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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 ！