Myasthenia Gravis

Myasthenia Gravis
A disease consisting of muscle weakness due to a
variable block of neuromuscular transmission in
which there is an immune-mediated decrease in the
number of functioning Acetylcholine receptors.
It is caused by a breakdown in the normal
communication between nerves and muscles.

Myasthenia Gravis

Myasthenia Gravis
Though myasthenia gravis can affect people of
any age,
it's more common in women younger than 40 and in
men older than 60.

Signs and Symptoms

double vision
Ptosis (drooping eyelids)
difficulties with speech, chewing, swallowing
weakness of arm or leg muscles
Breathing difficulties

Physical Examinations
A thorough investigation includes:

looking upward and sidewards for 30 seconds:ptosisanddiplopia

looking at the feet while lying on the back for 60 seconds
keeping the arms stretched forward for 60 seconds
ten deep knee bends
walking 30 steps on both the toes and the heels
five situps, lying down and sitting up completely
"Peek sign": after complete initial apposition of the lid margins,
they quickly (within 30 seconds) start to separate and the sclera
starts to show

Diagnostic Approach
Bedside Test:
I. IcePack Test
II. Tensilon Test
. Serologic Testing:
I. Acetylcholine receptor antibodies
II. MuSK antibodies
. Electrophysiologic confirmation:
I. Repetitive nerve stimulation
II. Single-fiber electromyography

Bedside Test:
1. IcePack Test

Bedside Test

The eyelid muscles are the most easily cooled by

the application of ice, since it is based on the
physiologic principle of improving neuromuscular
transmission at lower muscle T

Bedside Test:
2. Tensilon Test

Edrophoniumchloride is an
acetylcholinesterase
inhibitor with:
rapid onset (30 -45 secs)
short DOA (5-10 min).
This agent prolongs the presence
of acetylcholine in the
neuromuscular junction and
results in an immediate increase
in muscle strength in many of
the affected muscles.

Tensilon Test
To perform the test, a test dose of 0.1 mL of 10 mg/mL
edrophonium solution is administered.
If no response and no untoward effects are noted, remainder of the
drug (0.9 mL) is injected.
Serious complication:
Sinus bradycardia (due to excessive cholinergic stimulation of the
heart)
Antidote:
Atropine should be available at the bedside or in the clinic

Serologic testing:
Acetylcholine receptor antibodies
MuSK antibodies
Binding AChR antibodies are are highly specific for MG.
These antibodies are present in approximately 80 to 90 % of pt with
GMG.
Essentially all patients (98 to 100 %) with MG and thymoma are
seropositive for these antibodies

Other Antibodies
Antibodies to titin
Antibodies to ryanodine
Striated muscle Antibodies

Electrophysiologic Tests
Repetitive nerve
stimulation (RNS) studies
single-fiber
ElectroMyoGraphy (SFEMG)

Treatments:
Symptomatic treatments (anticholinesterase
agents)
Chronic immunomodulating treatments
(glucocorticoids & other immunosuppressive
drugs)
Rapid immunomodulating treatments
(plasmapheresis and intravenous immune
globulin)

Time to onset

Time to maximal
effect

Symptomatic therapy
Pyridostigmine

10 to 15 minutes

2 hours

Chronic immunotherapy
Prednisone

2 to 3 weeks

5 to 6 months

Azathioprine

~12 months

1 to 2 years

Mycophenolate
mofetil

6 to 12 months

1 to 2 years

Cyclosporine

~6 months

~12 months

Rapid immunotherapies
Plasmapheresis

1 to 7 days

1 to 3 weeks

Intravenous immune
globulin

1 to 2 weeks

1 to 3 weeks

1 to 10 years

1 to 10 years

Surgery
Thymectomy

Rapid Immunotherapies
The rapid therapies used in MG are also immunomodulating but are
distinct because of their quick onset, transient benefit, and their
use in select situations. Both plasmapheresis and intravenous
immune globulin (IVIG) start to work quickly (over days), but the
benefits are only short term (weeks).
These therapeutic modalities are used most often in the following
situations:
1. Myasthenic crisis
2. Preoperatively before thymectomy or other surgery
3. Periodically to maintain remission in patients with MG that is not
well controlled despite the use of chronic immunomodulating

Plasmapheresis
Plasma
exchange
directly
removes AChR antibodies from
the circulation.

Course of treatment
A typical course of treatment
consists of 5 exchanges (3-5 L of
plasma each) over 7-14 days.

Complications:
infection
and
thrombosis,
bleeding, hypotension, cardiac
arrhythmias .

Intravenous immune globulin

IVIG is pooled immunoglobulin from thousands of
donors. The effect of benefit can last for 3-6 wks.
Dose and side effectsThe total dose of IVIG is

2 g/kg, usually over two to five days.

Intravenous immune globulin

Side effects:
Headache
chills
Dizziness
fluid retention.

Other uncommon complications:

anaphylaxis.
acute renal failure
aseptic meningitis
thrombotic events

Thymectomy
Thymectomy is advocated
as soon as the patient's
degree of weakness is
sufficiently controlled to
permit surgery.
Thymectomy
is
not
routinely
suggested
in
patients over 60 years of
age, unless a thymoma is
present.

