Few Multiple Sclerosis questions and their answers

Nitin K Sethi, MD

Assistant Professor of Neurology

NYP-Weill Cornell Medical Center

New York, NY 10065

One of my readers Lisa asked me some very specific MS questions. Since I feel these questions shall be on many MS patients minds I am reproducing them here. Here are the questions followed by my answers. Thank you Lisa!!!

  1. Lisa on September 17, 2008 said:

Hi, I have enjoyed reading the information you posted. I have a few questions of my own:

At this point, I have an MRI with 8 lesions, one possibly of which is tumefactive MS, a postive LP for oligoclonal bands, and my neurologist has diagnosed me with “clinically isolated syndrome”…not full blown MS at this point, but still wants to begin treatment.

1. Is tumefactive MS considered more fatal or harder to treat than “regular” MS?

2. How many oligoclonal bands are needed for a low amount? High amount? My report states greater than 3 bands. Why is there not a specific number given?

3. I have been given the choice between Rebif and Copaxone. Which is the better treatment?

  1. 7 braindiseases on September 18, 2008 said:

Dear Lisa,
thank you for writing in. You ask some very specific questions and that is what I shall attempt to answer. I am not sure why your doctor has stil labelled you as a clinically isolated syndrome (likely it is because you have had only one clinical attack suggestive of MS). Your MRI though does show dissemination of the disease in space (you can read more about the clinical diagnosis of MS on my website
http://braindiseases.info) and you have more than 3 oligoclonal bands in your CSF. Now to answer your first question. Some patients have large sized demyelinating plaques (lesions) on their MRI. This is commonly referred to as tumefactive MS (because on the MRI, the lesion is large and resembles a tumor more which it has to be differentiated). There is some data to suggest that MS patients with tumefactive disease have a more aggressive disease course. Though I have to add that this data is not robust.
Oligoclonal bands are frequently present in the CSF of MS patients. Here I have to add that oligoclonal bands can be seen in many other conditions other than MS hence one has to make sure that they are present only in the CSF and not in the blood (In MS these bands are produced intrathecally meaning present only in CSF but not in blood). One study suggested that low or absent number of oligoclonal bands in the cerebrospinal fluid at the time of diagnosis predicts a better prognosis. However quantification of oligoclonal bands in the CSF remains an insensitive prognostic indicator and hence should not be used to influence decisions regarding treatment.
Now to your third question. There is some evidence to suggest that higher dose interferon (Betaseron/ Rebif) are more effective as compared to lower dose interferon. The interferons as well as Copaxone are recommened for initial treatment of relapsing remitting MS. Most of the times it is the patient’s lifestyle, easy of administration and side-effect profile which determines the choice between them.
I hope that helps you out and feel free to write again. I wish you the best.

Personal Regards,
Nitin Sethi, MD

MS treatment related issues

Let us continue to talk about some issues which arise during the treatment of multiple sclerosis.


1) How does the disease pan out: Let me try to give you a broad overview of what to expect if you have been diagnosed with multiple sclerosis. I want to stress that this by no way applies to every patient, because each patient’s disease behaves in its own unique way. Initially as I stated earlier, multiple sclerosis has a remitting and relapsing course. You have an attack, it causes some deficits (weakness, numbess, vision loss or gait and balance problems) and then the attack remits and patient may come back to his or her baseline functioning (meaning there are no residual deficits left behind). When multiple sclerosis behaves in this manner it is said to have a relapsing and remitting course (RELAPSING AND REMITTING MULTIPLE SCLEROSIS OR RRMS).

As the disease progresses though and the patient continues to have more attacks, it is seen that the patient does not remit or revert back to the baseline (meaning that some deficits are left behind like some residual weakness or numbness, some problems with balance, tremors etc). When this occurs the patient starts to incur some disability and the disease is said to enter a progressive course (SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS OR SPMS).

As I stated earlier patients in SPMS stage start to get disabled whether it is due to excessive weakness, fatigue or problems with balance or a disabling tremor. As doctors we try to grade their progression in this stage and there are various scales we use. One of the most commonly used scale is the Expanded Disablility Status Score or EDSS. This is a 10 point scale and when a patient reaches midway like around 5 to 6, he or she starts to need assistance with walking and further on may need a wheelchair for ambulation.

