DIAGNOSIS AND MANAGEMENT OF MYASTHENIA GRAVIS

By : Desya Billa Kusuma Anindhira

Lecturer Adviser:
dr. Donny H Hamid Sp.S
 Definition
Myasthenia Gravis (MG) is a chronic autoimmune disease which characterized with fluctuate
weakness and fatigue of the extrinsic ocular muscles. The symptoms usually progress to the other
bulbar muscles and limb muscles, resulting in generalized MG. The muscle weakness will worsen
with activities and improve with rest. Myasthenia Gravis is caused by the presence of autoantibody
at the post synapse membranes in the neuromuscular-junction.
Epidemiology
Incidence: > 50 man predominate with
1.7 to 21.3 per 1000.000 3:2

woman predominate Highest Women in age 20-30,

< 50
with 7:3 prevalence while men in age 60
Anatomy and Physiology of the Neuromuscular Junction
 Ethiopathogenesis
The autoantibodies fix onto Ach
acetylcholine receptors sites, blocking the binding of
receptors acetylcholine.
(AChR)

muscle-specific MuSK protein plays a critical role in

Pathogenesis Of MG tyrosine kinase autoregulating the concentration of the
(MuSK) AChR on post-synaptic membrane

(rare case)
Low-density LRP4 is essential for maintaining the
lipoprotein receptor- structural and functional integrity of the
related protein 4 neuromuscular junction
(LRP4)
NORMAL Myasthenia Gravis
“
Ten percent of patients with myasthenia gravis have a thymic tumor
and 70% have hyperplastic changes (germinal centers) that indicate an

”
active immune response

lymphoid
tissue myoid cells

AChR antigen,
B-cells interact with
antigen presenting
helper T-cells
cells, and
producing antibodies
immunocompetent
T-cells
Clinical Presentation

✢
Ocular symptoms

Ptosis Diplopia

1. Ocular symptoms
2. Bulbar Symptoms

DYSARTHRIA

DYSPHAGIA

“EXPRESSIONLESS”
appearance

“SNARLING”
appearance
3. Neck and limbs
Neck
• Neck flexor and extensor muscles are often weak in MG.
• Though the neck flexors are usually weaker

Neck Extension
weakness

"dropped head
syndrome" Posterior neck
myalgias
Limbs

Finger and wrist extensors and shoulder

UPPER LIMBS
abductor muscles are most likely to be affected

the foot dorsiflexors and hip flexors are most

LOWER LIMBS
frequently involved
Respiratory
• tachypnea and shallow breathing
• an inability draw a full breath
Ask patient
to:
inspiratory expiratory

Inspire forcefully Cough or clear

and loudly
their throat
through nose
A weak sniff and cough along with significant tachypnea or tachycardia are signs of
clinically important respiratory muscle weakness.
Clinical Classification
Diagnosis of Myasthenia Gravis

case history

Physical
examination
Myasthenia
Gravis
Electrodiagnostic
testing

Laboratory Tests
Case History

Patient came with patient history:

suspicion of MG • patient manifests symptoms of ptosis, diplopia,
and/or blur, which increases with use of the
ocular muscles, or as the day progresses.
• Patients with generalized MG may also manifest
fatigue of the face, neck, and limbs, worsening
with activity.
• Head droop and down-sloping of a smile may be
noted
 Physical Examination

Ocular Myasthenia
✢ Patients may have diplopia at rest or it
may only come out with use of the
eyes
✢ Repeating eye movement : sustained
upgaze or repeated blinking
will exacerbate any weakness and
bring out diplopia and ptosis
Limb weakness
Ask patient to:
lift their arms to 90 degrees and If equal
move ONE ARM up and
check their shoulder abduction
down 20 times
and adduction

fatigue

retest shoulder abduction and

adduction and compare sides

Both abduction and adduction should now be

demonstrably weaker than in the unused arm
 Central/bulbar involvement
o Test the power of head/neck flexion and
extension (fatigue this movement)
o Ask the patient to take a deep breath and count
out loud as many numbers as they can. Compare
this to your own (i.e. count at the same time)
 Ice Pack Test
• An ice cube is placed over the drooping eyelid for about two minutes
• if there is improvement in the ptosis, it suggests a neuro muscular
transmission disorder
 Tensilon test
• Edrophonium chloride temporarily improves strength in patients with abnormal
neuromuscular transmission

During testing, up to 10 mg of intravenous edrophonium chloride

administered

+ the elevation of eyelids in 2-5 minutes

post adminstration of Tensilon
- A negative response is no
improvement within 3 minutes
Before Tensilon Test After Tensilon Test
Imaging
All MG patients should have computed tomography (CT) or magnetic
resonance imaging (MRI) of the thorax to screen for thymoma or thymic
hyperplasia. Imaging of the mediastinum should be repeated in the
context of a MG relapse after a period of stable disease to exclude the
development of a thymoma, which can occur later in the disease course

✢
 Electrodiagnostic testing

Repetitive Nerve Stimulation

Single-Fiber
Electromyography (SFEMG)
Repetitive Nerve Stimulation
• In MG repetitive closely timed stimuli will often produce progressively smaller or
weaker responses in the muscle recording electrodes
• This is called Decrement of the Compound Muscle Action Potential (CMAP)
 Single-Fiber
Electromyography (SFEMG)
• This test use a selective recording technique in which a specially
needle is used to identify and record action potentials.
• Jitter can be thought of as a measure of the fatigability within a
microscopic single motor unit
Laboratory Tests
Antibodies

• The presence of serum binding antibodies to human AChR is highly specific

for the diagnosis of MG

• In 74% of patients with myasthenia gravis, serum antibodies to acetylcholine

receptor are present.

