Myasthenia

Gravis
MARK JHERVY S. VILLANUEVA, MD
Post Graduate Medical Intern
Objectives
• Define and describe Myasthenia
Gravis
• Discuss its epidemiology, etiology,
pathogenesis, clinical
manifestations, diagnosis and
treatment
• Special notes on Myasthenia Gravis
Myasthenia Gravis
• Myasthenia gravis, as the name
implies, is a muscular weakness
formerly with a grave prognosis.
Myasthenia Gravis
• A fluctuating weakness of certain
voluntary muscles
• Particularly those innervated by
motor nuclei of the brainstem
• i.e., ocular, masticatory, facial,
deglutitional, and lingual
Myasthenia Gravis
• Manifest weakening during
continued activity
• Quick restoration of power with
rest
• Dramatic improvement in strength
following the administration of
anticholinesterase drugs
Epidemiology
• Prevalence: 43 to 84 per million
persons
• Annual incidence: 1 per 300,000
• May begin at any age
• Onset in the first decade is
relatively rare
Epidemiology
• Peak Age: 20 to 30 years in
women; 50 to 60 years in men
• Under the age of 40, females are
affected 2 to 3 times as often as
males whereas in later life, the
incidence in males is higher
• Patients with thymomas: older and
males
Etiology & Pathogenesis
• The clear demonstration of an
immunologic mechanism
operative at the neuromuscular
junction has been the most
significant development in our
understanding of myasthenia
gravis.
Etiology & Pathogenesis
Normal Neuromuscular Neuromuscular Junction
Junction in Myasthenia Gravis
Etiology & Pathogenesis
Etiology & Pathogenesis
Etiology & Pathogenesis
• First in the ocular and cranial
muscles
• Fatigue: result of the normal
decline in the amount of ACh
released with each successive
impulse
Etiology & Pathogenesis
• Most patients with myasthenia have
thymic abnormalities and a salutary
response to thymectomy
• Both T and B cells from the
myasthenic thymus are particularly
responsive to the AChR
• Thymus contains “myoid” cells that
bear surface AChR
Clinical Manifestations
• Repeated or persistent activity of
a muscle group exhausts its
contractile power, leading to a
progressive paresis, and rest
restores strength, at least partially
Clinical Manifestations
• Usually the eyelids and the
muscles of the eyes, and
somewhat less often, of the face,
jaws, throat, and neck, are the
first to be affected
• Infrequently the initial complaint
is referable to the limbs
Clinical Manifestations
Clinical Manifestations
Clinical Manifestations
• Spreads insidiously from the
cranial to the limb and axial
muscles
• There are instances of fairly rapid
development, sometimes
apparently initiated by an
infection
Clinical Manifestations
Clinical Manifestations
• Muscles of facial expression,
mastication, swallowing, and
speech are affected in 80 percent
of patients
• Less frequent is early involvement
of the flexors and extensors of the
neck, muscles of the shoulder
girdle, and flexors of the hips
Clinical Manifestations
• Of the trunk muscles, the erector
spinae are the most frequently
affected
• In the most advanced cases, all
muscles are weakened
Clinical Manifestations
• Tendency to increase as the day
wears on or with repeated use of
an affected muscle group
• A fluctuating and fatigable
oculofaciobulbar palsy
Osserman Clinical Grading
MGFA Clinical Grading
1. Ocular
2. Ocular and mild systemic
weakness
3. Ocular and moderate systemic
weakness
4. Ocular and severe systemic
weakness
5. MG crisis, respiratory failure
MGFA Clinical Grading
• Subtypes*:
A. Appendicular
B. Bulbar
*Does not apply to Class 1
Diagnosis
• Complete medical and
neurological evaluation
• Patients have weakness that
comes on with activity and
improves following rest
Diagnosis
• Confirmatory Tests:
• Electrophysiologic Testing
• Single Fiber EMG
• Office Tests
• Acetylcholine Receptor Antibody
• Anti-MuSK Antibody
Electrophysiologic Testing
