Myasthenia Gravis 重症肌无力
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Transcript Myasthenia Gravis 重症肌无力
Myasthenia Gravis
重症肌无力(MG)
Department of Neurology
Ruijin Hospital
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Outline
Introduction
Etiology and Pathogenesis
Pathology&Pathophysiology
menifestation
Diagnosis&Differential
Diagnosis
Management
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Introduction
Acquired autoimmune disease
Inability of signal transmission within the neuromuscular junction (NMJ)
Clinically characterized by:
Fatigue of skeletal muscles
Deterioration on movement
Alleviation on cholinesterase inhibitors
Incidence: (0.5-5)/100,000
Prevalence: 10/100,000
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Etiology and Pathogenesis
Normally when impulses travel down the nerve,
the nerve dendings resealse a neurotransmitter
substance called acetylcholine, Ach tracels
through the neuromuscular junction and binds to
Ach receptors which are activited and generate a
muscle constration.
The chronic inflammation of MG causes several
changes in the structure of the Neuromuscular
Junction which also inhibit transmission and
contribute to weakness. These include flattening
out of the junctional folds, spreading out of AChR
and Acetylcholinesterase, a 66% decrease in
number of AChR, and an increased junctional gap.
Pathology
Muscular morphology was normal in most cases
loss of synaptic folds and widened clefts
thymoma with MG
Hypertrophy(65%)
Thymoma(10-20%)
muscles contain lymphorrhages
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Clinical Presentation-(1)
MG occurs at any age
Onset summit: 20-40y(F>M), 40-60y(M>F)
10% onset before 10y
Thymoma was frequently seen in late onset patients
Mostly insidious and progressive
Muscle weakness
Clinical Presentation-(3)
Weakness could be seen in all skeletal muscles.
Ptosis,diplopia,oropharyngeal muscle weakness –
difficulty in swallowing and talking, or limb
weakness
fluctuates and progressively worsens over course of day
worsens with prolonged use of affected muscles (i.e. fatiguable)
Ocular
Ptosis(dropping eyelid) –
asymmetric, fatigues with
upgaze
Diplopia(double vision) –
most common involved
MR(medial rectus )
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Bulbar
Respiratory muscles
Dysarthria
Dysphagia
Dysphonia
Masticatory weakness
– jaw closure > jaw open
Exertional dyspnea
Tachypnea
Respiratory failure
(Myasthenic crisis)
Limbs
Axial muscles
Commonly
Neck flexion
Neck extension
proximal, symmetric
Arms more affected than legs
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Clinical Presentation -(5)
MG Crisis
defined as the need for assisted ventilation
arises in about 10% of myasthenic patients
more likely to occur in patients with
dysarthria, dysphagia, and documented
respiratory muscle weakness
may also occur in other patients after
respiratory infection or major surgery
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Clinical Presentation -(5)
Categorization of MG Crisis
Myasthenic crisis
Cholinergic crisis
acetylcholine insufficiency
acetylcholine overmuch
Brittle crisis
non susceptivity to acetylcholine
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crisis
Myasthenic
Cholinergic
Brittle
incidence
perspiring
dribbling
More often
little
no
no
less
much
much
obvious
less
uncertain
uncertain
no
fasciculation no
obvious
no
pupil
smaller
aggravate
ameliorate
normal
no reaction
no reaction
not clear
abdominal
pain
Reaction toChEI
atropin
Precipitating
factor
normal
ameliorate
No reaction
Infection
delivery
ChEI over
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Osserman Classification of MG-(1)
Based on the severity of the disease
1、Adult MG
Ⅰ.Ocular myasthenia(15-20%)
Ⅱ(a).Generalized MG of mild intensity(30%)
Ⅱ(b) .Generalized MG of moderate intensity(25%)
Ⅲ.Severe generalized disease(15%) with respiratory failure: Intubation
needed to maintain airway
Ⅳ. generalized disease due to type Ⅰ,Ⅱ(a),Ⅱ(b) getting worse
Ⅴ.Myasthenic Gravis with muscle atrophy in early stage.
