Dr. /June CMT-MDA chat transcript

[Guest guest]

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Wed., June 25, 2003

Muscular Dystrophy Association (MDA)

MDA CLINICAL-RESEARCH CHAT " CHARCOT-MARIE-TOOTH-DISEASE (CMT) "

Guest Host: , M.D.

Dr. is an MDA Clinic Director and Professor of Clinical Neurology

and Clinical Professor of Pathology, Neuromuscular Disorders,

Neuroscience Program, Tulane University, New Orleans, Louisiana. His

specialties include clinical and molecular genetic aspects of

Charcot-Marie-Tooth, muscular dystrophies and familial spastic

paraparesis, and neuropathology with emphasis in the pathology of muscle

and nerve. Dr. has contributed significantly to the MDA

Ask-the-Experts feature.

MDA Host: Dan Stimson, Ph.D., Senior Science Writer

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QUESTION -- My doctor said that it looks as if the nerves in my legs are

trying to regenerate. I was just wondering if they can stop and get

worse or if they will keep getting better? Is there anything I could do

to help the muscles in my legs from continuing to atrophy, for example,

jumping on the trampoline?

DR. GARCIA -- In CMT1, the demyelinating type, the nerves try to

regenerate but are unable to do so, and instead the Schwann cells

multiply around the axon producing an enlarged (hypertrophic) nerve. You

need to use physical therapy (PT) to keep the muscles active.

QUESTION -- I am a 44-year-old female who might have CMT. I had a nerve

conduction (NC) study two years ago. It was negative, but if I have it

done again will I benefit from it?

DR. GARCIA -- Nerve conduction studies are a test not a treatment. In

CMT1 the NC velocities stay the same from childhood.

QUESTION -- I have CMT (56 years/female) and back pain directly related

to prolonged walking. Topamax for nerve pain helps greatly. Can you

recommend any way of dealing with this back pain?

DR. GARCIA -- Back pain is produced by many causes. AFO braces help to

relieve the strain put on the spine by the weak leg muscle and

frequently help the back pain. The pain may not be related to CMT, and

you need to have imaging studies of your lumbar spine to rule out disc

disease, osteoarthritis, etc. Anti-inflammatory medicines are good for

arthritic back pain. There are other causes of back pain in CMT. You

need to see a specialist in the field.

QUESTION -- I have been doing stretches every night independently, but

as I get older I have more trouble with shaking hands. Is there

something I can do to minimize the shaking?

DR. GARCIA -- Shaking and tremors are frequent in CMT and are produced

by weak muscles. Coffee, alcohol, stress and cigarettes make the tremors

worse and should be avoided.

COMMENT -- I don't use any of those substances. What else might help me?

DR. GARCIA -- Essential (familiar) tremor may be a co-inherited factor

in CMT that can be controlled with medications. Medical treatments for

tremors include beta blockers (Inderal), Primidone, Topamax, Klonopin

(anticonvulsants), etc. - all of these are prescription medications. You

need to consult a neurologist about the one most appropriate for you.

QUESTION -- Are CMT and muscular dystrophy (MD) genetically related?

DR. GARCIA -- " MD " is generally considered a group of neuromuscular

disorders (NMDs) that include different genetic disorders. In CMT there

are at least 18 different genes that have been found.

DR. STIMSON -- Defects in a gene called LMN-A can cause either CMT or

MD, and to that extent, the diseases are genetically related. But don't

worry - that doesn't mean that people with CMT will develop MD, or vice

versa.

QUESTION -- I am 55 and was diagnosed in my early teens with CMT - I

don't know the type. I went to the local MDA clinic for the first time

about three years ago. The doctor used a machine with electrodes

attached to my hand - nerve conduction test. After increasing the

voltage several times, she said it didn't show anything. Does this

result point to any of the types more than the others?

DR. GARCIA -- It is difficult to know what she meant. There are two

possibilities. One is that she could not get a response to the nerve

stimulation and had to increase the voltage too high and still have no

response. In that case you may have a severe form of demyelinating

neuropathy. On the other hand she may be telling you that the test was

normal, and in that case you may have CMT2. Normal nerve conduction

studies are seen in the CMT2, the neuronal (axonal) type.

QUESTION -- Can CMT have any effect on the autonomic nerves that control

urinary and gastrointestinal functions? How about other autonomic

problems: fluctuating blood pressure and heart rate, inappropriate sinus

tachycardia and postural orthostatic tachycardia?

