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Myasthenia Gravis
Myasthenia gravis is a
disease with neuromuscular weakness of motor muscles. MG patients present in middle or
old age .Weakness of extremities, Hoarseness at the end of the day ,
drooping eye lids, difficulty in breathing and swallowing difficulty may
be present.
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Laboratory and Other Studies for Myasthenia Gravis
| Test |
Sensitivity
(%) |
Specificity
(%) |
Notes |
| Anti-AChR antibodies |
50 (ocular myasthenia
gravis), 85-90 (generalized myasthenia gravis) |
>99 |
The likelihood of positive or
negative results depends on the clinical
likelihood as well as whether the disease is
limited to muscles of the eyes or involves other
(generalized) muscles. |
| Anti-MuSK antibodies |
40 (generalized myasthenia
gravis without anti-AChR), occasional ocular
without anti-AChR |
>99 |
The likelihood of positive or
negative results depends on the clinical
likelihood as well as whether the disease is
limited to muscles of the eyes or involves other
(generalized) muscles. |
| Decremental amplitude of
compound muscle response on repetitive nerve
stimulation at 3-5 Hz/sec |
30-50 (asymptomatic muscle),
70-90 (symptomatic muscle) |
>95 |
This response is highly
dependent on many factors, including the skill
and experience of the electromyographer, whether
the rest of the study for other diseases is
normal, and whether the muscle tested is
clinically weak. In addition, certain inherited
myasthenia syndromes (nonimmune) or toxins
affecting the neuromuscular junction will have
positive test results because they have the same
neurophysiologic deficit but of different
pathogenesis and etiology . |
| Abnormal single fiber EMG |
97-98 |
50-98 |
This depends to an even
greater extent on the experience of the
electromyographer with this special technique
and elimination on clinical and neurophysiologic
grounds of certain other neurologic diseases
including other neuromuscular diseases and motor
neuron disorders (11;
25). The sensitivity of single fiber EMG
also depends on the muscle that is tested |
| Edrophonium test |
Variable |
99 |
Few, if any, other diseases
besides autoimmune myasthenia gravis or some of
the inherited myasthenic syndromes give an
unequivocally positive response or a reversible
improvement of objective weakness to incremental
iv edrophonium. However, if muscle weakness
cannot be consistently shown on exam, or is
limited to arms and legs, this test may have a
negative or equivocal result . |
| Serum TSH, free T4,
and antithyroid antibodies |
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Approximately 10% of patients
with myasthenia gravis have hyper- or
hypothyroidism at some point in their life; test
if clinically suspicious. |
| ANA, anti-dsDNA, ENA, RA
factor |
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There is an increased
incidence of rheumatoid arthritis and probably
SLE and Sjögren's in patients with myasthenia
gravis; test if clinically suspicious . |
| Serum B12 |
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There is probably an
increased incidence of pernicious anemia in
patients with myasthenia gravis; test if
clinically suspicious or if patient has
increased MCV or anemia. Follow-up tests to
confirm if B12 is low . |
| PPD skin test |
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If planning to treat patient
without recent testing with corticosteroids or
immunosuppressive therapy, test to see if
patient requires treatment with antituberculosis
therapy |
| CT or MRI of chest |
Approaches 100% for thymoma
with CT |
95% of abnormal scans have
abnormal pathology, hyperplasia, thymoma, or
cyst |
Virtually 100% of thymomas
have abnormal scans and 50% of hyperplastic
glands result in an abnormal scan. Experienced
radiologists can generally distinguish the
pattern of abnormality between thymoma and the
50% of hyperplastic glands that have abnormal
scans .
CT scans or MRI are used to assess thymic
pathology in patients with known myasthenia
gravis and have no role in the diagnosis of
myasthenia gravis |
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Consider modification of physical activity
in patients with myasthenia gravis with effort-related weakness.
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- Consider modifying the extent of different types of
physical activity including:
- Heavy physical effort
- Prolonged speaking
- Diet (soft rather than regular)
- Prolonged reading
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Background
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Perform thymectomy in patients with thymoma
and consider thymectomy in some patients without thymoma.
