MYASTHENIA GRAVIS

Definition

 An autoimmune disease, which underlying defect

is a decrease in the number of available AchR at
NMJ due to an antibody mediated autoimmune
attack (post sinaps)
 characterized by weakness and fatigability of
skeletal muscles
Pathophysiology

 The neuromuscular abnormalities caused by

an autoimmune response mediated by
specific anti AChR antibodies
 These antibodies reduce the available AChR’s
at neuromuscular junctions
Severity (Osserman classification)

 I: Ocular myasthenia
 IIA: Mild generalized myasthenia with slow
progression: no crises, responsive to drugs
 IIB. : Moderately severe generalized myasthenia :
severe skeletal and bulbar involvement but no
crises; drug response less than satisfactory
 III: Acute fulminating myasthenia, rapid
progression of severe symptoms, with respiratory
crises and poor drug response
 IV: Late severe myasthenia, same as III but
progression over 2 years from class I to II
Pathology

 The neuromuscular abnormalities in MG are

brought about by an autoimmune response
mediated by specific anti-AChR antibodies
 the thymus is abnormal in approximately 75%
of patients with MG
 In 65% of patients the thymus is hyperplastic
Clinical Features

 Prevalence rate 1 in 10,000 people

 Can affect any age group
 women - peak incidence 20’s-30’s
 men - peak incidence 50’s-60’s
 Women affected more than men
 Cardinal features - weakness and fatigability
History

 Weakness typically increases during repeated

use (fatigue) and improve during rest or sleep
 Eye lid closure, double vision after reading for
a long time or in the afternoon
 Difficulty of swallowing or slurred speech
 Difficulty of breathing
 Physical Exam

 Motor exam  weakness occur after long

contraction (especially proximal muscles)
 deep tendon reflexes are preserved
 diplopia and ptosis
 Dysphagia, dysartria
 Vocal chord test  coarse voice after reading out
loud >3 minutes (dysphonia)
Physical Exam

 Ice pack test

 Simpson’s test
 Cogan test
Simpson’s test
Cogan test
 Diagnosis and Evaluation

 Clinical features
 No loss of reflexes or impairment of sensation
or other neurologic function
 Edrophonium- initial dose 2mg IV, second dose
8mg IV (Tensilon test)
 ACh receptor antibody detectable in 80% of all
myasthenic patients
Diagnosis & evaluation

 CXR and Thorax CT

scan  thymoma +
Electrodiagnostic study

 RNS (repetitive nerve

stimulation)
 >10% decrement
 Single fiber (if RNS
normal) jitter
Differential Diagnosis

 Several other conditions that cause weakness

or the cranial and/or somatic musculature
must be considered in the differential
diagnosis of MG:
 Lambert-Eaton myasthenic syndrome, GBS,
peripheral neuropathy, periodic paralysis,
botulism, poliomyositis
Possible causes of myasthenic crisis

 Drug use : streptomycin, neomycine, curare, kina,

quinidine, chloroform, ether, morphin, sedatives,
muscle relaxan,
 infection
 delivering baby
 Excessive physical exercise
Myasthenic patients have an
increased incidence of several
associated disorders
 Thymic abnormalities - 75% of cases
 thymoma
 Hyperthyroidism - 3-8% of cases
 may worsen the myasthenic weakness
 other autoimmune disorders
 blood tests for rheumatoid factor, antinuclear
antibodies
Therapy

 Avoid excessive fatigue, enough sleep, avoid

stress
 Anticholinesterase medications
 Pyridostigmine (initial dose 3x60mg)
 immunosuppressive agents
 Glucocorticoids (12-50 mg prednisone, max 50-60
mg)
 Azathiopriane (50 mg/day)
 Cyclosporine (3-4 mg/kgbw/day)
 plasmapheresis
Therapy

 IVIG  0,4 g/kg/day for 5 consecutive days

especially in myasthenic crisis before
thymectomy
 Thymectomy (age <50 y.o., no remission
within 6-12 months)
Treatment for myasthenic crisis

 Airway control and ventilation

 Ach esterase
 Corticosteroid
 Plasmapharesis or IVIG
Cholinergic crisis

 Caused by Anti ch esterase medication /

excessive cholinergic drugs
 Diarhea, miosis, bronchospasm, emesis,
lacrimation, hypersalivation
Treatment for Cholinergic crisis

 Temporarily stopping anti cholin E drugs

 Airway control
 Atropin 0,4-0,6 mg i.v. every 15 minutes until
pupil dilated and brochial secreation
controlled  tapp off
 Corticosteroid
 Plasmapharesis or IVIG