DR. GARCIA -- I don't remember of any type of CMT affecting the

autonomic nervous system (ANS). CIDP and other acquired neuropathies

affect the ANS.

QUESTION -- My daughter, age 9, has just been diagnosed with CMT. At

present she has some insensitivity in the lower legs and arms, cannot

put her heels down to walk and demonstrates some weakness in her lower

arms and legs. Since no one in our extended families shows any symptoms

of the disease, it is thought that it is probably the autosomal

recessive version. Will the particular type of CMT that she has indicate

a

rate of progress for the disease? CMT4 seems one of the most aggressive

forms. Can CMT4 develop at this age or only from birth? Given her

present status, is there a way to predict the rate of progression with

the disease? Does the disease tend to degrade in a linear manner or are

there periods of rapid decline and then periods of slow decline?

DR. GARCIA -- The clinical description of your daughter suggests an

early and severe form of the disease. Lack of family history suggests an

autosomal recessive type of inheritance, a new mutation case, or that

other affected family members show a very mild form of the disease

(clinical variability), etc. She needs to get a DNA test to find out

exactly what type she has to have a better idea of the prognosis. The

rates of progression of all forms are quite variable. However, all types

of CMT progress slowly but relentlessly.

DR. STIMSON -- I believe CMT4 is most common among people of Middle

Eastern descent and tends to have its onset at birth.

QUESTION -- I live in Egypt. Where do you recommend I go for DNA tests?

DR. GARCIA -- I am not sure where to get the DNA studies in Egypt. I

know of labs in England, Netherlands and Germany, but I do not know what

procedure is followed to order DNA tests in those countries. DR.

STIMSON - For international laboratories see http://www.eddnal.com or

http://www.genetests.org/ .

QUESTION -- Since I'm affected by CMT, are there any tests that can be

run on my daughter to see if she has the defective gene?

DR. GARCIA - We may need to know what type of CMT you have and what the

inherited pattern on you and your family is by doing a family pedigree.

The most precise way to know the exact type of CMT you have is by doing

a DNA test on you. If DNA has been done on you and it is positive, then

the same test is done on your daughter. If the test is negative and the

inheritance is autosomal dominant, then she can be assured that she will

not have the disease. If the test is positive, then she is going to

develop symptoms of the disease later on.

COMMENT -- I was adopted, it was hard to get answers.

DR. GARCIA -- If you are adopted, all you need is to get the DNA test.

QUESTION -- How long do you have to wait for the results of a DNA test?

DR. GARCIA -- DNA testing may take about four to six weeks depending on

the complexity of the tests. If you have CMT1A (PMP22 gene duplication),

the results will be obtained faster than if the lab has to do more tests

like sequencing for the entire gene or looking for other types of CMT.

Some labs recommend to order a panel but it is very expensive.

QUESTION -- What kind of test is needed to specify exactly the type of

my CMT?

DR. GARCIA -- DNA test obtained from a blood sample. There are two

commercial labs that perform the tests. Nerve conduction velocities only

differentiate between the type 1 and type 2.

QUESTION -- I have CMT. If I get married, will my CMT be inherited by my

children?

DR. GARCIA -- There are different types of inheritance in the Mendelian

transmission of diseases. Autosomal dominant (AD), autosomal recessive

(AR), and X-linked. The transmission pattern is different in each one.

If you have an AD form, each of your children have 50 percent chance of

been affected, in the AR form if you are a carrier your wife needs to be

a carrier of the disease as well and every child has a 25

percent chance of being affected; in the CMTX the disease is transmitted

from the mother's side of the family and the males are more affected

than the females. That is why the DNA test is so important. You also

need a family pedigree and a consultation with a genetic counselor.

QUESTION -- Are there any drugs or treatments that will slow the

development of contractures in my hands and feet?

DR. GARCIA -- Contractures are due to muscle weakness and lack of use.

Contractures are prevented by PT and stretching of the muscles.

Sometimes PT is not enough and patients may require surgical procedures

to release contracted tendons or to transplant strong muscles to weak

areas. You need to find a surgeon familiar with the

disease.

QUESTION -- I have a 6 1/2-year-old daughter with CMT type 1A and she

was diagnosed with high frequency hearing loss a year and a half ago.

Suddenly this month she complained of not being able to hear me, the TV

or anything very well. Her regular doctor found that the 4000 frequency

is now her best hearing instead of her worst. When you look at the

results chart, it had completely flipped upside down. We are in the

process of trying to find a cause and treatment, such as hearing aids.