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- Perform CT or MRI of the chest in all postpubertal
patients with myasthenia gravis to detect thymoma.
- Recommend thymectomy in all patients with thymoma
evidence on chest CT or MRI unless extensive local spread
has already occurred.
- Consider thymectomy in select patients without thymoma
after evaluation by an experienced specialist in myasthenia.
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Drug
Treatment for Myasthenia Gravis
| Agent |
Mechanism
of Action |
Dosage |
Benefits |
Side
Effects |
Notes |
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Pyridostigmine |
ACh esterase |
30 mg-180 mg q3-q6h; 180 mg
TimeSpan® hs |
Increased strength |
Abdominal cramps, flatulence,
diarrhea, increased salivation, respiratory
secretions and sweating, bradycardia. Overdose
may produce greater weakness |
Dose adjustment requires
experience and balancing therapeutic and side
effects. Use of atropine, propantheline,
diphenoxylate plus atropine, loperamide or
glycopyrrolate may reduce muscarinic
anticholinergic side effects without blocking
the therapeutic nicotinic anticholinergic
therapeutic effect of pyridostigmine |
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Prednisone or
prednisolone |
Immunosuppression |
Varies widely 5 mg-100 mg/d
equivalent of prednisone given as daily or every
other day dose |
Improved strength |
Weight gain, cushingoid
appearance, hyperglycemia, hypertension,
osteoporosis, mood changes, psychosis, weakness,
cataracts, aseptic necrosis of hips |
Patients with myasthenia
frequently worsen with moderate or high-dose
therapy before improving |
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Azathioprine |
Immunosuppression |
2-3 mg/kg·d |
Improved strength |
Marrow suppression,
hepatotoxicity, GI distress, increased
susceptibility to infection, idiosyncratic
fever, possible oncogenesis, teratogenic |
May take 6 months to
appreciate therapeutic effect and 12-14 months
for maximal effect. Monitor CBC, LFTs. Some
physicians use the development of erythrocyte
macrocytosis as an indicator of therapeutic
effect |
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Mycophenolate mofetil |
Immunosuppression |
1.5-2 g/d in 2 divided doses |
Improved strength |
Marrow suppression, diarrhea,
increased susceptibility to infection,
teratogenic |
Similar therapeutic effects
as azathioprine but probably quicker, fewer side
effects. Monitor CBC |
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Cyclosporine |
Immunosuppression |
5 mg/kg·d |
Improved strength |
Renal toxicity, hypertension,
headaches, encephalopathy, seizures, increased
susceptibility to infection, reduced leukocyte
count |
Monitor blood levels, CBC,
BUN/creatinine levels, and blood pressure.
Progressive renal toxicity limits long-term use.
Interacts with many medications |
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Cyclophosphamide |
Immunosuppression |
100-150 mg/d po or 1 g/m2
once monthly |
Improved strength |
Hemorrhagic cystitis, marrow
suppression, increased susceptibility to
infection, teratogenic, infertility |
Used both as a daily
medication or intravenous pulse in myasthenia
gravis. Side effects limit its use to patients
with refractory disease. |
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IVIg |
Immunomodulation |
Induction with 0.4 g/kg·d x 5
days or 1 g/kg·d x 2 days; maintenance frequency
and dose vary with patient |
Improved strength |
Headache, back pain,
pruritus, hives, nausea and vomiting. Rarely
anaphylactoid reaction, serum sickness (immune
complex deposition), aseptic meningitis, renal
failure, stroke, myocardial infarction |
IVIg may or may not be as
effective as plasma exchange in chronic use.
Plasma exchange seems to be superior in time of
onset of effect in myasthenia gravis patients in
crisis. Transmission of viral infections now
seems not to be an issue, at least for any
currently known viruses |
Advise patients to reduce
physical activity when such activity increases
weakness, including bulbar or respiratory
weakness.
