Transcript Myasthenia Gravis 重症肌无力

Myasthenia Gravis
重症肌无力(MG)
Department of Neurology
Ruijin Hospital
1
Outline






Introduction
Etiology and Pathogenesis
Pathology&Pathophysiology
menifestation
Diagnosis&Differential
Diagnosis
Management
2
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
3
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
5
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 )
9
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
10
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
11
Clinical Presentation -(5)
Categorization of MG Crisis

Myasthenic crisis


Cholinergic crisis


acetylcholine insufficiency
acetylcholine overmuch
Brittle crisis

non susceptivity to acetylcholine
12
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
13
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.
14
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
15
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.)
17
Diagnostic tests


Repetitive nerve
stimulation
Single fiber
electromyography
18
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
19
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
20
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
21
Differential diagnosis

Lambert-Eaton syndrome

Chronic inflammatory muscular disorders

Ocular muscle dystrophy

Progressive bulbar palsy

Clostridium botulinum intoxication
22
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
23
Management -(2)

Thymus-targeted therapy
indication
thymoma, hypertrophy of thymus, drug-resistant patients
contra-indication
<18y, non-severe
effective for 70% patients
sometimes worsens
24
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
25
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
26
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.
27
Thanks！
28