MSAA: Publications - The Motivator: Winter/Spring 2007 - Ask the Doctor
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Home > MSAA Publications > The Motivator > The Motivator: Winter/Spring 2007 > Ask the Doctor
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Ask the Doctor

By Dr. Jack Burks
Chief Medical Officer for MSAA

Dr. Jack Burks Photo
Dr. Jack Burks

Q: What is your opinion, in regards to taking a test for antibodies, to see if one's medication is still working? My doctor feels this test doesn't mean anything.

A: This is a very controversial area. The American Academy of Neurology (AAN) reviewed this subject scientifically a few years ago. This panel of experts concluded that the utility of even measuring antibodies with interferons was uncertain, due to the fact that study results have been conflicting and confusing. Some studies show an association between the presence of antibodies in patients who are not responding fully to a treatment. Other studies indicate the opposite trend, i.e., antibodies, especially early in the treatment, are associated with a better response to therapy. The most recent study indicates that patients who are not responding well to an interferon, may be less likely to have high levels of antibodies compared to an overall population of treated patients. You can see why I am not yet certain as to the role of antibodies, if any, in interferon treatment. Except for one study, antibodies to Copaxone® (glatiramer acetate) have not been linked to suboptimal treatment response.

Therefore, I do not order antibody tests to determine the effectiveness of a patient's medication. In my opinion, if a patient is doing well on his or her medication, I would not switch therapies, even if antibodies were present. On the other hand, if a patient is not doing well on a therapy, I change treatments even if antibody tests were negative. Other experts order antibody tests routinely. The controversy will continue until the scientific data are more complete.

In summary, I make clinical decisions based on a patient's response to a drug, and not on any one test. The AAN is presently reviewing the subject for a second time and I await their additional recommendations, if any.

Q: I am a 59-year-old man with primary-progressive MS (PPMS). I have had MS for more than 30 years, I am not on any MS drugs (just those for symptom management), and I am no longer ambulatory. Unlike most people with MS, I am cold most of the time and wear sweat suits throughout the year. I haven't had an MRI of the brain since 1990. Do you have any suggestions as to what I should do next?

A: Unfortunately, there is no proven treatment for PPMS, which is diagnosed in 10 percent of the MS population. Future treatments may be helpful, but at this time we need a better understanding of the underlying cause of this form of MS. In a recent clinical trial, Copaxone was studied in PPMS but the trial was stopped early due to lack of benefit. The potentially good news is that a clinical trial of Rituxan® (rituximab), by Genentech and Biogen Idec, is underway for people with PPMS. This drug is aimed at "B" lymphocytes (makers of antibodies), which are different from "T" lymphocytes (involved with inflammation), which are the targets in many relapsing-remitting MS (RRMS) trials.

There is reason for hope. We know that PPMS is more of a degenerative disease, while the more common relapsing-remitting (RR) type of MS is primarily an inflammatory disease. While current MS treatments focus on inflammation, future treatments will also be aimed at reversing the damage to the myelin (protective covering of the nerve) and the nerve fibers. These types of repair are referred to as remyelination and regeneration. Developing such treatments is an urgent goal in MS research, but we are not there yet. Stem cells may also prove to be of benefit in these areas of remyelination and regeneration of nerve fibers.

Your symptom of feeling cold is not that uncommon in MS. Some people actually feel they function better when they feel cooler than warmer. Some use cooling devices to feel better. However, I would look for other causes of feeling cold, such as low thyroid. If wearing a sweat suit relieves the cold sensation, I would not pursue other treatments.

As for an MRI, ask your neurologist if he or she thinks that an MRI of the brain and possibly the spinal cord could be helpful. I might consider another MRI after 17 years on the unlikely chance that I might find something additional that may be adding to your disability (such as spinal-canal narrowing or a disc problem).

Q: I am having a favorable experience on Novantrone. I have not had any cardiac-related issues, and I attribute this to receiving Zinecard (intravenously) prior to the Novantrone infusion. I understand that Zinecard is a cardiac protector. Can you tell me any more about this drug, and are others using this in conjunction with Novantrone?

