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Do You Need to Exercise if you have Multiple Sclerosis?

12/31/2013

 
Q.  Is exercise really that important for MS, and why? I hate exercising, and when I feel tired and crampy I feel more like resting than torturing my body even more.

A.  First, let me provide you with the reasons that exercise is important for people with MS and then let me address your specific concerns. The overall answer is that exercise is probably the most important therapy for MS and serves as the platform for all other treatment modalities.


  1. Exercise is the only treatment known to improve function in MS patients
  2. Exercise preserves neuronal reserve and provides a buffer against disease progression
  3. Exercise improves well being and mood
  4. Exercise improves overall health and protects you from other conditions (e.g. cardiovascular disease , diabetes etc) that will worsen your MS and your quality of life. 
  5. Exercise serves as a deterrent to other bad health behaviors; you don't see a lot of smokers who regularly exercise
  6. Exercise will help prevent other MS related complications even in the absence of other medical problems. For instance, exercise will help preserve bone density in more disabled patients and limit the development of chronic pain syndromes

This being said, some people have difficulty initiating and continuing exercise programs for reasons both related and unrelated to their MS. Since the perceived barriers to exercise are almost too numerous to list, I find it far easier to list some core principles to follow:

  1. Just do it  is the maxim you must always follow; Try to exercise 5 days a week and never let yourself fall below 3 days a week unless you are significantly ill or injured. Even an MS relapse should not take you away from exercise for long. You must find the time to fit this into your life and make sure those around you understand exercise is as important as anything else you need to do. This will require you to make some life choices and possibly some sacrifices at the beginning. I guarentee you will not consider exercising a sacrifice after the first 6 months, if not sooner.
  2. Start low and go slow. Some individuals are unable to perform aerobic exercise programs or even progressive resistance training for more than 5 minutes at the beginning. This could be due to other health conditions or just MS related fatigue. If this is the case, begin at 5 or 10 minutes and gradually increase on a weekly basis even if only by 1 minute at week. Eventually you will reach at least 30 minutes of exercise.  You should feel moderately but no severely tired after completing and exercise routine. As the Buddhist proverbs states, " A journey of a thousand miles begins with a single step."
  3. Do exercise that you enjoy or find a way to enjoy it.   The types of exercise programs are almost too numerous to mention; some are individual and some involve groups; some can be done without leaving your home. Many incorporate games or other social activities. Be creative. Despite the many options some people tell me they hate all exercise and would prefer to just watch TV. I say fine, watch TV while walking on a treadmill or using an exercise bike. If you exercise every time you watched TV, you would probably exercise 4 hours a day !
  4. If heat intolerant use methods to keep your body temperature down : This is particularly true of MS patients and the main reason that many patients prefer swimming or pool walking for exercise. Immersion in the water during and after exercise,  moderates any increase in core body temperature. Other methods of cooling include air-conditioning, fans and cooling collars or hats.
  5. Always include a combination of stretching, aerobics and progressive resistance (weight training)
  6. Get help if you need it from a physical therapist or a trainer
  7. If you fall off the wagon or have a setback, just start over again
  8. Make sure everyone in your family or close to you understands the importance of exercise and participates. If you haven't noticed already socialized behavior is reinforcing. Those who continue to smoke tend to hang out with smokers and those who regularly exercise tend to hand out with those who exercise. In each case the social interaction is supportive and reinforces the behavior. Recent evidence suggests that even overweight people tend to hang out with other overweight individuals.  To effect change in yourself often requires a change in those around you.

Revere (Rip) Kinkel MD
Director of the Multiple Sclerosis Program
Professor of Clinical Neurosciences
University of California San Diego

Leukapheresis and Multiple Sclerosis?

