Here is My Question:
I've been searching for clinical trials for primary progressive MS. Its like pulling teeth to get help for this group. Why? I've been on a slow course of it and I don't want to be in a wheelchair before there is any help.

Answer:
To Find out about Clinical Trials for Primary Progressive MS, go to the clinical trials.gov website and in the search for studies text box type, “Primary Progressive Multiple Sclerosis”.
You can then click on the link to any active study recruiting patients ; this should include contact information to learn more about your eligibility and study sites that may be near to you

Good luck

-Rip Kinkel, MD

Here Is My Question:
My wife has secondary Progressive MS. She also has two children with Down's Syndrome. Could they be the cure? Could the children have been born with spectacular anti-neurological strengths? We propose the hypothesis that despite a propensity in DS for certain autoimmune diseases there is a negative association of DS and MS. Genes located on chromosome 21 may thus confer protection against MS. Candidate genes for protective immunomodulation might include interferon receptor I and II and S100b. Substantiated by further epidemiologic data, the identification of these and other chromosome 21 gene products may provide new hints for the understanding of modulatory genes in the pathogenesis of MS. In more general terms, this negative association also may allow to study basic principles of how certain candidate genes might act on autoimmune disease expression. So why not give blood from my kids to my wife (Type matches)?

Answer:
Thank you for you email and the issues raised. Your thoughts about the effects of genetics on risk of MS have some merit and are intriguing. Indeed, we know that some individuals are genetically engineered to be more resistant to developing MS and more able to repair after MS occurs. While there are no direct connections between the genes found on chromosome 21, the sample sizes in studies may be too small. Unfortunately, transfusions of blood from one individual to another will not convey the genetically engineered properties from that blood. Red blood cells have no DNA and do not replicate. What is needed is an ability for a persons own cells to express protective genes."

Benjamin M. Greenberg, MD, MHS
Director, Transverse Myelitis, Neuromyelitis Optica and Pediatric Demyelinating Disease Programs
Director, Neurosciences Clinical Research Center
UT Southwestern Medical Center
Childrens Medical Center
Dallas, Texas

Here is My Question:
I am a 49 yr old female and have had RRMS for the last 20 yrs. I functioned well during this time with only 3 or 4 exacerbations lasting under three months but still leaving behind remnants of new sensitivities. I had been on no medications during those 19 years. I was prescribed Copaxone for 1 year with increased lesions showing and an eye palsy. The eye palsy resolved but bi-lateral drop foot started to set in shortly after.

Still functioning quit well, I started on Tysabri. After 5 years on Tysabri I began to decline requiring me now to use a cane. I tested positive for the JC Virus and was taken off of Tysabri a year later. I was anticipating going on Lemtrada until I learned it was not going to be approved. I have been on nothing since.

I am in other wise good health; eat organics, take good supplements and am about 15 lbs over weight.

It is now one year after stopping the Tysabri and I have severe spasticity in both legs and am almost ready for the chair, but I continue to fight against accepting it. I am week and cannot pull my self up without difficulty. I can still ride my recumbent bike for 20 minutes or so.

My question is what else can I do other than stretch, take Balcofen , Atavan and others?
My neurologist is good but I would like an outside opinion on upcoming drugs or physical suggestions.

Answer:
Thank you so much for sharing your experience with us. While I do not know the details of your case, I can make some surmises based on your description of events, and hopefully provide you and others in similar circumstances with some useful recommendations

First, the description of your disease course over the past few years is far more consistent with secondary progressive MS than relapsing remitting MS. The onset of progressive disease may have started shortly before you began Tysabri and continued during the interval you were receiving this treatment. I can certainly understand your interest in Lemtrada, but receiving it at this time would require you to travel outside the United states and pay cash. You are a possible candidate for one of the many clinical trials currently recruiting secondary progressive MS patients throughout the world. To find trials that may interest you and may even be recruiting in your geographic area, go to the website, clinicaltrials.gov, and in the search box type, “Secondary Progressive Multiple Sclerosis”. You can scroll down the list that will appear to find clinical trials that may be of interest to you. Click on the link to the trial to find the contact information for the study coordinator.

