Transcript The Evaluation of Weakness in the

The Evaluation of
Weakness in the
Electromyography Lab
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Anthony Chiodo, MD, MBA
University of Michigan Health System
AAPMR Meeting, San Diego
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38 year old right handed woman comes in with
a chief complaint of weakness
Noticed it first in her inability to complete her
usual circuit training program over the last
month
Subsequently affected her aerobic exercise
program and day to day home management
activities
Case Study
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She does not think there has been any
numbness or tingling
She has not noticed it affecting one area of the
body first but is uncertain
She has had no new pain, no fever or chills, no
change in bowel or bladder control
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Past medical history is remarkable for
hypothyroidism for which she takes synthroid
Family history is significant for a maternal
grandmother with rheumatoid arthritis,
paternal grandparents with diabetes mellitus
and heart disease, father with hypertension,
mother with hypothyroidism
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Deep tendon reflexes are 1+
Pin sensation and light touch is symmetric
Strength testing shows shoulder and hip girdle
muscles in the 3-4 range, hamstrings 3, elbows
4, hands and feet 4+ to 5
There is no tenderness and no pain with ROM
Physical Examination
Differential
Diagnosis
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Neuromuscular
Junction Disorders
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Anthony Chiodo, M.D.
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Motor disorder
Defect affecting the relationship between the
distal motor axon and muscle
Defect can be pre-synaptic, synaptic, or postsynaptic
Acquired disorders are pre- or post-synaptic
NMJ Disorders: Nature of
the Abnormality
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Normal distally and conduction
Sensory Nerve Conduction
Studies
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Post-synaptic: Normal
Pre-synaptic: inability to achieve transmission:
decreased motor evoked amplitudes but
normal latency and conduction
Motor Nerve Conduction
Studies
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Pre-synaptic: if no motor units are seen
with activation, fibrillation potentials and
positive waves are possible
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Botulism
Otherwise, decreased amplitude motor units
of varying amplitude and rapid recruitment
Post-synaptic: varying amplitude motor
units with rapid recruitment
 If myasthenia gravis: may see proximal
fibrillation potentials and positive waves
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Routine Needle Examination
Physiology is Key
to Understanding
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Repetitive Nerve
Stimulation
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Molecules = Quanta X # Released(p)
Typical Quanta = several thousand
acetylcholine molecules, generate MEPP,
amplitude 1 mV
P typically around 60 quanta released per nerve
stimulus
Muscle action potentials at 7-20 mV
Presynaptic Acetylcholine
Stores
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Reserve: 300,000 quanta
Mobilization: 10,000 quanta
Immediate Release: 1,000 quanta
Types of Acetylcholine Stores
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Mobilization store: 1500 msec
Reserve: 3-4 minutes
Time Availability
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Decreased quanta released per nerve
stimulation
Synaptic vesicle fusion time(Ca++ dependent) is
100-200 msec
Maximal decrement at 2-3 Hz
No decrement at 10 Hz
Normal decrement < 8%
Concept of Decrement
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1st stimulus: 60 quanta
2nd stimulus: 56 quanta
3rd stimulus: 53 quanta
4th stimulus: 55 quanta as reserve quanta
become available
Accounts for decrease in EPP and results in
increase risk of failure (blocking) over four
repetitive stimulations at 2 Hz
At 2 Hz Repetitive
Stimulation
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Other Disorders NMJ Transmission
Myotonia
Neurogenic Disorders with
Denervation/Reinnervation
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Rapidly Progressive ALS
Polyneuropathy
Mononeuropathy
Radiculopathy
What Other Disorders Have a
Decrement To Low Frequency Repetitive
Nerve Stimulation?
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Yes, temperature
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Increased decrement and blocking at increased
temperature due to increased
acetylcholinesterase activity
May account for the fact that the effect is more
pronounced in proximal muscles
Are there any physiological
parameters that effect this
finding?
