Here is My Question:
Ocrevus vs. Avonex? I'm a 62 yr. old female who has taken Avonex for over 20 years. Because of MILD spinal progression and brain atrophy as evidenced between a 2013 MRI and a 2017 MRI, my neurologist wants me to switch to Ocrevus.

My November 2017 MRI shows no active demylenation and I have no clinical symptoms or disability and haven't had any lesions since one showed inactive on my brainstem on the 2013 MRI. My last symptoms of any kind were in 2005- slight arm weakness for a day or so. There's no way to know when the progress began; 2014,2015 etc.?

I'm really concerned about the Ocrevus side effects - PML (I haven't been tested for JC virus yet), upper respiratory infections, cancer, hair loss etc. vs. Avonex side effects.

So my questions are:
Is Ocrevus really that much better than Avonex in stopping the spinal and brain atrophy? 
What really warrants a medication change?
Does mild progression mean a DMT has stopped working?

I'm considering stopping all DMTs at this point. Would appreciate any thoughts. 

Answer:
It is very difficult to answer your question; some of the information you provide is inconsistent; Please clarify the following and I will try to help. The questions I can answer are at the bottom:

1. You mention, “mild spinal progression” and then state that you have experienced no "clinical symptoms or disability” or  new MRI lesions since 2013. If this is the case what makes you or your doctor think there is “mild spinal cord progression” ? Is this statement based only on MRI changes in the spinal cord and, if so, what kind of changes occurred.  It is hard to imagine a person with MS with no new MRI lesions, no symptoms and no disability over a 4 year period (2013 to 2017) who has experienced significant progression of their disease based on qualitative atrophy measures

2. How was the brain atrophy between 2013 and 2017 measured? If this was not done correctly many mistakes can be made. Remember, a healthy person in your age group will experience a decrease in whole brain volume of up to 0.2 % per year (0.8 % over 4 years). This degree of atrophy can be larger in certain regions of the brain. If your doctor’s impression of increased atrophy over 4 years was based solely on qualitative eye-balling your films (and not done with an automated image analysis technique) , then the results are not very accurate of useful.

As for your other questions

1. Ocrelizumab (Ocrevus) like Rituximab is estimated to have a very low risk of PML (less than 1 in 25,000). 
2. JCV antibody status will have nothing to do with risk of PML on Ocrelizumab. As we have discussed many times on this site, JCV index is only associated with risk of PML when treated with Tysabri.
3. Mild clinical progression in your age group could simply be a result of the combined effects of damage from prior MS activity  and normal aging
4. Generally speaking, a DMT change is warranted by new disease activity, defined as new MRI lesions or relapses, or a rapid progression rate
5. If there was a good reason to start a DMT, then there probably is a good reason to continue it. I do not know enough about your case to tell you if there was a good reason for you to start a DMT
6. Stopping a DMT is usually only recommended in people who should not have been placed on a DMT to begin with or in a person (generally over 60 or 65) with fairly longstanding progressive MS with no recent history of disease activity  defined as relapses or new MRI activity

Hope this information helps.

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

Here is My Question:
What are the risks and benefits of rituximab vs Ocrevus?

Answer:
Both rituximab and Ocrelizumab bind to circulating CD20 B Cells and destroy them. Although they bind to different portions of the CD20 protein on the surface of the B cells, the end result of this binding is identical. 


Rituximab is a Chimeric antibody; this means it is a fusion protein containing both human and mouse protein components. Because your immune system may view the mouse protein as foreign, it is possible for people to develop human anti-chimeric antibodies (HACA). In the phase II HERMES trial of rituximab for relapsing MS, approximately 25 % of treated patients developed HACA, but there was no relationship between the development of HACA and either treatment efficacy or infusion related reactions (IRR). Nevertheless, there are case reports of patients with other conditions (i.e. rheumatoid arthritis or SLE) losing benefit from Rituximab after the development of HACA, and some believe that HACA can lead to persistent, more severe IRRs with subsequent infusions. This issue is controversial since IRRs are very common in all patients administered either rituximab or orelizumab (see below), a humanized anti-CD20 monoclonal antibody that does not lead to the development of HACA.

Ocrelizumab is one of the currently approved entire human anti-CD20 monoclonal antibodies. Human anti human antibodies (HAHA) develop in very few individuals and do not seem to be related to be related to efficacy or infusion related reactions (IRR). Ocrelizumab is also associated with a high rate of infusion related reactions.

Other humanized anti-CD20 monoclonal antibodies include obinutuzumab, eltuzumab, and the fully human, ofatumumab. None are currently approved for multiple sclerosis but this is likely to occur in the future.

