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The Evaluation of Weakness in the Electromyography Lab

Anthony Chiodo, MD, MBAUniversity of Michigan Health SystemAAPMR Meeting, San Diego

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

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

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

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

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Differential Diagnosis

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Neuromuscular Junction Disorders

Anthony Chiodo, M.D.

Motor disorder Defect affecting the relationship between

the distal motor axon and muscle Defect can be pre-synaptic, synaptic, or

post-synaptic Acquired disorders are pre- or post-

synaptic

NMJ Disorders: Nature of the Abnormality

Normal distally and conduction

Sensory Nerve Conduction Studies

Post-synaptic: Normal Pre-synaptic: inability to achieve

transmission: decreased motor evoked amplitudes but normal latency and conduction

Motor Nerve Conduction Studies

Pre-synaptic: if no motor units are seen with activation, fibrillation potentials and positive waves are possible 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

Routine Needle Examination

{Repetitive Nerve Stimulation

Physiology is Key to Understanding

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

Reserve: 300,000 quanta Mobilization: 10,000 quanta Immediate Release: 1,000 quanta

Types of Acetylcholine Stores

Mobilization store: 1500 msec Reserve: 3-4 minutes

Time Availability

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

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

Other Disorders NMJ Transmission Myotonia Neurogenic Disorders with

Denervation/Reinnervation Rapidly Progressive ALS Polyneuropathy Mononeuropathy Radiculopathy

What Other Disorders Have a Decrement To Low Frequency Repetitive Nerve Stimulation?

Yes, temperature 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?

Acetylcholine Receptor Antibodies Normal number of MEPP’s MEPP amplitude decreased by 80% Post-activation facilitation Post-activation exhaustion

Myasthenia Gravis

Increased calcium in endplate increases the quanta released

Decrement decreased, small increase in motor evoked amplitude

Post-activation Facilitation

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

SFEMG

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

Myasthenia Gravis Clinical Symptoms

I: Ocular IIA: Mild generalized IIB: Moderate generalized III: Acute severe with bulbar

symptoms IV: Late severe V: Muscle atrophy

Clinical Classifications of Myasthenia Gravis Severity: Osserman

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

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

Preventing Exacerbations in Myasthenia Gravis

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 T-cells and activate Fas ligand “guided missile”

Myasthenia Gravis Treatment

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

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

Myasthenic Syndrome

Immunogenic: responds to TPE, prednisone, and 2,4-DAP

Tumorogenic: responds to cancer therapy

Eaton-Lambert Types

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

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!