12/23/2013

 
Q:  Here's a question for Dr. Kinkel. Do you think that leukapheresis could be helpful to remove the T-cells accumulated in blood during Tysabri treatment, and perhaps prevent rebound relapses? I have just seen some reports of its use in Crohn's, and I thought about similarities between the two diseases. Thanks!!! Ana

A:  Now that is one great idea that I never considered. For those of you who do not know, leukocytapheresis is a technique used to selectively remove white blood cells from the circulation and return the rest of your blood cell types and plasma back to the patient. Blood is removed in the usual manner and filtered to selectively remove either all the white blood cells or a subset of white blood cells by selective absorbance. Leukocytapheresis has been used to treat inflammatory bowel disease for more than a decade but has not been applied to MS treatment. The person must undergo treatment once a week for up to several months with each treatment requiring up to 3 hours. The real question in my mind is whether this would be an acceptable approach to prevent Tysabri withdrawal relapses. Definitely something to look into. Thanks again for the idea. 

- Dr. Kinkel

Pregnancy, MS and IV Ig

12/21/2013

 
Q.  I just read about some neurologists having their pregnant patients, that just discontinued Tysabri, on IV Ig throughout pregnancy to avoid rebound relapses. What's your opinion on this? Thank you!

A.  For pregnancy, neurologists take many approaches to prevent Tysabri withdrawal relapses. I previously discussed in another blog tapering off Tysabri and monitoring for the return of disease activity before getting pregnant. I cannot argue with the use of IV Ig in this situation as well but recall that IV Ig treatment itself is controversial in MS patients. The majority of studies suggest minimal benefit from this treatment, so I would not expect it to have much of a benefit in this situation. However, it is relatively safe in this situation and I think it is the safety of IV Ig that is dictating its use in this setting, not its effectiveness.

--Dr. Kinkel

PLEASE NOTE:  The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.  Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition.

Tysabri and Relapses

12/20/2013

 
Question:  Is there a way you would be able to tell if certain patients would be more susceptible to having relapses? For example, if a patient had certain symptoms before starting Tysabri?

Answer:  Susceptibility to relapses after stopping Tysabri is somewhat unpredictable. In general, people with active disease in the year prior to starting Tysabri are much more prone to these Tysabri withdrawal relapses. Active disease would include:

1. At least 1 enhancing or new T2 lesion on more than 1 MRI scan in the prior year  or more than 1 enhancing or new T2 lesion on an MRI prior to starting tysabri while still receiving another therapy
or
2. One moderate to severe  relapse or more than one mild relapse in the year prior to starting tysabri

Unfortunately this criteria does not predict even the majority of people with relapses after stopping Tysabri


PLEASE NOTE:  The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.  Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition.

Stem Cell Treatment and Multiple Sclerosis

12/19/2013

 
This question just came in from an MS patient:  "What can you tell me about stem cells? I know they are still under research but is it being researched for stopping progression of primary MS? Someone is on my back to do this and I am not too keen on it."

There are many different types of stem cells that are being studied in MS patients. Most are intended to reset the immune response against the nervous system in MS while others, in earlier stages of development, are intended to repair damage in the nervous system. None have been proven more effective than current treatments at halting disease progression, the main goal of treatment. These treatments should only be considered experimental in MS patients at this time.

 

Does Tysabri Cross the Placental Barrier?

12/18/2013

 
Tysabri (natalizumab) is a humanized IgG class monoclonal antibody that will cross the placenta just like most other antibodies. Doses much higher than those used to treat MS may cause  adverse effects on an unborn animal but these problems are not readily apparent when lower doses are given to lab animals. The situation in humans is totally unknown except for small case series reporting accidental pregnancy outcomes in woman taking tysabri for their MS. No obvious fetal abnormalities or poor pregnancy outcomes have yet been linked to tysabri in these small case series but it is too early to be sure. This is why Tysabri remains pregnancy category C.

Immune System and Tysabri -- Multiple Sclerosis

12/17/2013

 
Q.  Is Tysabri modifying the general immune system, or only the part concerning brain, spinal cord and gut (like in Crohn's)? If not, then we should not be more susceptible to "usual" infections like colds, is that correct?

A.  Tysabri primarily binds to an adhesion molecule on lymphocytes that is required for normal trafficking of these lymphocytes across endothelial barriers and into tissue, particularly the gut and brain. It may impact on normal lymphocyte trafficking into other tissue compartments as well and may affect normal immune regulation. Despite these effects Tysabri causes only a slight  increase in the risk of common infections like colds and shingles.