Pre-Op Managements for

Thymectomy
Acquire adequate pulmonary evaluation and
clearance to assure presence of patent airways,
optimum respiratory muscle power, adequate
clearing of secretions and absence of respiratory
infection.

The following pre-operative tests are recommended:

a) chest x-ray
b) arterial blood gases
c) pulmonary function test (including VC, FEV, MEF, flowvolume loop) and exercise testing (with 6-8 hours off
anticholinesterase inhibitor e.g. Mestinon)
d) sputum G/S, C/S when necessary

e) chest CT scan when necessary

f) perfusion studies when necessary

3. Perform cardiac evaluation as follows:

a) basic tests: ECG, chest x-ray;
b) complete cardiology evaluation and
clearance if
- the patient is 40 years old or
above
- if patient has history of ischemic
heart disease or other cardiac
problems or
risks for developing
cardiac problems.

c) 2D echocardiography when necessary

d) stress test when necessary
e) nuclear medical tests when necessary

4. Search for and adequately treat

concomitant medical conditions:
a) Infection
b) Disorders associated with MG. Do the
following tests:
- ESR
- thyroid function tests
- blood sugar
- ANA
- rheumatoid factor
c) Disturbance in nutrition, fluids and
electrolytes

5. Check CBC and bleeding parameters (CT, BT, PT, PTT).

6. Refer to Rehabilitation Medicine specialist to assure good
pulmonary capacity and adequate muscle tone.
7. Consider drug effects and drug interactions.
If the patient is on medications, ensure that there are no
side effects of these drugs or adverse drug reactions that
may interfere with or complicate the intra- and postoperative course of the patient.

What is the recommended anesthetic

management?
1. Anesthesiologists must consider the
patients disease severity including:
- voluntary and respiratory muscle
strength
- ability to protect and maintain patent
airway
post-operatively
- the type of surgical procedure and the
surgeons preferences
- patients ongoing medication (e.g.
Mestinon and
steroids).

2. For pre-operative medications:

Generally, anxiolytics, sedatives and
opioids are rarely given to patients with little
respiratory reserve.
Small dose benzodiazepines, when
necessary, may be given to patients with good
respiratory reserve.

3. Choice of anesthetic agents:

The anesthesiologist must confer with the
neurologist and the surgeon and other
specialists when needed.
There are several anesthetic agents that can
be
There is no anesthetic technique that is
superior to others. Choice depends on
preference of the doctors. These techniques
have included:

a. Avoidance of
muscle relaxants
and use of potent
inhaled
anesthetics both
for facilitating
tracheal
intubation and
providing
relaxation for
surgery.
b. Titration of small
doses of
intermediate
acting relaxants
to the evoked

d. Use of local or
regional
anesthetic
techniques.
e. The decision
whether to
reverse residual
NM blockade at
the end of surgery
or to wait for
spontaneous
recovery and
extubate when
patient
demonstrates
adequate

There is need to monitor patients especially

noting interactions of the anesthetic agents with
other drugs and keeping in mind the variable
responses the myasthenic patients may have to the
anesthetic drugs.

Omitting pyridostigmine pre-operatively may reduce

the need for muscle relaxant as well as lessen the effect
of ester anesthetic agents. However, the omission of the
pyridostigmine on the day of surgery predisposed
myasthenic patients to the possibility of respiratory
discomfort and sensitivity to vecuronium.7 (Class I
evidence)

Steroid-dependent patients have the possibility of

developing post-operative deterioration or crisis so that
they will require pre- and peri-operative coverage.8 (Level
2 evidence)
Steroids also decrease dose of non-depolarizing
relaxants to which myasthenic patients are highly
sensitive.

What is the recommended postoperative management?

6.1 Closely monitor at Post-Anesthesia

Care Unit or Surgical Intensive Care
Unit Respiratory support can be
immediately instituted
6.2 Predict as accurately as possible the
best time to extubate based on:
- Pre-operative condition of the patient
- Surgical technique used

- Residual anesthetic effect

- Parameters for weaning include: absence of
crisis
triggers, objective findings showing
adequate muscle power, vital capacity > 10 ml/kg,
negative inspiratory force > 20 cm water,
positive expiratory force > 40 cm water.

6.3 Predict as accurately as possible the need for

post-operative mechanical ventilation based on:
- Pre-operative condition of the patient
- Surgical technique used
- Residual anesthetic effect

6.4 Maintain adequate post-operative pain

control.
Avoid muscle relaxants and tranquilizing drugs.
6.5 Maintain adequate pulmonary toilet and
physical therapy
6.6 Avoid or use very cautiously drugs
interfering with neuro-muscular
transmission (Refer to Table on Drugs Acting on
NM Junction))

6.7 Determine the best time to resume

pyridostigmine/anticholinesterase and
steroids/immunesuppressants and the
appropriate dose, considering that:
- Anticholinesterases can keep muscle power at
adequate levels.
- Anticholinesterases can increase oral and tracheal
secretions.
- Steroid-dependent patients will need
immediate post-operative coverage.