How common is this in type 1A? And is it more common in children? Or the

even bigger question, is it unrelated to her CMT?

DR. GARCIA -- CMT1A is the most common form of CMT and is frequent in

children. Hearing problems are not frequent. However, Lupski,

M.D., Ph.D., Baylor College of Medicine, has found some mutation in some

families that are associated with deafness. Since she has CMT1A, I would

be careful and get an ENT specialist involved in the investigation of

her hearing loss.

QUESTION -- I am a 67 year-old male with a stent implant, using a

wheelchair for the past 17 years. I was taking Lipitor until I read an

article about it in Quest.I switched to Zetia but it's not as effective.

How bad is Lipitor?

COMMENT -- I recently took Lipitor and it caused my lower legs to cramp

significantly.

DR. GARCIA -- All statins (Lipitor is a statin) produce peripheral

neuropathies. If you already have a neuropathy, statins aggravate the

disease. It also depends on the dose used and the time you have been

using it. Some neuropathies resulting from the use of statins are

reversible, but some are not.

QUESTION -- Is creatine helpful for CMT?

DR. GARCIA -- Creatine is a muscle protein and helps to build up

muscles. I don't believe it helps CMT. CoQ10 may do a better job,

although there is no scientific evidence.

QUESTION -- Do you recommend any vitamins or supplements for CMT

patients?

DR. GARCIA -- I recommend using antioxidant vitamins such as Vitamins E

and C and CoQ10, but there is no scientific evidence they work. However,

they are safe to use.

QUESTION -- I have a male friend with CMT who has been taking yoga and

has begun to regain the feeling in his feet and hands. He says he sleeps

at night now, experiences much less pain and has a much greater range of

motion in his legs. He also has a more positive outlook on life in

general. Are you aware of any research or studies on the effects of yoga

on CMT patients?

DR. GARCIA -- Yoga may be helpful since you are stretching some muscles

and tendons. I do not know of any studies to confirm that. However, I

think it's a great idea for the muscle and the soul.

QUESTION -- I am a 62-year-old male who had a hip replacement five weeks

ago. Two weeks after surgery I had a sudden onset of weakness in my foot

on the operated side. I have high arches and hammer toes. A recent visit

to my neurologist with nerve and muscle conduction studies suggested the

possibility of CMT. There is no family history, and I have been active

for many years. Is the sudden onset of peroneal nerve

partial paralysis seen after hip replacement in a person with presumably

mild CMT?

DR. GARCIA -- During surgery there may be pressure in some areas of your

body. If you have HNPP (hereditary disorder to liability to pressure

palsies), you may be at high risk to developing focal paralysis like

yours. Most of these paralyses are acute and do not occur two weeks

later. The PMP22 duplication produces CMT1A. Deletion in the same area

produces the HNPP. You may need to be tested. There may be other reasons

for your postoperative neuropathies. Talk to your surgeon. NCV and

imaging studies can detect any focal abnormality on the nerve if there

is one.

QUESTION -- Is there any connection between CMT and migraine headaches?

DR. GARCIA -- There is no relationship between migraines and CMT that I

know of.

QUESTION -- There are many types of CMT identified by their different

genetic causes. What is the likelihood that when a treatment is

developed for one of the forms, it will have application to a number of

the types of CMT?

DR. GARCIA -- The treatments have to be individualized for each type.

Some are due to lack of proteins or to abnormal proteins; others are the

result of too much PMP22.

DR. STIMSON -- Treatments aimed at a specific gene defect causing CMT,

such as gene therapy, are likely to work for that specific form and not

others. It's hoped that other treatments under investigation, such as

giving nerve growth factors to regenerate damaged nerves, would work for

all forms of CMT.

QUESTION -- I see the signs of CMT in my sister's two children. I keep

telling her to get them tested, but she seems to be in denial. Is there

an advantage in knowing early?

DR. GARCIA -- It is very important to know what type you have because

when some treatment is developed you will know if it is applicable to

your particular type. There is no rush to do it now.

QUESTION -- Do you anticipate that an effective treatment would have to

be in the form of gene therapy or would there be other types of

therapies \that might be of potential benefit?

DR. GARCIA -- Gene therapy may be good for some types, but for the most

frequent type, CMT1A, because a genetic duplication causes it - too much

of a protein - not a deficient or replacement situation, medical

treatment in the form of drug may be a better approach.

DR. STIMSON -- Thanks, Dr. , for sharing your wisdom with us. And

thanks to everyone else for the great questions.

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