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- Discuss with patients and family
members:
- The need to decrease any physical
activity that increases weakness,
including bulbar or respiratory weakness
- See table Medications Producing Weakness
in Myasthenia.
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Advise patients with
myasthenia gravis to avoid medications that
increase weakness.
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- Recommend that patients:
- Avoid certain medications such as
quinine and related agents, β-blockers
and aminoglycoside, macrolide and
quinolone antibiotics.
- Contact the physician who manages
their myasthenia gravis before
initiating any medications or consenting
to any procedures
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Advise patients receiving
immunosuppressive drugs that seasonal influenza
vaccination (and vaccination for H1N1 virus)
should be considered to prevent potentially
serious infections.
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- Recommend that patients receiving
immunosuppressive drugs for myasthenia
gravis receive the seasonal influenza and
H1N1 vaccines.
- Be aware that patients on
immunosuppressive drugs should not receive
vaccines consisting of live attenuated virus
(intranasal form).
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Elements of Follow-up for Myasthenia Gravis
| Category |
Issue |
How? |
How often? |
Notes |
| History |
Response to therapy; disease
recurrence |
Ask about double vision,
ptosis, difficulty with repetitive tasks,
moving, swallowing, or shortness of breath |
At each visit, with symptoms.
Varies with how patient is doing and what
medications they are on |
Even stable patients doing
well on no immunosuppressive therapy should be
seen once or twice per year |
| History |
Adherence with and side
effects of medications |
Ask about use of medications
and side effects |
At each visit or with
symptoms, by phone or office visit at least
every 6 months |
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| Physical examination |
Response to therapy; disease
recurrence |
Look for ptosis, dysarthria,
proximal muscle weakness |
At each visit or with
symptoms, at least every 6 months if stable |
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| Laboratory |
Drug side effects |
CBC, electrolytes, BUN/creatinine,
LFTs in patients on immunosuppressive therapy |
As needed, depending on
medication and clinical status |
In patients not on certain
therapies, routine testing is seldom needed for
myasthenia gravis |
| Laboratory |
Disease recurrence |
Antibodies to AChR |
Measure initially and with
increase in symptoms |
Can be occasionally helpful
in patients on immunosuppressive therapy |
| Laboratory |
Steroid side effect |
Bone densitometry by DEXA
scan |
As needed; consider for
patients on prolonged corticosteroids |
If being treated with an
abnormal baseline follow-up, may be needed on a
yearly basis |
| Non-drug therapy |
Disease recurrence |
Plasma exchange at facility
experienced in plasma exchange for outpatient,
or inpatient for patient in crisis or rapidly
worsening |
As needed |
Treatment of myasthenic
crisis or rapid worsening, protection from
high-dose corticosteroid worsening,
prethymectomy in some patients. Side effects are
mainly due to route of vascular access and are
least with venipuncture access. Should be used
chronically only in patients refractory to other
modalities |
| Drug therapy |
Disease recurrence |
Adjust medications |
As needed, depending on
patient's clinical status |
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| Drug therapy |
Disease recurrence |
Plasma exchange |
As needed |
Should be used chronically
only in patients refractory to other modalities |
| Drug therapy |
Disease recurrence |
IVIg infusion at facility
experienced in the administration of IVIg |
As needed; patient with rapid
worsening or crisis should be in inpatient
setting |
Controversial as to whether
this is as effective as plasma exchange. Does
not seem to be as rapidly acting, so plasma
exchange preferred for crisis or rapid
worsening. Should be used chronically only in
patients refractory to other modalities |
| Patient education |
Overall management |
Remind patients to report
changes and medication side effects |
As needed, depending on
patient adherence, insight, and if there are
changes being made in therapeutic regimen |
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AChR = acetylcholine receptor; CBC = complete blood
count; DEXA = dual-energy X-ray absorptiometry; IVIg =
intravenous immunoglobulin. |
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How to contact the local chapter of
the
Myasthenia Gravis Foundation of America
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