--Dr Kinkel


PLEASE NOTE:  The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.  Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition.

Should I get a Shingles vaccine if I have Multiple Sclerosis?

12/13/2013

 
Question from and MS patient:  "I am in my early 60s.  Should I get a Shingles vaccine?  I have PPMS and am worried because it is a live virus."

Answer:  The Shingles vaccine is a live attenuated vaccine with a theoretical potential for causing a modified case of chicken pox if given to immunosuppressed individuals. Remember MS patients are not immunosuppressed unless they are given a treatment that suppresses their immune system.

The shingles vaccine has been shown to reduce the risk of shingles by over 60% in patients between 60 and 69 years of age and decrease the severity of shingles in those who do experience shingles despite being vaccinated. This means it is a good idea for most people over the age of 60 to get this vaccine.  The National MS Society and other groups recommend this vaccine in MS patients over the age of 60, but caution against giving this vaccine to patients on therapies that suppress the immune system.

However, a very large study reported in 2012 reported that the shingles vaccine was highly effective and without risk in patients with autoimmune conditions (rheumatoid arthritis, psoriasis and others) on immunosuppressive treatments. Because of this study I tend to recommend the shingles vaccine in almost all MS patients over the age of 60. It is certainly safest and most effective to give the shingles vaccine before beginning an immunosuppressive or immunomodulatory therapy that can increase the risk of shingles, but this is sometimes not possible.


--Dr. Kinkel


PLEASE NOTE:  The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.  Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition.

Changing Outcome Measures for Multiple Sclerosis

12/12/2013

 
So I am heading off to Las Vegas for an MS conference this weekend to discuss the development of newer and more meaningful outcome measures in MS. For the past 20 years we have used relapse rates (the number of relapses during the trial divided by the duration of the trial)  as the main outcome measure in our clinical trials. For those of you who have read my blogs you already know this is not the best way to determine the effectiveness of a therapy; first, relapse rates are weakly linked to future disability, the main thing we are trying to prevent with our treatments; second, relapse rates naturally decrease over time making it difficult to determine if a person is staying relapse free because they are getting older or because they are taking a useful therapy. This also creates a problem determining the effectiveness of a drug in patients who rarely experience valid relapses (think progressive MS).  Most trials attempt to solve the latter problem by attempting to measure the degree of disability over time, but the main disability outcome measure in use (called the EDSS) is insensitive to change over the short duration (2 years) of a clinical trial. In all fairness to the pharmaceutical companies they are well aware of the problems with these outcome measures, but the FDA still requires them to use them in phase III clinical trials. This means that following the completion of a successful phase III trial and approval of a drug by the FDA, we still do not know enough about the long term effectiveness of the drug compared to a placebo and virtually nothing about the comparative effectiveness of different therapies. It has become commonplace for most therapies to report 40-50% reductions in relapse rates, 20-30 % reductions in disability progressive and 70-80% reduction in new MRI lesions. Very few therapies report group benefits in excess of these numbers. We also know very little about the probable effectiveness of a drug in any individual patient. Our goal in the future is to take the guesswork out of these treatment decisions but to do so will require new and innovative outcome measures and trial designs. More later. -- Dr. Kinkel

How Do you Decide on a Disease Modifying Therapy for Multiple Sclerosis?

12/11/2013

 
Written by Revere (Rip) Kinkel MD
Director of the Multiple Sclerosis Program
Professor of Clinical Neurosciences
University of California San Diego


I am afraid this blog has the potential to be overly controversial, so I will tread softly with my comments. Here we go:

Patients often exclaim (more often it’s a complaint) during our initial encounter that their prior physician sent them home with 3 or 4 drug company pamphlets to read with instructions to call the office back and let them know which treatment they prefer.  Other patients tell me that their prior physician gave them no choice and recommended a specific treatment.

These approaches represent two ends of a spectrum that I find lacking.  Rarely, do I hear of patients being informed of the pros and cons of available therapies, and even more rarely do I hear of any prior discussion of the short and long term goals of therapy.  While it is true that we have very little useful comparative effectiveness data to help patients and physicians choose a therapy, there is data available to guide us in these decisions.