To be honest, the ideal treatment for patients such as yourself is unclear at this time. We generally separate Secondary progressive patients into early and late categories; early cases tend to be transitioning from a relapsing course to a progressive course with continued, sometimes significant evidence of an ongoing inflammatory response. By “ongoing inflammatory response”, I am referring to continuation of either relapses or rapid progression in the setting of continued gadolinium enhancing lesions on MRI. The majority, but not all of patients in this category are under the age of 50. Many of us recommend aggressive treatment at this stage of the disease with cytotoxic agents such as cyclophosphamide or induction courses of rituximab, both available in the united states, but not specifically approved for MS.

Late Secondary progressive disease usually occurs in patients over the age of 50 with very little evidence of the type of ongoing inflammatory response observed in early transitional cases. This stage of the disease is felt to be primarily a neurodegenerative process, perhaps driven by an innate inflammatory response in the brain. Disease modifying treatments at this stage have not been shown to be beneficial. Some of the clinical trials you will see at the clinicaltrials.gov site are meant for this stage of the disease as well.

With regard to your specific question, the management of spasticity at your stage is a balancing act that requires some skill. While drug treatments such as oral baclofen, tizanidine and benzodiazepines (you mention ativan) may reduce the spasticity and spasms, this is often at the cost of side effects such as sleepiness, dizziness, cognitive blunting, dizziness, dry mouth, constipation and increased weakness as your muscle tone is decreased. The general approach to management involves the following steps:

1. Reduce or eliminate painful or noxious stimuli. This can include an area of skin breakdown or injury, a urinary tract infection, persistent urinary retention or constipation, among many possible causes
2. Use a slow titration of a combination of medications to find the best response with the fewest side effects; the most common drugs to combine are baclofen and tizanidine. If spasticity or spasms remain a problem at night, add a benzodiazepine like diazepam at bedtime but avoid these medications during the day
3. Physical modalities are important and should be used daily to reduce the effects of spasticity. This includes skillful stretching at least twice a day and possible functional electrical stimulation. These are useful modalities that require training by a skilled physical therapist with training in neuroscience; Yoga is also a beneficial physical modality to help reduce spasticity.
4. If there is a specific muscle group causing problems with spasticity, such as the hip adductors or the small flexor muscles of the feet, treatment with botox injections is a great choice
5. Those who spend most of their time in a wheelchair often benefit from an occupational therapy mobility evaluation to ensure that their seating is appropriate to reduce the effects of spasticity. Those no longer walking at all may benefit from a standing frame to obtain an upright posture several times a day
6. Lastly, those with severe spasticity not responding to the above treatments usually benefit from an intrathecal baclofen pump (made by Medtonics). This is a programmable and refillable pump implanted under the skin in the abdomen (about the size of a hockey puck) with a catheter that is tunneled under the skin to deliver liquid baclofen directly to the spinal fluid. This deliver method is very effective and avoids most of the side effects associated with the use of oral baclofen pills.
   

I hope this information helps and good luck.

Rip Kinkel, MD

Here is My Question:
I was told and read that Rebif had a huge problem with people who have mental disorders and can and has caused people to commit suicide. Is this true?

Answer:
The relationship between interferon treatment of MS and depression has been a controversial subject for 20 years. Considered as a class, the Beta Interferons used to treat MS (Avonex, Betaseron, Extavia and Rebif) have been variably associated with a minimal increase in the risk of self reported depression when blinded interferon treated patients are compared to placebo treated patients in clinical trials. There is also very little evidence that interferon treatment of MS patients with current or prior depression worsens depression or causes a recurrence of depression.

