Motor
Myasthenia Gravis
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Myasthenia Gravis
Pathophysiology
Neuromuscular
Autoimmune Disease
Antibodies form to nicotinic acetylcholine receptors
Affects post-synaptic mambrane of the neuromuscular junction
Results in fluctuating and variable, progressive weakness and true fatigability
Associated with thymoma in up to 25% of cases
Epidemiology
Annual
Incidence
: 10-20 new cases per million
Prevalence
: 150-200 cases per million
Age of onset (multimodal)
Neonatal Myasthenia Gravis (transient related to maternal antibodies)
Ages 20-30 (predominantly female)
Ages 50-80 (predominantly male)
Types
Ocular Myasthenia Gravis
Eyelid
weakness (
Ptosis
)
Extraocular
Muscle Weakness
(
Diplopia
)
Seronegative in 50% of cases
Progresses to generalized Myasthenia Gravis within 2 years in 50% of cases
Gene
ralized Myasthenia Gravis
Includes ocular
Muscle Weakness
as above AND
Bulbar weakness (
Dysarthria
,
Dysphagia
, fatigable chewing)
Extremity weakness
Respiratory
Muscle Weakness
Seronegative in 10% of cases
Other forms
Thymoma-associated Myasthenia Gravis
Associated Conditions
Neuromyelitis optica
Autoimmune
Thyroid
disease
Systemic Lupus Erythematosus
Rheumatoid Arthritis
Presentations
Early course
Typically transient with symptom free intervals lasting days to weeks
Ocular Myasthenia Gravis (50%)
Ptosis
Diplopia
(vertical or horizontal)
Bulbar symptoms (15%)
Dysarthria
Dysphagia
Fatigable chewing
Isolated motor weakness (<5%)
Proximal limb weakness
Other sites of isolated
Muscle Weakness
are less common presentations (neck weakness, distal limb weakness, respiratory
Muscle Weakness
)
Symptoms
Muscle Weakness
provoked by exertion
May be precipitated by infection, fever, stress and other acute factors
Ocular weakness
Eyelid
Muscle Weakness
resulting in
Ptosis
(unilateral or bilateral)
May increase with sustained upward gaze
Extraocular
Muscle Weakness
resulting in binocular
Diplopia
(vertical or horizontal)
Resolves with covering one eye
Pupil
reaction is always spared in ocular myasthenia
Bulbar weakness
Fatigable chewing (often mid-way through a meal)
Patient may need to use their fingers to lift the jaw, and close the mouth
Dysarthria
Nasal quality or low intensity voice
Dysphagia
Difficulty
Swallowing
liquids and solids
Aspiration may occur with myasthenia crisis
Nasal regurgitation
Occurs if
Palate
weak
Facial
Muscle Weakness
Loss of expression (especially loss of smile, or sneer appearance)
Neck
Muscle Weakness
Neck flexor
Muscle Weakness
Neck extensor
Muscle Weakness
May give "dropped head" appearance with head flexed over chest later in the day
Extremity
Muscle Weakness
(asymmetric)
Arms affected more than legs
Proximal
Muscle Weakness
are typically more affected than distal muscles
Distal wrist extensors and foot dorsiflexors are most often involved
Respiratory
Muscle Weakness
Respiratory insufficiency may progress to
Respiratory Failure
(myasthenia crisis)
Signs
See symptoms above
Muscle Weakness
as above
Deep Tendon Reflex
es normal
Specific Tests
Ice Pack Test
Cold pack applied to eye with
Ptosis
for 2 minutes
Myasthenia Gravis related
Ptosis
improves with cold applied
Tensilon Test
(
Edrophonium Test
)
Cholinesterase Inhibitor
given and
Motor Strength
improves in Myasthenia Gravis
Labs
Specific
Antibody
Seronegative Myasthenia Gravis occurs in 6-12% of cases (most frequently ocular Myasthenia Gravis)