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Acetylcholine Receptor Antibodies
Normal number of MEPP’s
MEPP amplitude decreased by 80%
Post-activation facilitation
Post-activation exhaustion
Myasthenia Gravis
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Increased calcium in endplate increases the
quanta released
Decrement decreased, small increase in motor
evoked amplitude
Post-activation Facilitation
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Depletion of mobilization and immediate
release stores, before reserve store becomes
available
Decreased receptor excitability
Characteristic of Myasthenia Gravis
Post-activation Exhaustion
Recording surface 25 mcm to pick up
from single muscle fiber
 Quantify the differences in time of
onset of firing of two muscle fibers
from the same motor unit
 Jitter is the mean difference in this
firing onset time
 Blocking is the rate of failure of a
muscle fiber from firing with it’s
motor unit
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SFEMG
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Pre- and post- synaptic neuromuscular junction
disorders
Ongoing neuropathic processes: motor neuron
disease, neuropathy, radiculopathy
Diagnoses with Increased
Jitter
Hallmark: Fluctuating weakness
 Diplopia
 Ophthalmoplegia
 Ptosis
 Facial Weakness
 Dysphagia
 Vocal cord weakness
 Respiratory muscle weakness
 Pelvic floor muscle weakness
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Myasthenia Gravis Clinical
Symptoms
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I:
IIA:
IIB:
III:
IV:
V:
Ocular
Mild generalized
Moderate generalized
Acute severe with bulbar
symptoms
Late severe
Muscle atrophy
Clinical Classifications of
Myasthenia Gravis Severity:
Osserman
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Active:
5-7 years
Inactive:
10 years
Burned Out: Slow improvement seen
40-50% of ocular myasthenics will become
generalized in the first 2 years
Clinical Course in Myasthenia
Gravis
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Antibodies: 80% generalized, 55% ocular
Seronegative: 70% with anti-MuSK Ig
Rep Stim: 76% generalized, 48% ocular
Limb SFEMG: 89% generalized, 60% ocular
Facial SFEMG: 92% ocular
Myasthenia Gravis Diagnosis
Evaluate/treat other autoimmune
disorders: RA, thyroid, B-12
 Pacing
 High K+ diet
 Avoid excessive heat>cold
 Watch for cyclic changes in women
 Avoid botox, quinamm,
aminoglycosides, tetracyclines,
anesthetic agents, anticonvulsants
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Preventing Exacerbations in
Myasthenia Gravis
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Mestinon: Acetylcholinesterase inhibitor
Prednisone
Imuran, Cytoxan, Cyclosporine, Mycophenolate
Therapeutic Plasma Exchange
Thymectomy
AchR-based Immunoadsorbants
Mucosal injection of AchR-recombinant
fragments
IG to proinflammatory cytokine IL-18 and
costimulatory factor CD40L
Create viral manipulated antigen presenting cells
that express AchR to present to AchR-specific Tcells and activate Fas ligand “guided missile”
Myasthenia Gravis Treatment
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Creatine plus resistance exercise with normal
treatment in mild MG shows improved
strength and muscle mass
Isometric exercise effective in improving
strength in mild MG
Exercise in Myasthenia
Gravis
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Increased acetylcholinesterase activity
Decreased sensitivity of acetylcholine receptors
More rapid presynaptic acetylcholine depletion
Can explain proximal>distal weakness
Effect of Temperature in
Myasthenia Gravis
Antibodies prevent pre-synaptic Ca++
influx prevents quanta release
 Decreased number of MEPP’s of
normal amplitude
 Decrement to low frequency rep stim
due to many muscle fibers activated
near-threshold so decreased release is
miniscule but significant
 Post-exercise facilitation due to
increased Ca++ in cell resulting in
increased quanta release with next
nerve stimulus
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Myasthenic Syndrome
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Immunogenic: responds to TPE, prednisone,
and 2,4-DAP
Tumorogenic: responds to cancer therapy
Eaton-Lambert Types
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Food, wound or infantile
Markedly decreased pre-synaptic release due to
botulinum toxin binding to and entry into the
nerve terminus membrane
Cleave proteins in synaptic vesicle membrane
inhibiting release
Complete binding may result in no increment
to exercise
Complete binding may lead to fibrillation
potentials and positive waves
Botulism
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LEMS: hallmark is marked incremental
response with exercise
AIDP
Critical illness myopathy
Botulism Differential
Diagnosis
Does not include neonatal myasthenia gravis
 Presynaptic: failed production, storage and
mobilization of acetylcholine
 Acetylcholine receptors: decreased number,
decreased binding, prolonged binding/opening
 Congenital absence of acetycholinesterase
Congenital Myasthenia
Gravis
Thank you!