So without comparing drugs let’s consider some of the factors that should go into the decision making process.  All of these factors should be considered in your selection of treatment

  1. Where are you in the course of the illness? Are you a patient newly diagnosed with no evident impairment, mild disease activity, and no prior treatments, or are you a patient many years into the disease with obvious disability and often with many prior treatment trials?  The former patient is a good candidate for a platform therapy (interferon or copaxone) whereas this may not be true for the latter patient.
  2. Do you have a variant of MS that may not respond to certain therapies or at a minimum may require additional monitoring? For instance, some patients with Neuromyelitis optica receive an inaccurate diagnose of MS;  these patients will not respond well to standard injectable therapies. Similarly, there is some evidence that African Americans with MS may not respond well to interferons. Although this evidence is not strong, it should at least be considered in therapeutic decisions.
  3. Do you have any comorbid conditions or risk factors that may impact treatment? For instance, a patient with Type II diabetes is at much higher risk for complications from both MS and from treatments like corticosteroids.  I tend to treat these patients earlier with highly active MS therapies (Tysabri) to reduce the combined risk of complications from both conditions. More obvious examples include the patient with cardiovascular risk factors not being a good candidate for fingolimod (Gilenya) or the patient with chronic irritable bowel syndrome or significant gastritis not being the best candidate for dimethylfumarate (Tecfidera). Patients with frequent migraine or headache disorders can find interferon treatment challenging.
  4. Are you on other medications that may interact with one of the MS treatments? While this problem is less common with currently available treatments there are some examples: for instance, fingolimod (Gilenya) should not be used in patients on certain anti-arrhythmic therapy.
  5. Do you have any plans for pregnancy in the near future, usually the next 2-3 years? If so, your MS specialist will need to create an appropriate treatment plan to take this into account. For instance, treatment with teriflunomide (Aubagio) would not be the best choice in this circumstance.
  6. Do you have injection phobia?
  7. Are there any unique lifestyle issues such as the need to travel frequently? Daily or every other day injections can be a challenge in this circumstance.
  8. In the near future we will be using more biomarkers to help with treatment decisions. For now, the most common biomarkers for both therapy selection and monitoring include anti-interferon neutralizing antibodies in interferon treated patients, anti JCV antibodies in patients considering Tysabri and anti-Tysabri antibodies in Tysabri treatment patients.
  9. Lastly, we cannot underestimate the role of insurance companies in treatment decisions for right or wrong reasons. Many plans now require a step approach to therapy insisting that a patient fail one or more injectable therapies before an oral therapy or highly active therapy can be considered. You must develop a plan with your MS specialist to deal with these restrictions in a way that does not interfere with your ability to get the best treatment for your situation.

Next, you must consider the goals of therapy and have these clearly in mind before you begin treatment. Otherwise you will never know when to consider altering your therapy in the future. Goals will also depend on where you are in the course of the disease and your prior response to therapy. With some therapies there is good evidence to support switching treatment if there is continued MRI activity 6 to 12 months after starting treatment.  This is particularly well documented for interferon therapy. Of course this is only useful in monitoring patients early in the course of the disease. Later in the disease course, it is less common to see new MRI lesions or relapses even with ineffective treatment. For these patients, an appropriate goal may include maintaining the ability to walk a certain way for a certain interval of time or preventing the spread of the disease from the legs to the hands. These types of goals will also help you seek out the most appropriate rehabilitative therapies to complement pharmacological management.


I hope these thoughts help you in the process of considering different treatment choices. The issues are far more numerous and nuanced than I can detail in this blog, but this framework will allow you to carry out a more thoughtful decision making process with your family and physician.



Revere (Rip) Kinkel MD
Director of the Multiple Sclerosis Program
Professor of Clinical Neurosciences
University of California San Diego

PLEASE NOTE:  The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.  Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition.

To Treat (an MS relapse) or Not to Treat with Steroids

12/2/2013

2 Comments

 
To treat [a relapse] or not to treat [a relapse]...that is the question.

This is a question that has vexed neurologists and patients for decades. Although there is still no consensus based on evidence, there is a pattern of advice provided by most MS specialists that is generally consistent.