David Mohr’s study from many years ago clearly identified current depression as a major cause of interferon discontinuation or poor adherence to therapy; improved adherence to interferon therapy in depressed patients was achieved through early identification and treatment of the depression. To help identify patients at risk for depression, some studies have suggested that people with MS who are younger and with higher levels of disability, particularly women, are more prone to depression.
Suicides have also been reported in interferon treated patients; in fact, there were three suicides in one of the interferon studies involving secondary progressive MS patients. Overall, there does not appear to be an increased risk of suicide, however, in interferon treated patients compared to control treated patients.

Identifying additional factors responsible for depression in people with MS is difficult given the extremely high prevalence of depression in MS. Nearly two thirds of MS patients will experience evidence of depression during the course of their illness; this often occurs early in the course of the illness when the same individuals are often initiating therapies such as interferons. Because of the similarity between early interferon associated side effects (increased fatigue, cognitive blunting, general aches and malaise, disrupted sleep, loss of appetite) and some symptoms of depression, it is important to monitor patients closely for the emergence of depression, particularly during the first 6 months of treatment. I do not avoid interferon use in patients with prior or current depression, but I start treatment for depression before starting interferon in those patients who’s depression is untreated, and monitor the treated patients more closely. Difficulty adhering to therapy is one clue that the patient may have underlying depression. Since this may also affect adherence to other therapies, these individuals should be evaluated for depression or anxiety disorders and, if found, treated with either psychotherapy or antidepressant medications or both.

Rip Kinkel

Q: I am wanting to find someone in my area to help me with my cognitive issues. I can't travel to far but I feel like I need a counselor that understands this and that could help me get my life some what back...my depression is still bad. I am also going through a divorce and have been out of a job for over a year and I feel lost. Please advise.

A: From the comments we receive, you are not alone.  Finding a good counselor can be challenging, and when someone is depressed, the process of seeking out help can be overwhelming.  Some resources to help you with this are as follows:

http://www.healthcarejourney.com/depression-and-anxiety.html

http://www.helppro.com/HP/Common/SearchResults.aspx

http://therapists.psychologytoday.com/rms/state/Washington.html

http://www.nationalmssociety.org/Treating-MS/Find-an-MS-Care-Provider/Partners-in-MS-Care

You can also call the local NMSS in your area to ask if they could recommend anyone. The greater northwest chapter's number is Toll Free: 1-800-344-4867

In addition to using the resources above, we encourage you to contact your physician's office or the closest MS Clinic to seek out some names of counselors or psychiatrists that might be able to help you. It is so good that you are reaching out for some help.  Keep that up until you find someone to help you.

Hope this helps. Best of luck.

Q:
I heard from someone that there is a MS clinic at U of M with all the doctors you need in one place. How do I get the number to be able to make an appointment, if there is such a clinic.

A:
We are assuming that you mean the University of Michigan? If not, please write back and let us know which U of M you mean (Mississippi, Missouri, Minnesota, Miami, etc.) The Multiple Sclerosis Center, part of the University of Michigan’s Department of Neurology, does have a team of physicians to address your MS.

Here is the link http://www.uofmhealth.org/medical-services/multiple-sclerosis, and their number is 734-936-6727.  Good luck!

Augusto Miravalle, MD is a board certified neurologist who sub-specializes in Multiple Sclerosis and related neuro-immunological disorders of the brain and spinal cord. He completed his neurology residency training at Loyola University, Chicago where he served as chief resident in Neurology. He completed a clinical fellowship in MS and related disorders at Beth Israel Deaconess Medical Center, Harvard Medical School. Dr Miravalle has particular interest in gray matter pathology, particularly neocortical volume changes, cortical lesions, and their impact on cognitive and physical disability. He sees patients at the University of Colorado Hospital Anschutz Centers for Advanced Medicine at the Fitzsimons campus. Dr. Miravalle is a member of the University of Colorado Multiple Sclerosis Center. Dr Miravalle’s clinical and research work in MS is complemented by a very active administrative responsibilities in Medical Education, serving as Vice Chair for Education and Residency Program Director for the Department of Neurology, University of Colorado.

We are thrilled to welcome Dr. Miravalle to HealthCare Journey to share his knowledge and expertise with you!