A: Novantrone® (mitoxantrone) is an anti-cancer drug that has been used successfully to help many MS patients with worsening MS who have not responded adequately to treatment with the other current immunomodulating therapies (Avonex® [interferon beta-1a], Betaseron® [interferon beta-1b], Rebif® [interferon beta-1a], or Copaxone). The decision to use Novantrone therapy is highly individualized and certain patients seem to respond better than others.

Since Novantrone is an anti-cancer drug, concerns of side effects weigh in the decision-making process. The major side effects are potential loss of menstrual periods (amenorrhea), heart toxicity (which may be irreversible), and the rare chance of getting leukemia. The risk of heart toxicity may possibly be lessened by Zinecard® (dexrazoxane), which has been used to protect cancer patients from heart toxicity from drugs similar to Novantrone.

In 2006, a study at the University of Michigan using Zinecard plus Novantrone in MS patients was published. After one year of therapy, in which Novantrone (with or without Zinecard) was given on a quarterly basis, patients also receiving Zinecard with Novantrone had a less severe decline in their heart function, although both groups had some minimal decline in heart function. None of the patients in either group had symptoms of heart disease in this study. The average heart-function reduction in both groups was less than 10 percent. None of the 28 patients treated with Zinecard had a heart-function decrease greater than 10 percent, whereas seven of 19 patients who did not get Zinecard with their Novantrone had a heart-function decrease greater than 10 percent.

Therefore, in this series, patients demonstrated some heart protective effect of Zinecard in conjunction with Novantrone. Nonetheless, Zinecard is not yet used routinely with Novantrone by many neurologists, since it is not FDA approved for this purpose. In addition, Zinecard has its own independent immunosuppressive effect, which must be evaluated with the immunosuppressive effects of Novantrone. Patients with concomitant kidney disease must be especially careful when using Zinecard. Its safety and effectiveness has not been established in pediatric or geriatric patients.

In summary, Zinecard may be helpful in reducing heart toxicity of Novantrone. The additional immunosuppressive effect of Zinecard could potentially add to the effectiveness of Novantrone or it may cause unwanted additional immunosuppression. I will quote the last sentence of the 2006 paper, "A larger randomized, prospective clinical trial of Novantrone with and without Zinecard seems warranted before considering Zinecard for general use." 1

As a reminder, the updated FDA recommendation is that heart testing should be done in all patients treated with Novantrone prior to taking each dose irrespective of whether the patient has signs of heart failure.

1 Bernitsas E, Wei W, Mikol D, "Suppression of Mitoxantrone Cardio-toxicity in Multiple Sclerosis Patients by Dexrazoxane," Ann Neurol. 2006;59:206-209.

Q: After more than 10 years of vague symptoms, I had a severe attack and was diagnosed with MS. That severe attack left me with permanent disability. I began Copaxone, had one exacerbation about a year later, and since then just some very slight flare-ups, which over time have led to some additional disability. My MRIs have been pretty stable.

When I inquired about Tysabri, my present neurologist said that she did not think it was appropriate as I have the secondary-progressive type of MS. I have already scheduled an appointment for a second opinion with a TOUCH neurologist, but I'd like an objective opinion. First, what is an honest assessment of where I am; and second, is Tysabri appropriate for someone in this stage?

A: Tysabri® (natalizumab) has not been tested in secondary-progressive MS (SPMS). This form of MS is primarily a disease of degeneration and not inflammation (as seen in relapsing-remitting MS, or RRMS). Theoretically, Tysabri may not be helpful in SPMS since it is designed to treat inflammation specifically. However, if you are still having considerable inflammation in the brain (as seen on an MRI) or still having relapses (which indicate inflammation), Tysabri may be helpful, although it has not yet been proven effective in progressive disease. This concern likely explains your neurologist's reluctance to recommend Tysabri, in addition to its rare but potential fatal toxicity. If your doctor feels you are not responding well to Copaxone, interferon therapy or Novantrone are other options.

In summary, Tysabri is designed to treat inflammation while SPMS tends to be more a degenerative than an inflammatory disease. We do not know yet if Tysabri will benefit patients with secondary-progressive disease. Interferons and Novantrone have both been tested; some studies have shown a beneficial effect, especially in early secondary-progressive disease. A comparison of the risks as well as potential benefits of these three potential therapies (Tysabri, interferons, and Novantrone) should also be part of the discussion with your neurologist.

