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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 - PowerPoint PPT Presentation
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Myasthenia Gravis重症肌无力 (MG)
Department of Neurology Ruijin Hospital
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Outline
Introduction Etiology and PathogenesisEtiology and Pathogenesis PathologyPathology&Pathophysiology&Pathophysiology menifestationmenifestation Diagnosis&Diagnosis&Differential Differential
DiagnosisDiagnosis ManagementManagement
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Introduction Acquired autoimmune disease Inability of signal transmission within the neuro-
muscular 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
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.
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Pathology
muscles contain lymphorrhages
thymoma with MG
loss of synaptic folds and widened clefts
Muscular morphology was normal in most cases
Hypertrophy(65%)Thymoma(10-20%)
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)
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Ocular Ocular
Ptosis(dropping eyelid) – asymmetric, fatigues with upgaze
Diplopia(double vision) – most common involved MR(medial rectus )
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BulbarBulbar Dysarthria Dysphagia Dysphonia Masticatory weakness – jaw closure > jaw open
LimbsLimbs
Commonly proximal, symmetric Arms more affected than legs
Respiratory musclesRespiratory muscles
Exertional dyspnea TachypneaRespiratory failure (Myasthenic crisis)
Axial musclesAxial muscles
Neck flexionNeck extension
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MG Crisis defined as the need for assisted ventilation arises in about 10% of myasthenic patients more likely to occur in patients with dysart
hria, dysphagia, and documented respiratory muscle weakness
may also occur in other patients after respiratory infection or major surgery
Clinical Presentation -(5)
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Categorization of MG Crisis Myasthenic crisis
acetylcholine insufficiency
Cholinergic crisis
acetylcholine overmuch
Brittle crisis
non susceptivity to acetylcholine
Clinical Presentation -(5)
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crisis Myasthenic Cholinergic Brittle
incidence More often less less
perspiring little much uncertain
dribbling no much uncertain abdominal pain
no obvious no
fasciculation no obvious no
pupil normal smaller normalReaction toChEI ameliorate aggravate no reaction
atropin No reaction ameliorate no reactionPrecipitating factor
Infection delivery
ChEI over not clear
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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 , (a), (b) getting worseⅠ Ⅱ ⅡⅤ.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
Fatigue test ( Jolly test )Blink eyes for 30 consecutive times
Holding arms horizontally
Crouching for 10-20 consecutive times
Neostigmine Test1.5mg neostigmine methylsulfate for adults
Alleviation within 10-20m post injection is (+)
0.5mg atropine was simultaneously injected for
prevention of side effects
DiagnosticDiagnostic test testss
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Neostigmine testNeostigmine 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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Repetitive nerve stimulation
Single fiber electromyography
DiagnosticDiagnostic test testss
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DiagnosticDiagnostic test testss1.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 (MuS
K) 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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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
DiagnosticDiagnostic test tests-(5)s-(5)
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Diagnosis Diagnosis ProcedureProcedure
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 diagnosisDifferential diagnosis
Lambert-Eaton syndrome
Chronic inflammatory muscular disorders
Ocular muscle dystrophy
Progressive bulbar palsy
Clostridium botulinum intoxication
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ManagementManagement -(1)-(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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ManagementManagement -(2)-(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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ManagementManagement -(3)-(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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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
ManagementManagement -(-(44))
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Summary Acquired autoimmune Disease Antibodies attack the Acetylcholine receptor. the ocular, bulbar and proximal skeletal are more likely a
ffected Fatigability is a key symptom! Disease has a fluctuating pattern of ‘crises’ and remittan
ces. Treatment is usually with Acetylcholinesterase inhibitors
and immunosupression Easily treated and would have a good life expectancy.
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Thanks !