--HealthCare Journey Team

Here is My Question:

I was on Aubiago for ten months and was taken off it, due to severe side effects. I was wondering if it is safe to get pregnant? And I was taking Copaxone which was a month of pain. Is it safe to continue my family?

Answer:

Aubagio (or teriflunomide) is a pregnancy category X medication which means that fetal abnormalities are a real risk (this is based on information from a similar medication called leflunomide).  Data presented at the American Academy of Neurology this year indicated 83 reported pregnancies among women exposed to Aubagio.  Among these 83 exposures, 70 were exposed up to week 11 of pregnancy with 26 live births demonstrating no structural or functional abnormality.  Among the rest, 29 patients elected for an induced abortion and 13 had a spontaneous miscarriage (and 2 were unaccounted for).

Family planning is an issue for patients who decide to start Aubagio.  If you are contemplating pregnancy, I would make sure to check a teriflunomide level (blood lab) to ensure that it is adequately out of your system.  Usually, coming off Aubagio means undergoing an “elimination protocol” using a medication called cholestyramine for 11 days.  We do this because Aubagio tends to remain in the body for quite a long time (up to 2 years after the last dose if you don’t do the elimination protocol).  The elimination protocol usually accelerates the removal of Aubagio, but occasionally a second round of cholestyramine is needed.  Before attempting pregnancy, I’d recommend ensuring it is completely out of your system.

Copaxone is a pregnancy category B medication, and should not be a contraindication to pursue pregnancy (as you have been off of it for a while).

I would encourage you to discuss this with your MS provider as there can be other considerations to take into account when planning for pregnancy with MS.  For the average patient, pregnancy has a good effect on MS, and may be on par with many of our disease modifying therapies (especially during the third trimester).  Good luck!

-ASN

Here is My Question:
I gave birth to two children with Down Syndrome. I also have secondary Progressive MS. Can this be related?

Answer:
There is not a relationship between MS and Down syndrome. However, there can be a change in risk in woman who have had chemotherapy.

Benjamin M. Greenberg, MD, MHS
Director, Transverse Myelitis and Neuromyelitis Optica Program and Pediatric Demyelinating Disease Program
Director, Neurosciences Clinical Research Center
Department of Neurology and Neurotherapeutics
Department of Pediatrics
UT Southwestern
214-645-0555

Here is My Question:
I was diagnosed with MS (lesions on brain MRI) in Feb 2014. I had a Lumbar Puncture. Since that time I have a very uncomfortable feeling at the base of my neck in the center or the top of my spine (I think) that feels like pressure. It even get painful at times. What can I do, without medicine to relieve that feeling that won't cause damage to my spine?

Answer:
Your symptom is not one I can diagnose over a blog, but requires a face-to-face visit with your doctor.  Occasionally, an unusual headache can occur after a spinal tap that is only present when sitting or standing up, but goes away when you lay down.  This pain can be reflected in the neck as well.  Usually this is self-limited and goes away on its own.  Your symptoms sound different and require a formal evaluation in clinic.  Once the cause is suspected/known, then your doctors can offer a course of therapy.
-ASN

Q. Will there be a solution to urinary incontinence because the medicine I was on is on back order. I can not control it on a regular basis.

A. We have received quite a few questions regarding urinary incontinence. Here is some information to answer your question:

http://www.healthcarejourney.com/physician-blog/the-idiots-guide-to-urination-and-ms

http://www.healthcarejourney.com/q--a-for-virtual-ms-center/ways-to-reduce-frequent-urination-for-people-with-multiple-sclerosis

Q:  I was admitted to the hospital with symptoms...had a CT scan positive result for MS but was then told that my MRI showed no MS. I am still suffering symptoms. I never had a spinal tap to confirm. Could I still have MS? I have had bladder incontinence for months, bowel problems, and now suffer left leg muscle weakness. I was put on steroids that eased symptoms but am still suffering weakness, tingling hands, feet, and face. Please help looking for answers.

