Ask the Doctor
Questions for Our Readers
By Dr. Barry A. Hendin
MSAA’s Chief Medical Officer
Q: MSAA recently featured the cover story, “In Search of MS Biomarkers,” in its Summer/Fall 2025 issue of The Motivator. In the article, you note that in MS, biomarkers are either found via imaging or via bodily fluids, including blood or cerebrospinal fluid. I wanted to ask how often most neurologists might be looking at such biomarkers and if testing of bodily fluids is done routinely, or if much of this has yet to become a part of day-to-day practice per the changes as noted in the recent update?
A: As you point out, biomarkers include MRI imaging, and humeral biomarkers, derived from bodily fluids, such as blood and spinal fluid.
MRIs are our most frequently used biomarker for risks of acute inflammation and MS progression. More sophisticated MRI techniques are now being employed to predict prognosis for MS progression.
Currently, the most commonly used humeral biomarkers are spinal fluid oligoclonal bands for MS diagnosis. Other biomarkers include aquaporin-4 antibodies for the diagnosis of NMOSD (neuromyelitis optica spectrum disorder), and MOG (myelin oligodendrocyte glycoprotein) antibodies for MOGAD (myelin oligodendrocyte glycoprotein antibody-associated disease) diagnosis. Both NMOSD and MOGAD are autoimmune disorders of the central nervous system that may mimic multiple sclerosis, but are separate diseases.
The two most commonly used serum-derived humeral biomarkers are neuro filament light and GFAP (glial fibrillary acidic protein). Neuro filament light is a marker for acute inflammation such as a relapse, while GFAP has been a marker for MS progression. An 18-protein array, which measures the proteins’ biochemical activities, has been developed by Octave with the hopes of serving as a marker for acute inflammation and progression.
These biomarkers are evolving. Some clinicians are using them as part of regular practice, and some neurologists are not using them regularly. There is an active research program to assess their best role and usage in clinical practice. Stay tuned!
Q: I am a 75-year-old female retired nurse anesthetist and was diagnosed with MS in 2001 at the age of 51. I’ve been taking a disease-modifying therapy, but my neurologist has diagnosed me with “smoldering MS” and feels that I should not take any disease-modifying therapy due to my advanced age.
Not knowing if I had aged out of treatment, we agreed to follow my B cells, and when they rose above zero, treatment would be resumed. My treatment schedule is now every nine months.
Do you agree with this treatment plan or do you indeed feel that someone my age does not benefit from further treatment? Is my immune system so dampened by my age that any progression would be minimal?
A: A choice regarding when to stop disease-modifying therapies (DMTs) is always going to be a shared decision between you and your clinician. But there are biological facts and guiding principles that may help with that decision-making.
The guiding principle for stopping or starting disease-modifying therapies is based on the ratio between the potential risk and the benefit of that treatment. The benefit should always exceed the risk.
The biology of aging includes immuno-senescence, which refers to the natural aging of the immune system. Immunosenescence reduces the power of autoimmunity and therefore the likelihood of relapses as people with MS age. Our DMTs exert their greatest power by reducing relapses. And if the risk of relapse is less than the power or benefit of the DMT, treatment becomes less necessary. The benefit therefore is less. As we age, the risk of our immunotherapies remains the same or increases. Therefore, the risk benefit ratio changes. We know that in different populations, this shift can begin as early as a person’s 50s or 60s.
For the clinician and for the person with MS, assessing risk in an individual is more difficult. We can use biomarkers such as MRI and humeral biomarkers (please see earlier discussion of biomarkers on page 22). Despite our improvement in technology, there remains uncertainty regarding any individual patient. In clinical practice, there is a wide variation as to when the discussion begins and the outcome of those discussions with regard to stopping medications. Some clinicians and some patients choose to stop earlier and some wait longer, but as I said at the beginning of this answer, it’s ultimately a decision between the patient and the clinician.
In my own practice, we have these discussions as my patients age. I encourage considering the discontinuation of DMTs as people progressively age, particularly in their late 60s and 70s. Not surprisingly, some of my patients discontinue in their 50s, while others choose to wait and delay discontinuation until they are older.
Q: I am experiencing overwhelming fatigue, and I know that many people with MS suffer from this symptom. I am trying to plan ahead, avoid overheating, and conserve my energy. Do you have any other specific recommendations, and are any specific medications for fatigue safe and effective?
A: You are correct that many people with multiple sclerosis suffer from fatigue – it is probably the most common symptom of MS.
Your strategy for dealing with fatigue is also basically correct. It’s a combination of conserving energy and also of using energy as efficiently as possible.
My general recommendations center around wellness. We want to make sure that people with MS are getting sufficient sleep, exercising regularly (but not beyond what can be comfortably tolerated), and eating a healthy diet, such as a Mediterranean diet.
We want to make sure that they are attending to their mental health and particularly any associated anxiety and depression. Anxiety and depression increase fatigue, so it’s reassuring to know that these mental health issues are treatable by the appropriate mental health specialist, and often with medications. It’s helpful to have a good primary care physician to monitor any comorbidities (other conditions), because medical problems often affect energy and fatigue.
Using your available energy efficiently is important. That means setting priorities for the activities that are the most important to you, and taking breaks when necessary, i.e., listening to your body. Because people with MS are so often sensitive to overheating, we encourage strategies to avoid overheating, which include a few different strategies, such as drinking a cold or frozen (non-alcoholic) drink, taking a cool shower, and the use of cooling products. For people with mobility issues, we encourage using assistive equipment to allow for more efficient mobility. Please note that MSAA offers free cooling products plus safety and mobility equipment to individuals meeting financial eligibility requirements.
Most people can manage fatigue with a combination of behavioral and wellness strategies, but sometimes medications are helpful. Although there are currently no FDA-approved medications specifically for MS fatigue, amantadine (previously Symmetrel®) and Provigil® (modafinil) are widely used off-label to treat MS fatigue. The good news is that there are multiple strategies for dealing with the fatigue of MS.
Barry A. Hendin, MD, is a highly accomplished neurologist who specializes in MS. He is the chief medical officer for the Multiple Sclerosis Association of America (MSAA) and has spoken at several of MSAA’s educational programs. After 45 years as a neurologist with Phoenix Neurological Associates, Ltd., Dr. Hendin is now director of the Arizona Integrated Neurology MS Center. He is also director of the Multiple Sclerosis Clinic at Banner University Medical Center and clinical professor of neurology at the University of Arizona Medical School.
Please email your “Ask the Doctor” questions to askdr@mymsaa.org