Transcript Medical and Surgical Management of MG

Medical and Surgical
Management of MG
Brian A. Crum, MD
Department of Neurology
Mayo Clinic
Rochester, MN
MGFA National Meeting, St. Louis
May, 2010
Basic Facts
 Prevalence
20 in 100,000
 Women: younger (30’s); Men: older (40’s)
 The disease looks different in different
people
 The disease is treatable
 Most patients improve and do well
 The disease is most active the first few
years
 There are significant costs, side effects,
and manifestations of the disease
Variables in Treatment
 Ocular
vs. Generalized vs. Crisis
 Types of antibodies (AchR vs. MuSK)
 Thymoma or not
 Age and other medical conditions
 Men vs Women (esp childbearing)
 Access to healthcare
 Not:
Levels of antibodies in the blood
Ocular vs.
Generalized
 Ocular:
Just in the eyes
 Generalized: Face, arms, legs, neck
 80+%
of MG starts in the eyes
 Many will ‘generalize’ in the first monthsyear
 Most that DON’T generalize at a year will
remain ocular
Ocular vs. Generalized
 Treatment
is mostly symptomatic
 If double vision and droopy eyes are a
problem, need treatment
 Treatment
with steroids may reduce the
chance of ‘generalizing’
 Thymectomy generally not recommended
for just ocular disease
Types of Antibodies
 MuSK






antibody positive MG
Affects face, neck, shoulders, breathing
Tests (like EMG) may not show as much of
the MG changes
AchR antibodies are negative
Mestinon/pyridostigmine less effective, may
make weakness worse
Plasma Exchange works
Thymectomy probably not
Thymoma or Not
 10-20%
of MG patients have a thymoma
 Most have no symptoms (other than MG)
 Found with imaging like CT
 Surgery is done to remove tumor


Usually totally removed
If not, chemo or radiation done w/ oncologist
 MG
is more difficult to treat
Overview--Treatments

Short Term

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
Medium Term

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Immune-Mediating: Several
Longer Term


Immune-Mediating: Steroids
Long Term


Symptomatic: Mestinon
Immune-mediating: IVIG, Plasma Exchange
Thymectomy
Goal: Normalize strength, minimal medications
(or none)
Mestinon (pyridostigmine)
 Short-acting

30-60 minutes to start working, lasts a few
hours
 Used
‘as needed’
 Patients can experiment with doses


½ to 1 to 2 pills at a time
3-6 times a day
 Too
much can lead to cramps, twitching,
diarrhea, sweating, more weakness
 Also a longer-acting form (at night)
NeuroMuscular
Transmission
Acetylcholine
Ach Esterase
Ach
receptor
Muscle Contraction
Short-Term: IVIG/Plasma
Exchange
 Usually
for severe weakness (ie in the
hospital)
 One not better than the other (in studies
on crisis)
 IVIG shown to be effective in improving
weakness and reducing need for steroids
in outpatients with MG
IVIG
 3-5
days in a row
 Pooled antibodies from blood donors

Screened for transmissible disease
 Thought
to reduce the immune attack on
muscle
 Improvement w/in days
 Requires and IV in the arm
 Expensive, but typically covered
 Done more in outpatient setting now
Plasma Exchange
 “Filtering”
of blood through a
machine
 Typically done every other day for 5-7
exchanges (10-14 days)
 May required a larger IV line (central line)
placed in neck or chest

Risks of infection or blood clotting
 Improvement
in days
 Usually reserved for hospital patients
Medium-Term
 Prednisone
(the ‘love/hate’ drug)
 Proven to work in MG
 Takes days to weeks to see improvement
 Usually given as pills, sometimes IV
 Doses and frequency (every day or every
other day) vary
 Initial high doses can lead to more
weakness
Prednisone
 Inexpensive
drug
Side Effects many:
-Weight gain, puffiness
-Facial hair
-Bone thinning*
-Stomach irritation*
-Infections*
-Diabetes, high blood pressure, glaucoma
*=other medications can be given for these
Steroid-Sparing Drugs
“Long-Term”
 General
idea is to use these to allow
reduction and elimination of Prednisone
 Or, sometimes to avoid using it altogether
 Require monitoring of lab tests

Blood counts, liver tests
Steroid-Sparing Drugs
“Long-Term”
 Imuran


(azathioprine)
Most commonly used
Takes 6-12 months to ‘work’
 Cellcept


(mycophenolate)
Studies have shown it may not ‘work’
Takes months to ‘work’ (> 6)
 Cyclosporin

or Tacrolimus (FK506)
Studies show these ‘work’
Steroid-Sparing Drugs
“Long-Term”
 Others:
 Cyclophosphamide
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
Given by mouth or IV
Reserved for severe disease
 Rituximab


(Cytoxan)
(Rituxan)
Given IV weekly for 4 weeks
Reserved for severe disease
Longer-Term
Thymectomy
 Done
since the 1930’s/1940’s
 Not proven definitively to help
 Data:

1.5 to 2 times higher chance that a patient will
have remission after thymectomy
 But:


Studies are not controlled or randomized
Other factors go into how patients do (for
example who gets picked to have surgery)
Longer-Term
Thymectomy
 International

MGTX study ongoing
Patients randomized to getting surgery or not
 Also
controversial what kind of thymectomy
to do

More minimal invasive surgery
 Considered
in patients with generalized
disease, within the first few (2-3) years and
all patients with thymoma
 Doing
well
 Some disease
 Crises
 In
relation to common medical conditions
 In relation to common surgical conditions
Newly Diagnosed-Clinic
 Mestinon
 If
not fixing weakness, then…
 Prednisone
 IVIG
 Eventual taper of prednisone with or
without a steroid-sparing drug
 Get disease stabilized
 Consider thymectomy
Newly Diagnosed-Hospital
 Plasma
Exchange or IVIG
 Prednisone
 +/- Mestinon
 Imaging of chest to look for thymoma


If none, thymectomy can be considered, but
once patient is stabilized (may be months)
If yes, then operate when safe medically
Doing fine, maintenance
 Mestinon
 Tapering
Prednisone
 +/- a steroid-sparing drug
 Question
becomes when to stop the
steroid-sparing drug if patient is in
remission
Exacerbations
 Treat
any medical factor that may
contribute
 Start or increase Prednisone
 Use IVIG for a course of 3-5 days

Sometimes weekly or monthly
Difficult to control disease
 Regular
IVIG or plasma exchange
 A different steroid-sparing drug
 Thymectomy (if not done)
Medications that affect MG
 Antibiotics

Cipro, Gentamicin, Levaquin, Erythromycin,
Azithromycin (aka Z-pak)
 Bo-Tox
 Less


likely:
Blood pressure drugs
Statin medications
Other symptoms in MG
 Fatigue,


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fatigue, fatigue
Adequate sleep
Treatment of pain
Treatment of depression
Review medications
Regular exercise
Thanks!!
 MG
is diagnosable
 MG is treatable
 Treatment is individualized, but effective in
most
 We need better treatments and answers to
treatment questions (like thymectomy)