The intention behind using the interferons and other immunomodulatory drugs like copolymer (Copaxone) is to prevent or rather delay the progression from a RRMS to a SPMS.

Hence the rationale behind treating all patients aggressively from the onset. Once the patient is in a SPMS state, the medications are continued and different medications might be added to try to halt and delay the disease progression.


Till now we do not have any drugs which change the natural history of the disease (meaning cure it!!), all we have are medications which may delay the progression.


 There are a certain subgroup of MS patients who have a progressive downhill course right from the onset of the disease (meaning in them the disease does not follow a relapsing and remitting pattern rather they continue to incur more and more neurological deficits). These patients as you can imagine have a poorer outcome and this pattern of disease progression has been referred to PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS OR PPMS


Healthy brain and a healthy mind

Issues that come up during MS treatment

Let us now talk about some issues which come up when you are diagnosed with MS.

1) What happens next?

so you are diagnosed with multiple sclerosis what now? Do you need to start  some multiple sclerosis drug immediately? This is a tough question and something which only your doctor can best decide after reviewing all investigations and MRI brain scans. Multiple sclerosis is in its typical form has a relapsing and remitting course. By that I mean, a patient may present with an acute attack of MS like weakness or unsteadiness or loss of vision in an eye (optic neuritis) but then the attack remits and the patient may come back to his or her baseline with at times no residual signs and symptoms. Then there may be a length of time when the patient experiences no fresh attacks. So the question is when do we start treating the disease. Research has shown that even though the patient may have no clinical attack (no overt manifestations of MS), the disease is still relentless and proceeding in the brain. How do we know this? Simple if you repeat the MRI in even an asymptomatic patient, the MRI shall show new lesions (meaning new plaques are seen in the brain MRI suggesting radiological progression of the disease).

Further research has also shown that these lesions (plaques) in the brain add up and contribute to the final disability. The more the number of plaques in the brain (we refer to this as the plaque burden), the more is the final disability and the cognitive difficulties experienced by the patient.

So now the thinking among MS specialists is to treat early and to treat aggressively. The longer you wait, the more is the damage to the myelin and axons (nerve bundles) in the brain. That said and done each patient’s disease behaves in a unique way. There are a small group of patients who have what is called as benign MS. These patients show little or no disease progression over years both clinically and radiologically. Why some patients have this benign form of the disease no one knows but remember it is very difficult if not impossible to know at the onset if a patient is going to have a benign form of MS or not. Hence usually MS specialists would recommend treating right from the onset.

2) Which interferon to use and which is better?

This is another issue which comes up during MS treatment. There are 3 different kinds of interferon available on the market: interferon beta 1b (marketed as Betaseron) and interferon beta 1a (marketed as Avonex and Rebiff).  Without going too much into detail, there is some evidence to suggest that interferon beta 1 b (Betaseron) may be more effective than interferon beta 1a (Avonex).

Betaseron has to be given three times a week (every alternate day) and it has to be injected subcutaneously (under the skin). Avonex on the other hand needs to be given just once a week and it is given intramuscular (inside the muscle and thus more painful shot than a subcutaneous shot). That said and done since Avonex is given once a week it is far more convenient and does not interfere with a patient’s lifestyle as compared to something which needs to be given three times a week.

There is also the issue of neutralizing antibody formation. Simply put it has been seen that if someone takes interferon for a long time, the body starts to form antibodies against it. These antibodies have been referred to as neutralizing antibodies and if a patient has a high titre of these antibodies, it may neutralize the effect of the interferon (meaning make the interferon less effective). Some research has shown the patient’s who take Betaseron develop neutralizing antibodies at a higher rate as compared to those on Avonex or Rebiff. Again your doctor shall guide you through this decision making process.


Need more information: email me at neurologistnyc@yahoo.com

 Visit my website: http://braindiseases.info  if you seek further information on some common neurological conditions.