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

Here is My Question:
Hi my son is 17 and has recently been diagnosed with relapsing remitting MS. He is JC negative. His Neurologist has offered him the choice of Tysabri or Ocrevus. Cost is not a factor as both are covered by the PBS in Australia which means they are available at very minimal cost.

We are finding it very difficult to work out which one to start with. So far he has not had any steroid treatment. He does have a spinal lesion. What are your thoughts? Thanks

Answer:
This is a great question and one for which there is no right answer. On one hand the Tysabri is a monthly infusion while Ocrevus is twice a year. On the other hand, Ocrevus is more immunosuppressive than Tysabri. In general, for new starts in the US, more patients are starting with Tysabri than Ocrevus, but this may change over time as more data becomes available. The efficacy data for both is great, but there is more long term safety data with Tysabri. In the end, whichever one is chosen, careful monitoring is indicated to ensure an adequate response to the medication.

Benjamin M. Greenberg, MD, MHS
Vice Chair of Translational Research and Strategic Initiatives
Cain Denius Scholar of Mobility Disorders
Distinguished Teaching Professor
Department of Neurology and Neurotherapeutics
Department of Pediatrics
UT Southwestern Medical Center
Dallas, Texas

Here is My Question:
Is there an alternative MRI contrast to Gadolinium? I understand it leaves metal deposits in the body's organs and tissues including the brain.

Answer:
Gadolinium is a paramagnetic ion used as a contrast agent in MR imaging. Gadolinium is toxic, so it must be administered as a chelated molecule. There are many gadolinium contrast products on the market in the united states and Europe. They differ primarily in the type of chelates used and the stability of the chelated molecule. Macrocyclic chelates are the most stable and least toxic of the products on the market, particularly in individuals with kidney disease. Recent guidelines recommend using these macrocyclic chelated gadolinium contrast agents in people with kidney disease. They also recommend using the lowest dose required, since higher doses are associated with greater toxicity.

Currently, the least toxic gadolinium contrast agents (all macrocyclic chelates of gadolinium) are Prohance (gadoteridol), Dotarem (Gadoteric acid) and Gadavist (Gadobutrol).

This being said, we still do not know if certain gadolinium contrast agents accumulate more or less in our body tissues- including the brain- more than other agents. We also do not know the consequences of this gadolinium accumulation. 

Therefore, it is generally recommended that doctors use gadolinium contrast agents  only when needed and in the lowest dose required. Newer automated image analysis techniques are decreasing the requirement for gadolinium contrast in monitoring scans done in people with MS. 

It is also recommended that if MRI contrast is needed in a patient with kidney disease, the macrocyclic chelated agents mentioned above should be used in the lowest dose required.

There are several non gadolinium based contrast agents in development but none have been approved as of this writing.

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

Here is My Question:
Why do my fingers prune in cold when I'm outside, like I have been in bathtub all day? Why do they sometimes turn white?

Answer:
What you are describing is commonly referred to as Raynaud’s phenomenon.  Usually it isn’t related to anything and is not serious, but sometimes can be a sign of autoimmunity (which is evaluated by a rheumatologist).  This is not a secondary manifestation of MS.

A. Scott Nielsen MD MMSc
Neurologist and MS Specialist at Kaiser Permanente

Here is My Question:
For a relapse (new activity as seen by T2 hyperintensities on MRI), I know that IV steroids lessen the symptom load and duration. 

But I'm less clear on whether there are possible benefits from the steroids to the actual healing of the lesions themselves. I've heard yes and no. 

Can you help clear this up?

Answer:
Steroids shorten the duration of relapses and help speed up the recovery process. Prior studies failed to show a benefit on the degree of relapse recovery after 3 to 6 months. In other words if you wait long enough, the degree of clinical recovery is the same whether treated with steroids or untreated.

​However, many of the older studies are likely biased by the exclusion of people with more severe relapses. What I mean is that people with more severe relapses will tend to decline consent to enter a study so they can receive steroids without the risk of receiving a placebo or less active treatment. I suspect there are long term benefits of steroids in patients with severe relapses particularly if received within 2 weeks of onset. There is also evidence that MRI lesions responsible for relapses show less permanent long term damage in individuals treated with steroids.

This is why we tend to recommend steroids in people with moderate to severe relapses and often avoid steroids in people with mild, usually sensory relapses.

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

Here is My Question:
Why are my palms always hot during sunny days? it is so annoying that I have a lack of concentration and blurry vision.

Answer:
Your extremities, particular your hands, and your head represent large surface areas for dissipation of heat and maintenance of normal body temperature, particularly on hot sunny days.

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

Here is My Question:
I have been getting brain MRI for 2 years. My symptoms are buzzing sensations in my left leg and pins and needles in my left foot every now and then. My vision got blurry so I've seen the eye specialist multiple times but he said my eyes are perfect. 