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Osserman Classification of MG-(2)
2、Childhood MG (account for 20% in Chinese MG patients)
(1) Neonatal MG: most cases recovered after 1w to 3ms’ treatment
(2) Congenital MG: mostly resistant to AchR inhibitors; family history
3、Teenager MG: onset from 14y to 18y.
Most cases only presented with ocular symptoms
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Diagnostic tests
Fatigue test(Jolly test)
Blink eyes for 30 consecutive times
Holding arms horizontally
Crouching for 10-20 consecutive times
Neostigmine Test
1.5mg neostigmine methylsulfate for adults
Alleviation within 10-20m post injection is (+)
0.5mg atropine was simultaneously injected for
prevention of side effects
Neostigmine test
A: Severe ptosis of the
lids.
B: Same patient 1 minute
after intravenous injection
of edrophonium (10 mg).
(From Rowland LP,
Hoefer PFR, Aranow H Jr.
Myasthenic syndromes.
Res Publ Assoc Res Nerv
Ment Dis 1961;38; with
permission.)
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Diagnostic tests
Repetitive nerve
stimulation
Single fiber
electromyography
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Diagnostic tests
1.Antibodies to AChR
generalized MG :>80%
iocular MG:50%
MG and thymoma:98-100%
The titer does not match the severity of symptoms
2. Anti-muscle specific receptor tyrosine kinase (MuSK)
antibodies
Used if MG suspected, patient seronegative
Present
in 40–50% of seronegative patients with
generalized MG; absent in ocular MG
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Diagnostic tests-(5)
Radiographs of the
chest provide
evidence of
thymoma in about
15% of patients,
especially in those
older than 40 years.
CT of the
mediastinum
demonstrates all but
microscopic
thymomas.
thymoma
hyperplasia of the thymus
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Diagnosis Procedure
When to suspect?
Fluctuating Weakness
Better in the morning, worse in the afternoon
Positive fatigue test
How to confirm?
Neostigmine test
Repetitive nerve stimulation
SFEMG
Anti-AchR antibody titters
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Differential diagnosis
Lambert-Eaton syndrome
Chronic inflammatory muscular disorders
Ocular muscle dystrophy
Progressive bulbar palsy
Clostridium botulinum intoxication
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Management -(1)
Management with medicine
Anticholinesterase drug(Mestinon max60mg,q4h)
Cortisones(could
worsen the disease in short term,
side effects could be fatal)
Immune suppress agents(
azathioprine,
cyclophosphamide, cyclosporine A, etc)
Contraindicated drugs
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Management -(2)
Thymus-targeted therapy
indication
thymoma, hypertrophy of thymus, drug-resistant patients
contra-indication
<18y, non-severe
effective for 70% patients
sometimes worsens
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Management -(3)
Plasmapheresis
remove Ach-R antibodies of serum
effective but not consistent
used in case of MG crisis
Intravenous Immunoglobulin (IVIg)
effective
side effects were rare
widely used in clinical practice
0.4g/(kg d), iv. 3-5 days/course
interfere the function of Ach-R antibodies
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Management -(4)
Artificially facilitated breath is urgently needed
Anti-infection therapy is frequently needed
Cortisones
Myasthenia Crisis: increase doses of neostigmine
Choligernic Crisis: stop using neostigmine
Brittle Crisis: stop using neostigmine
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Summary
Acquired autoimmune Disease
Antibodies attack the Acetylcholine receptor.
the ocular, bulbar and proximal skeletal are more likely
affected
Fatigability is a key symptom!
Disease has a fluctuating pattern of ‘crises’ and
remittances.
Treatment is usually with Acetylcholinesterase inhibitors
and immunosupression
Easily treated and would have a good life expectancy.
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Thanks!
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