failure in initiation of muscle fibre contraction – power of the whole muscle is reduced
The amount of ACh released per impulse normally declines on repeated activity (termed presynaptic rundown)
Etiology and Epidemiology of MG
IgG antibodies attack Ach nicotinic NmRs on SK. muscles.
Antibody-antigen complex and inflammation inhibit neuromuscular transmission.
Breakdown of immune tolerance involves thymus.
Afffects Women > men before age 50.
Peak onset 20-40 years
Men more commonly diagnosed ages 60-80.
It also occurs in children and adolescents.
MG is a hereditary disease transmitted genetically from parents.
Clinical Features of MG
Painless, Fluctuating weakness of voluntary muscles (fatigability)
Worsen after exertion and improve with rest.
Exacerbating factors include
emotional stress
rapid changes in body temperature
infection
trauma
multiple medications
Ocular manifestations is common
diplopia
ptosis
Ocular MG 10-40% of all cases
Generalized MG symptoms vary based on muscle groups
oropharyngeal
skeletal
respiratory
Ocular symptoms
Initial symptoms involve the ocular muscles in 60% of cases
All patients will have ocular involvement within 2 years of disease onset
Ocular manifestations
Ptosis
uni- or bilateral is very common and may occur while patients reading, or during long period of driving
Diplopia
Extraocular muscle weakness may also present asymmetrically
Limb muscles weakness
Initial symptoms in fewer than 10%
Upper extremities weakness is more common than lower extremities, asymmetrical.
Involve proximal muscles than distal
Involve neck muscles: neck flexion weaker than neck extension
Respiratory insufficiency
The initial presentation is rare
Occurring precipitously in a patient with recent worsening of symptoms
MG: Classification
MG Foundation of America Clinical Classification
Grade I: Any ocular muscle weakness
Grade II: Mild weakness affecting other than ocular muscles
IIa: limb and/or axial weakness; less oropharyngeal involvement
IIb: oropharyngeal and/or respiratory weakness
Grade III: Moderate weakness affecting other than ocular muscles (a,b)
Grade IV: Severe weakness affecting other than ocular muscles (a,b)
Grade V: Defined by tracheal intubation.
Myasthenia Gravis: Diagnosis
Clinical manifestations
chronic intermittent muscle weakness;
Fatigability.
Provocative test
Physiologic tests
Look up for several minutes; counting aloud to100; repetitively testing the proximal muscles
Pharmacological tests
Pharmacological test
Curare test
to demonstrate generalized MG
Edrophonium test
Using edrophonium chloride: short acting acetylcholinesterase inhibitor
10 mg of edrophonium (0.15-0.2 mg/kg, iv) used
It causes rapid dramatic improvement of MG symptoms
A small test dose (2 mg) iv; If after 1 min. no improvement and side effect appeared, the remainder given slowly.
The effect of edrophonium: appears in 30 sec. and last fewer than 10 min.
Treatment
The goal is to achieve remission
Goal
Symptoms free and taking no medication
By increased neuromuscular transmission
Reduce autoimmunity
Others: having a normal quality of life even if some signs
remaining and cholinesterase inhibitors taking
No single treatment is ideal for all patients
Each patient needs an individual plan
Treatment may have to be changed time to time
Types of Mg therapy
Symptomatic therapy
Acetylcholinesterase (AChE) inhibitors
Immune-directed therapy
Corticosteroids (high dose Prednisolone 100 mg/day)
Non-steroid immunomodulators
Azathioprine
Mycophenolate mofetil
Cyclosporine
Cyclophosphamide
Tacrolimus
Rituximab
Acetylcholinesterase inhibitors (AChEIs)
Ex Neostigmine, Pyridostigmine
Benefit most patients but incomplete after weeks or months treatment; require further therapeutic measures
Ex Neostigmine, Pyridostigmine
Mechanism
Synthetic acetylcholinesterase inhibitors, inhibit the hydrolysis of the acetylcholine neurotransmitter in the synaptic cleft
These agents increase the number of interactions between the acetylcholine and the acetylcholine Nm receptors in the neuromuscular junction.
AChEIs do not cross the blood–brain barrier, thereby limiting central nervous system toxicity, and may be mildly effective in ocular and generalized MG.
Pyridostigmine (Mestinon)
This compound, which structurally resembles neostigmine, share its pharmacological actions
It has, longer duration of action and lower incidence of side effects
It is used in the treatment of myasthenia gravis
Ambenonium (Mytelase)
This is a synthetic quaternary ammonium compound
has longer duration of action and lower incidence of side effects than neostigmine
It is available for oral use in the treatment of myasthenia gravis in a dose of 10-30 mg every 4 hours
Edrophonium (Tensilon)
Edrophonium, structurally related to neostigmine
has a rapid onset and a brief duration of action
It is used in the diagnosis of suspected cases of myasthenia gravis.
and in the treatment of curare poisoning (10 mg I.V. repeated as required)
It can also be used to terminate attacks of paroxysmal supraventricular tachycardia.
Other uses of AChEIs
Antidote to competitive neuromuscular blockers
To hasten recovery from respiratory paralysis produced by overdose from competitive neuromuscular blocking agents (e.g. d-tubocurarine) , neostigmine 1-3 mg I.V. combined with 0.6-1.2 mg atropine may be used
Side effects
The reversible anti-ChE produce side effects attributable mainly to their muscarinic actions
salivation
sweating
lacrimation
diarrhea
sense of constriction in the chest
abdominal cramps
bradycardia and hypotension
Contraindications
Bronchial asthma.
Peptic ulcer.
Coronary insufficiency.
Hyperthyroidism.
Other Treatment of MG
Acute management therapies
Plasmapheresis (plasma transfusion)
IV IG Infusion
Surgical intervention (Thyroidectomy) .
Cholinergic crisis (Ch-Cr)
It is a condition results from toxicity by anticholinesterases agents either the reversible or the irreversible (organophosphate-OPC) groups.
Its Symptoms similar to that of MG including; fatigue, muscle weakness, and even paralysis.
Differential diagnosis of (Ch-Cr from MG)
Clinical investigation
Ch-Cr is accompanied with progressive muscarinic symptoms (salivation, lacrimation, colic, bradycardia,…etc)
Edrophonium (eserine) test
(5 mg/kg I.V.)
If the case is MG
Improvement of symptoms
If the case is Ch-Cr
Worsening the symptoms