Acetylcholine Receptor
Antibody
(AChR-Ab)
Binding AChR-Ab is typically used as it has best efficacy
Blocking AChR-Ab may be indicated in some cases due to its high
Specificity
Modulating AChR-Ab may slightly increase
Test Sensitivity
but at the risk of
False Positive
s
Present in 50% of Ocular Myasthenia Gravis
Present in 80-90% of generalized Myasthenia Gravis
Muscle-Specific Receptor
Tyrosine Kinase
Antibody
(MuSK-Ab)
Absent in most cases of ocular Myasthenia Gravis
Present in 38-50% of generalized Myasthenia Gravis patients who are AChR-Ab negative
Labs
Other testing
Electromyogram
(EMG)
Decremental response to repetitive nerve stimulation
CT neck or MRI neck
Thymoma evaluation
Thyroid Function Test
Hyperthyroidism
(3-8%)
Rheumatoid Factor
(RF)
Antinuclear Antibody
(ANA)
Differential Diagnosis
Ocular Myasthenia Gravis mimics
Hyperthyroidism
(including
Thyroid
ophthalmopathy)
Kearns-Sayre Syndrome
Brainstem
lesions
Gene
ralized Myasthenia Gravis mimics
Amyotrophic Lateral Sclerosis
(ALS)
Lambert-Eaton Syndrome
Associated with cancer, and typically affects proximal extremity
Muscle Weakness
Botulism
Neurasthenia
Intracranial Mass
lesion with extraocular affect
Drug-induced Myasthenia
Penicillamine
Polymyxin
Tetracycline
Aminoglycoside
s
Procainamide
Propranolol
Phenothiazine
Lithium
Complications
Aspiration Pneumonia
Myasthenia Crisis
Respiratory compromise
Cholinergic
crisis (excessive
Acetylcholinesterase Inhibitor
)
See
Cholinergic Toxicity
Management
Medication
Anticholinesterase
(
Cholinergic
)
Provides symptomatic relief
Most effective on extremity weakness and bulbar symptoms
Less effective on
Ptosis
Least effective on
Diplopia
Pyridostigmine Bromide
(
Mestinon
)
Child: 0.5 - 1 mg/kg every 4-6 hours up to 7 mg/kg/day
Adult: 30 mg three times daily (may be increased to maximum of 120 mg every 4 hours while awake)
Onset: 15-30 minutes
Peaks: 2 hours
Duration: 3-4 hours
Neostigmine
Less commonly used
Immunosuppressive therapy
Prednisone
Start at 20 mg qd
Increase gradually by 5 mg every 3 days to 60mg
Continue for 3 months OR
Until clinical improvement stops or declines
Taper gradually to every other day
Azathioprine
(
Imuran
)
Dosing
2 mg/kg/day
Efficacy
Effective when given with
Prednisone
Effect not seen for 6 months or more
Monitoring
Complete Blood Count
(CBC)
Liver Function Test
s (LFT)
Plasmapheresis (Plasma Exchange) and IVIg
Indicated for emergent worsening/crisis
Response rate: 70%
Management
Thymectomy
Indications
Age <60 years
Inadequately controlled on
Pyridostigmine
Thymoma discovered
Effect
Clinical improvement after thymectomy in 80%
Benefits may not be seen for 6 months
Transcervical thymectomy may be preferred
References
Calhoun (1999) Ann Surg 230:555-61 [PubMed]
Precautions
Avoid antibiotics that significantly exacerbate neuromuscular weakness
Aminoglycoside
s
Fluoroquinolone
s
Telithromycin
(
Ketek
)
Macrolide
s (
Erythromycin
,
Azithromycin
) - less effect than other agents above
Avoid miscellaneous agents that exacerbate neuromuscular weakness
Magnesium
Class Ia
Antiarrhythmic
s (e.g.
Quinidine
,
Procainamide
,
Amiodarone
)
High-dose
Corticosteroid
s
Iodinated Contrast Dye
(seen primarily with older contrast dyes)
References
Hayes in Herbert (2015) 15(9):14
References
Bird (2013) Myasthenia Gravis, in Shefner and Targoff, UpToDate, Wolters Kluwer
Keesey (2004) Muscle Nerve 29:484 [PubMed]
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