Transcript Myasthenia Gravis

Myasthenia Gravis
Victor Politi,M.D.
Medical Director, SVCMC
School of Allied Health,
Physician Assistant Program
Pathophysiology
 The
underlying defect is a decrease
in the number of available Ach
receptors at neuromuscular junctions
due to an antibody mediated
autoimmune attack
Pathophysiology
 Pathophysiology
• ACh synthesized in the motor nerve
terminal and stored in vesicles
• ACh released causes miniature end plate
potentials
• Action potential release ACh and
combined with postsynaptic receptors
• Postsynaptic channels are open allowing
entry of sodium producing depolarization
of muscle fiber
Pathophysiology
A
process is terminated by hydrolysis
of ACh by AChE
 The fundamental defect is a decrease
in the number of ACh receptors at
the postsynaptic muscle membrane,
therefore, although ACh is released
normally it produces small end plate
potentials which fail to trigger muscle
action potentials
MG- Autoantibodies protect against the
postsynaptic acetylcholine receptors
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
Myasthenia gravis (MG)
 Neuromuscular
disorder
characterized by weakness and
fatigability of skeletal muscles
 There is no cure for MG but
treatment is highly effective
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
Clinical Features
 Weakness
typically increases during
repeated use (fatigue) and may
improve during rest or sleep
 Course of MG - variable
 Remissions - rarely complete or
permanent
Clinical Features
 Unrelated
infections or systemic
disorders may lead to increased
myasthenic weakness and may
precipitate a “crisis”
 A crisis is if weakness in respiration
or swallowing becomes severe and
respiratory assistance or intubation
is necessary
Clinical Features
 Characteristic
pattern of muscle
weakness
 early involvement -lids and
extraocular muscles
 diplopia and ptosis common initial
complaints
 Difficulty in swallowing may occur
Clinical Features
 In
85% of cases, weakness becomes
generalized, affecting limb muscles as
well
 Limb weakness is often proximal and
may be asymmetric
 deep tendon reflexes are preserved
Diagnosis and Evaluation
 Suspect
on basis of weakness and
fatigability as previously described
 No loss of reflexes or impairment of
sensation or other neurologic function
 Edrophonium- initial dose 2mg IV,
second dose 8mg IV
 ACh receptor antibody detectable in
80% of all myosthenic patients
Differential Diagnosis
 Several
other conditions that cause
weakness or the cranial and/or
somatic musculature must be
considered in the differential
diagnosis of MG:
• drug induced myasthenia, Lambert-Eaton
myasthenic syndrome,neurasthenia
• hyperthyroidism, botulism, intracranial
mass lesions and progressive external
ophthalmoplegia
Differential Diagnosis
 Drugs
that may exacerbate MG
• penicillamine
• aminoglycoside antibiotics
• procainamide
Lambert-Eaton myasthenic
syndrome
 Presynaptic
disorder of
neuromuscular junction - causes
muscle weakness similar to MG
 proximal muscles of lower limbs most
commonly affected
 ptosis of the eyelids and diplopia in up
to 70% of patients
LES- Autoantibodies against the presynaptic
voltage-gated calcium channels
Lambert-Eaton myasthenic
syndrome
 MG
and Lambert-Eaton myasthenic
syndrome are readily distinguished
 patients with Lambert-Eaton
syndrome have depressed or absent
reflexes, autonomic changes (dry
mouth, impotence) and show
incremental responses on repetitive
nerve stimulation
Lambert-Eaton myasthenic
syndrome
 LES
is caused by auto antibody
directed against calcium channels on
the motor nerve terminals resulting in
impaired release of ACh
Lambert-Eaton myasthenic
syndrome
 Majority
of patients with this
syndrome have an associated
malignancy - most commonly small cell
carcinoma of the lung
 The diagnosis of Lambert-Eaton may
signal the presence of the tumor long
before it would otherwise be
detected
Lambert-Eaton myasthenic
syndrome
 Treatment
involves plasmapheresis
and immunosuppression, as for MG
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
Thymoma on CT of chest
 Chronic
infection of any kind can
exacerbate MG
 measurements
of ventilatory function
are valuable because of the frequency
and seriousness of respiratory
impairment in myasthenic patients
 Because
of the side effects of
glucocorticoids and other
immunosuppressive agents used in the
treatment of MG, a through medical
history/exam should be made
 Particular
attention should be paid to
evidence of chronic or latent infection
(tuberculosis/hepatitis), HTN,
diabetes, renal impairment, and
glaucoma
Therapy
 The
prognosis has improved greatly
for MG cases due to advances in
treatment
 virtually all MG patients can be
returned to productive lives with
proper therapy
Therapy
 Anticholinesterase
medications
• pyridostigmine
 immunosuppressive
agents
• glucocorticoids, azathiopriane
 thymectomy
 plasmapheresis
Management of myasthenic
crisis
 Exacerbation
of weakness sufficient
to endanger life
• respiratory failure
• aspiration
 The
possibility that the deterioration
should be due to excessive anti -ChE
medication (cholinergic crisis) is best
excluded by temporarily stopping
anti-ChE drugs
Management of myasthenic
crisis
 The
most common cause of crisis is
intercurrent infection
 The myasthenic patient with fever and
early infection should be treated like
other immunocompromised patients
with early antibiotic therapy,
respiratory assistance, and pulmonary
physiotherapy. Plasmapheresis is
frequently helpful in hastening recovery
Questions ??