• A rapid reduction in the amplitude
of compound muscle action
potentials during a series of
repetitive stimulations of a
peripheral nerve at a rate of 3 per
second
Single Fiber EMG
• Demonstrates an inconstancy of
the normally invariant interval
between the firing of muscle fibers
connected to the same motor unit
or complete blocking of successive
discharges from single muscle
fibers belonging to the same motor
unit
Office Tests
• Testing with edrophonium and
neostigmine
• Edrophonium 1mg TIV, if with no
improvement, give another 4 to
9mg
• Pretreatment: Atropine 0.8mg SQ
Office Tests
• Testing with edrophonium and
neostigmine
• Edrophonium 1mg TIV, if with no
improvement, give another 4 to
9mg
• Pretreatment: Atropine 0.8mg SQ
Office Tests
• Neostigmine methylsulfate 1.5mg
IM
• Pretreatment: Atropine 0.8mg SQ
• Objective improvement occurs
within 10 to 15 min, reaches its
peak at 20 min, and lasts up to 1
hour
Anti-AchR Antibody
• Detection of anti-AChR antibodies
provides a reasonably sensitive and
highly specific test for the diagnosis
of myasthenia
• 80 to 90 percent of patients with
generalized myasthenia gravis
• 60 percent of those whose symptoms
are restricted to the ocular muscles
Anti-MuSK Antibody
• IgG antibodies directed against an
intracellular muscle-specific
kinase (MuSK)
• Enzyme responsible for supporting
the normal structure of the
postsynaptic membrane and in the
arrangement of AChR
Diagnosis
• Single fiber EMG and AChR
antibody test are primary tests
used to confirm a clinical diagnosis
of Myasthenia Gravis
Treatment
• No known cure for Myasthenia
Gravis
• Effective treatments allow many
patients with Myasthenia Gravis to
lead full lives
• Treatment goals are individualized
Treatment
• Anti-acetylcholinesterase agents
• Corticosteroids
• Immunosuppressant agents
• Plasmapheresis
• Intravenous Immunoglobulins
• Thymectomy
Anti-cholinesterase agents
Corticosteroids
• Prednisone 15 to 20 mg/day,
increasing the dose gradually until
a satisfactory clinical response is
obtained or until a daily dose of 50
to 60 mg is reached
Immunosuppressant agents
• Azathioprine 50 mg/tab BID for a
few days; if tolerated, the dosage
is raised to 2 to 3 mg/kg/day (150
to 250 mg daily)
• Other Immunosuppressants:
Cyclosporine, Mycophenolate,
Cyclophosphamide
Plasmapharesis
• Lifesaving during a myasthenic
crisis
• Several exchanges of 2 to 3.5 L
each (totaling approximately 125
mL/kg) performed over a week
• 2-L exchange will remove 80
percent of circulating antibodies in
3 to 5 days
Intravenous Immunoglobulin
• IV immunoglobulin 2 g/kg given in
divided doses over 3 to 5 days
Thymectomy
• Surgical removal of the thymus gland
• Recommended for patients younger
than 60 years with non-
thymomatous, generalized AChR
antibody-associated MG
• Preoperative plasmapheresis or IV Ig
is recommended if with respiratory
or bulbar symptoms
Special Notes on
Myasthenia
Gravis
Myasthenic vs Cholinergic
Myasthenic vs Cholinergic
LEMS vs Myasthenia Gravis
Myasthenic Syndromes
Myasthenic Syndromes
Myasthenic Syndrome of
Snake Envenomation
Myasthenic Syndrome of
Snake Envenomation
• Completely reversible muscle
paralysis
• Preserved deep tendon reflexes
with no sensory abnormalities
• Muscular weakness sets in within
an hour of envenomation and
lasted up to 10 days, with
fatigability lasting for 12 days
Myasthenic Syndrome of
Snake Envenomation
• Respiratory muscle paralysis led to
ventilatory failure
• Motor and sensory nerve
conduction were normal
• Repetitive nerve stimulation gave
rise to a decremental response
• Edrophonium test negative
Management
of
Myasthenia
Gravis
Reference
• Adams and Victor’s Principles of
Neurology, 9th ed., Myasthenia
Gravis and Related Disorders of
the Neuromuscular Junction, p.
1405
• Myasthenia Gravis Foundation of
America. http://myasthenia.org