Q: I have had MS for 30 years and was told that it is now (and has been for 20 years) the secondary-progressive type of MS. I am in a wheelchair and had to retire two years ago. I was taking interferons 12 years ago. The neurologist that I see now wants to put me back on an interferon. What are your thoughts on this?

A: I would refer you to the previous question that involves a patient with secondary-progressive MS (SPMS). If your neurologist wants to put you back on an interferon, I assume that he or she has reason to believe you have a chance to respond to this therapy again. Interferons are a reasonable option, if you are having evidence of inflammation in addition to the degeneration. Evidence of inflammation may be apparent on the MRI or if you are still having relapses. Other treatment options include Novantrone and Copaxone, since they are different classes of therapy than the interferons. However, like Tysabri, no clinical trial evidence is available on the effectiveness of Copaxone in SPMS. Again, weigh the risks versus the benefits of all potential medications.

Q: I have had MS for five years and I take an interferon. I have tried many pain, anti-depressant, and sleep medications, but I am still experiencing a lot of pain throughout my body as well as my worst symptom, which is extreme nervousness. So far, no medication has helped. I feel like something is racing through my body and I can't stop it. Is there any way you can advise me? I seriously need your help.

A: Pain throughout the body, extreme nervousness, and a racing sensation through the body are very disconcerting and drastically affect the quality of life for anyone, including someone with MS. I do not know if you have tried all types of pain and "nervousness" medications yet. If "stuck," your doctor may refer you to an expert in these fields. Did you have any of these symptoms before your MS began or before starting interferon treatment? Has your doctor considered having you take a "drug holiday" from the interferon, to see if these symptoms improve? Have you tried alternative treatments such as biofeedback, self-hypnosis, visual imagery, yoga, massage, meditation, and other non-traditional therapies? If your symptoms are related to your interferon therapy, Copaxone® is another option.

Some comprehensive MS centers have multidisciplinary expertise in these areas. You may find a listing of centers belonging to the Consortium of MS Centers (CMSC) by visiting their website at and selecting the "MS Centers Directory" listed on the left side of the screen. If you do not have access to the internet, please contact MSAA's Helpline at (800) 532-7667 to speak with a Helpline consultant, who would be happy to assist you in locating an MS center in your area.

Q: I was diagnosed with MS in 1993. Recently I had a bone-density test done and my doctor has recommended I increase my consumption of milk and other dairy products. I am also taking Didrocal® [a medication used to treat osteoporosis]. Since I have increased my consumption of dairy products, my MS symptoms have worsened. Could this worsening of my symptoms be related to the dairy products, and are there other means to increase my calcium intake that would be as beneficial as eating dairy products?

A: I cannot determine if your consumption of dairy products has caused a worsening of your MS symptoms. Some independent researchers have looked into a possible connection between dairy products and MS, (see the Fall 2004 issue of The Motivator), but dairy-product consumption has not been linked to worsening MS in any double-blinded, placebo-controlled clinical trials with MS patients.

Nonetheless, I would ask your doctor about other means of increasing your calcium intake. He or she may refer you to a specialist in this area for a more definitive opinion. As you know, calcium supplements are available in all supermarkets and health-food stores. However, your situation may call for advice that is more specific. Unfortunately, your worsening may be due to the natural course of your MS. Therefore, I would ask your neurologist to evaluate your current MS treatment. It might be time to consider changing your therapy or at least getting another MRI to document the degree of worsening of your MS.

Jack Burks, MD, is a neurologist who specializes in MS. He is chief medical officer for MSAA, as well as president of the Multiple Sclerosis Alliance. Additionally, Dr. Burks is a clinical professor of medicine in neurology at the University of Nevada School of Medicine in Reno, Nevada, and a member of the Medical Advisory Board of the National MS Society. He has edited two textbooks on MS, and in the 1970s, Dr. Burks established the Rocky Mountain MS Center.

To Submit Questions to Ask the Doctor...

If you have a question that you would like to ask, please submit your question to:

Questions for Ask the Doctor
Attn: Andrea Borkowski
c/o Dr. Jack Burks
375 Kings Highway North
Cherry Hill, NJ 08034

Readers may also send in questions via email to Please be sure to write "Ask the Doctor" in the subject line.


Last Updated on Monday, 22 June 2015 10:34