First, some definitions and information regarding relapses and new lesions on MRI: a relapse is the development of new or worsening neurological symptoms in an MS patient, usually with confirmatory findings on examination, that lasts for more than 48 hours and is NOT caused by a fever, medication or another medical problem. Relapses can last for less than 48 hours but do not require any intervention. A relapse typically continues to worsen over several days if not weeks before stabilizing and improving. In fact the initial stage of MS is called relapsing remitting because following a relapse a patient normally recovers without treatment, although the extent of recovery varies from patient to patient and relapse to relapse. The rule of thumb regarding relapse recovery is that it takes longer to recover from relapses that develop over a longer period of time. Patients who awaken with the sudden onset of symptoms at their worst point, such as being blind in one eye, often recover faster and more completely than a person who develops lesser symptoms over an interval of weeks.

Relapses DO NOT require the presence of Gadolinium-enhancing lesions on MRI. In fact some of the worst relapses I have observed occurred in patients with large new areas of involvement on MRI that did not enhance following the administration of contrast. Similarly, the presence of gadolinium enhancing lesions (contrast enhancement) on MRI does not mean you are having a relapse. In short, relapses are only defined by symptoms and findings determined by an expert evaluator (often this is the patient after years of experience) to be caused by new or worsening areas of inflammatory demyelination in the CNS.

The mainstay of treatment for relapses continues to be corticosteroids or adrenocorticotropin (ACTH), collectively called steroids.  For patients who continue to worsen with severe relapses despite treatment with high doses of steroids, we often treat with plasma exchange. The decision to treat and how to treat depends on a number of individual circumstances and often the preferences of both the physician and the patient. Many many studies have demonstrated that different formulations of corticosteroids (most commonly methylprednisolone or solumedrol, prednisone or dexamethasone) or ACTH in high doses are effective at speeding up the recovery rate from relapses without significantly affecting the amount of long term recovery that would have occurred without treatment 6 months after the relapse. Some studies have demonstrated other long term benefits of steroid treatments but not an effect on clinical recovery. When treatment is considered it is usually best to initiate treatment within 2 weeks of onset of symptoms, although later treatment may be beneficial as well.

Steroid treatments are often associated with mild side effects, although some people experience quite severe side effects that must be managed by a physician with considerable experience. The potential physical side effects are too numerous to mention but include flushing and a metallic taste in the tongue during IV infusion, increased appetite, weight gain, elevated blood sugar, hypertension and upset stomach.  Psychiatric side effects include insomnia, hyperactivity or even mania with psychosis, depression, and cognitive slowing. Rare side effects include refractory hiccups, pancreatitis, severe bradycardia during IV infusion and avascular necrosis of the hip. All side effects tend to be manageable and short lived.

With this totality of information in mind, here are my personal thoughts on treatment of relapses with steroids.

1.    Mild relapses require either no treatment or relatively low dose oral treatment. I find that those patients who know they tolerate steroids well and want to feel better quickly usually prefer treatment with steroids.

2.    Moderate relapse are those that result in changes on examination and a significant alteration of daily activities but do not result in a significant decline in activities of daily living or require hospitalization. Treatment regimens for moderate relapses include 1000 mg of methylprednisolone IV for 3 days with or without an oral prednisone taper, IM ACTH 80 units for 5 days or high dose oral steroids depending on the circumstances and prior experience. Given the extreme cost of ACTH and the demonstrated benefits of other formulations, this treatment is used far less often than other types of steroids. There are those who believe that ACTH has a unique mechanism of action distinct from its corticosteroid effects but this remains mere speculation in MS despite years of research. Patients who continue to worsen over 2 weeks despite treatment with high dose corticosteroids are usually considered good candidates for plasma exchange

3.    Severe relapses are those that result in significant functional impairment impairing several activities of daily living and often requiring hospitalization. These are usually treated with very high doses of methylprednisolone (1000 to 2000 mg per day for 5 to 7 days) often with a prednisone taper. Failure to respond quickly may require the use of plasma exchange to speed recovery.

Please Note:  The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.  Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition.

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