• Virtually all MG patients with thymoma will have elevated AChR binding
antibodies
Treatment
Cholinesterase inhibitors

Pyridostigmine bromide
Initial doses of 30 to 60mg of pyridostigmine every 3 to 6 hours
Corticosteroids
Prednisone
• A dose of 60 to 80 mg daily is usually recommended
• acute worsening of weakness may be observed in first 7 to 14 days after treatment
• start with a lower dose and gradually titrate up

Non-steroidal immune suppressants

Azathioprine
• is usually provided at a dose of 2 to 3 mg/kg divided into two or three doses per day
• A treatment response takes over 12 months usually.
• alternative immunosuppressants are methotrexate (second line), mycophenolate mofetil or
tacrolimus
Rapid short-term immunomodulation
• Intravenous immunoglobulin (IVIG) or plasma exchange (PE) is used in
acute severe exacerbations of generalised MG or to optimise muscle
strength prior to surgery.
• IVIG and PE are equal first-line treatments because they have similar
efficacy

Long-term immunomodulation
• Thymectomy within the first three years of diagnosis may lead to a better
response.
• The procedure is commonly restricted to patients under the age of 60-65
years
• Anti-MuSK antibody-positive patients tend to have a poorer response
Emergency Aspect of
Myasthenia Gravis

Myasthenic Cholinergic
crisis Crisis
Myasthenic crisis
Myasthenic crisis is a complication of myasthenia gravis
characterized by worsening of muscle weakness,
resulting in respiratory failure that requires intubation and
mechanical ventilation
Respiratory Management of
Myasthenic Crisis
✢ Two-thirds to 90% of patients with myasthenic crisis require
intubation and mechanical ventilation
✢ Once intubated, patients should be placed on an assisted
ventilator setting with tidal volumes of 8-10 cc/kg ideal body
weight and pressure support of 8-15 cm H2O to prevent
atelectasis and to minimize the work of breathing
✢ Noninvasive ventilation (NIV) may be used to prevent intubation
or reintubation of patients in myasthenic crisis.
✢ With bilevel positive airway pressure (BiPAP), positive pressure
is applied during both phases of respiration, enhancing airflow
and alleviating the work of breathing during inspiration and
preventing airway collapse and atelectasis during expiration
 Cholinergic crisis

✢ myasthenia gravis-> is the use of acetylcholinesterase inhibitors

(AChEI) such as pyridostigmine
✢ AChEI prevents the breakdown of ACh by inactivating AChE
✢ This stops the breakdown of ACh and increases its level and duration
of action at the postsynaptic membrane
✢ Excessive use of AChEI in the treatment of a patient with MG may
precipitate a cholinergic crisis which is characterized by both
muscarinic and nicotinic toxicity
 Clinical Findings Related to Stimulation
of Muscarinic Receptors
S- Salivation ✢ D- Diaphoresis and Diarrhea
L- Lacrimation ✢ U -Urinary frequency
U -Urinary frequency ✢ M-Miosis
D-Diarrhea ✢ B-Bronchospasm and
G- Gastrointestinal cramping Bronchorrhea
and pain ✢ E – Emesis
E- Emesis ✢ L – Lacrimation
M- Miosis ✢ S – Salivation
✢ Clinical Findings Related to Stimulation of Nicotinic Receptors
✢ Muscular weakness
✢ Muscular fatigue and fasciculation
✢ Respiratory muscle weakness
✢ Tachycardia
✢ Hypertension
✢ Clinical Findings Related to Stimulation of the Central Nervous System
✢ Seizures
✢ Coma
✢ Ataxia
✢ Slurred speech
✢ Agitation and restlessness
In the history taking, it is very pertinent to determine
the cause of the cholinergic crises:
✢ Medications for the treatment of myasthenia
gravis or glaucoma, including pyridostigmine
✢ Ingestion or exposure to insecticides,
pesticides, or herbicides
✢ Exposure to nerve gas

✢ Reversal of neuromuscular blockage

Cholinergic Crisis
Emergency Room Management
✢ Regardless of the etiology of cholinergic crises, the core principle in
stabilization is ABC: Airway, Breathing, and Circulation.
Inpatient Management
✢ Inpatient care includes continued cardiopulmonary support and
monitoring. Patients with cholinergic crisis should be admitted to the
intensive care unit.
Antidotes for cholinergic crisis
✢ Two types of antidotes are used for a cholinergic crisis: atropine
and oximes.
THANK YOU
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