Clinical History: Intermittent buzzing left upper limb and lower limb 
(independently). Brisk knee jerk. Otherwise normal examination. For exclusion 
of demyelination. 

Cranial MRI results:
There is no cerebral mass lesion identified. No cerebral cortical signal abnormality identified. There are several foci of high signal intensity again seen within the cerebral white matter. There has been no increase in number when compared with the previous MRI dated 11/11/2017. There are no specific 
features. There is no lesion within the corpus callosum. Cerebral deep grey nuclei are unremarkable. No focus of cerebral diffusion restriction is seen. No surface collection is seen over the cerebral convexity. No lesion seen within the brainstem or cerebellum. No hydrocephalus. Intracranial arterial and cerebral venous sinus flow voids are unremarkable.

So my question is my neurologist said my brain MRI is fine and he doesn't think I have MS but has now booked me in for a lumber puncture. I don’t know what to do I’m so scared of getting a lumbar puncture should I go ahead even though my MRI is fine ? Please help :)

Answer:
Lumbar punctures are safe and well tolerated as long as there is no mass lesion in the brain, no blockage in the spine and when done using either an atraumatic needle (no bigger than 22 gauge) or a small bore (25 gauge) regular needle.

It sounds as though you are the perfect candidate for a lumbar puncture based on the history you provided. As long as the procedure is done with the type of needles described above, there is a very low risk of headache after the procedure and little discomfort during the procedure.

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

Here is My Question:
I was just diagnosed with MS. I've been taking Tecfidera for 6 months and had another MRI and had new lesions. What drug do you suggest? 

Answer:
All therapies are partially effective, and some have proven to be better than others in head to head clinical trials. Because they are partially effective, interval disease activity on the MRI (particularly after a short time on medication before the drug exerts it’s full effect) may not prove the therapy is ineffective or the wrong choice for a given patient situation.  There are so many factors to therapy choice and monitoring that I can’t answer your question without evaluating you myself.

I’d suggest meeting with your neurologist and discussing your questions and concerns. Before embarking on a therapy, there should be an understanding and agreement regarding what an adequate response is to the therapy and benchmarks to determine when a therapy is a failure and what the contingency plan is for you.

A. Scott Nielsen, MD MMSc
Neurologist and MS Specialist at Kaiser Permanente

Here is My Question:
I am newly diagnosed. I am 52 yrs old and have a cataract which needs removal and a lens implanted. I'm pretty sure this is a problem I have had for about 10 years (undiagnosed). Is this connected to MS at all?

Answer:
Cataracts are not due to multiple sclerosis. They occur mostly commonly as our eyes get older. Sometimes they can be the result of long-term exposure to steroids (with which some patients with MS are treated.

Benjamin Osborne, MD
Associate Professor of Neurology and Ophthalmology
Director, Neuromyelitis Optica (NMO) Clinic
Director, Neuro-Ophthalmology Clinic
Associate Director of the NIH/Georgetown Neurology Residency Program
Medstar Georgetown University Hospital
3800 Reservoir Road, NW 7PHC
Washington, DC 20007

Here is My Question:
Can I take cortisone pills while on Tecfidera?

Answer:
Cortisone (a steroid pill) pills may be taken with Tecfidera. However, long term, combined treatment of steroids (Cortisone, prednisone, methylprednisolone or dexamethasone to name just a few types of steroids) with Tecfidera may increase your risk of infections, which may be serious.

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

Here is My Question:
I have lesions on my brain, they were found 5 years ago. Not diagnosed. I was at the neurologist because of bad stenosis in my neck and trying to treat the symptoms which is shoulder, arm and back pain. Back pain since 1988. Now my legs are extremely weak and heavy by days end and do tingle when I get into bed. My lesions have not changed, so does this mean it is not MS? Are the lesions there just by chance? I am having an MRI done on my lumbar next week, not sure why he is not doing the entire spine when my legs are heavy and weak and also the fact that 8 years ago after giving birth my body was in pain for 10 months and even had to scoot down the stairs each day. Two questions please. 1. Will lesions show on a lumbar MRI? 2. Can the lesions mean nothing? 


Answer:
MRI scans do not show “Lesions”.  The word, “lesion” is more appropriately used to refer to the visible pathological or microscopic appearance of tissue in the brain or elsewhere. 

MRI scans do show "T2 hyperintensities", which are white appearing spots observed on certain imaging sequences. T2 hyperintensities may mean nothing or may mean a person has multiple sclerosis or some other disorder. Determining the significance of white spots on an MRI depends on the history and examination findings as well as the specific appearance of the white spots.

These white spots on MRI can be seen anywhere in the brain or spinal cord. An MRI of the lumbar spine will only look at the very lowest part of the spinal cord and is not the best way to look for MS in the spinal cord.

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