A:  Establishing a diagnosis for neurological problems is complicated; at a minimum it requires the skillful elucidation of your history, a detailed examination and correct interpretation of your diagnostic evaluation. Some of the statements is your question suggest at a minimum either misinterpretation of your diagnostic evaluation or failure of the doctors to clearly explain their findings to you. I would strongly suggest another opinion if your current doctors have not been able to either provide you with a diagnosis or give you an adequate explanation for your symptoms. It would be difficult if not impossible for me or any doctor to provide any further help without seeing you.

I don't know where you live, but there are excellent clinics across the country with physicians who specialize in MS.  You can use a listing from the NMSS website as a starting point to find an MS clinic in your area...CLICK HERE.  This link allows you to enter your zip code and click on "Centers for Comprehensive MS Care." If you let us know where you live, we might also be able to provide some guidance.

I also suggest reading the links below in preparation for getting a second opinion:

http://www.healthcarejourney.com/physician-blog/the-diagnosis-of-multiple-sclerosis-ms

http://www.healthcarejourney.com/physician-blog/how-to-prepare-for-a-visit-to-your-ms-specialist-the-present-and-the-future

Good luck

-Rip Kinkel, MD

Here is My Question:
I've been off Tysabri for 11 months and I still feel badly. I've had 2 relapses and 3 infections. I don't know what to do.

Answer:
I would recommend discussing the possibility of restarting Tysabri with your MS doctor. If your doctor is opposed to restarting Tysabri, ask him/her for specific reasons. If you are not satisfied with his/her answers, ask for another opinion with an MS specialist who is more comfortable with alternative dosing regimens and monitoring protocols for patients on long term Tysabri treatment. Some doctors are uncomfortable with continuing Tysabri in any patient who is JC virus antibody positive regardless of the antibody index or other risk factors. While I respect their point of view,  I feel that patients should be offered the option of continuing treatment under a different physician if the patient is competent to make decisions and is aware of the risks involved.

Good Luck

-Rip Kinkel

Here is My Question:
After years on Tysabri, my JCV was higher than was considered safe so I switched to another med. Does that JCV level go down over time? Does is stay at that high(er) level?

Answer:
There is no evidence at present that the amount of JCV antibodies (i.e. the JCV antibody index value) when you are tested is related to being on or off treatment with Tysabri. JCV antibody index values will fluctuate over time and can either go up or drop to undetectable levels ( i.e a Negative JCV antibody result in a person previously positive).  Generally, index values tend to stay within a certain range, either negative or low (< 1.5) or high (> 1.5) with repeat testing; but this is not always the case and requires continuous monitoring while on treatment.

The important thing to remember is that we have no knowledge of a person developing PML more than 6 months after stopping Tysabri, regardless of JCV antibody index values or treatments used after stopping Tysabri.

Rip Kinkel, MD

Q: On the neurology congress in Philadelphia in 2014 there was a topic about neuroplasticity and PPMS.

http://conferencecenter.msworld.org/american-academy-of-neurology-2014/day-three-at-aan/study-on-therapy-for-progressive-multiple-sclerosis

Did they continue to find the influence of neuroplasticity on PPMS patients?

A: There were many exciting findings related to MS research shared at the American Academy of Neurology in May 2014.  Of great interest to many were reports specifically related to treatment for people with progressive MS (PMS).  Dr. Gary Cutter, Professor of Biostatistics at the University of Alabama, briefly spoke about preliminary findings related to  non-pharmacologic therapy for improvements in the arm and hand, as well as legs, in people with PMS. 

In this study, Dr. Victor Mark and colleagues examined the effects of a rehabilitation strategy called “constraint-induced movement therapy”.  This approach has been studied most extensively in people with paralysis or weakness due to stroke.  Constraint-induced therapy involves constraining, or tying down, the less affected arm or leg to force the affected (paralyzed or weak) arm or leg to work for a certain period of time.  The idea is that the more affected limb is limited in function in part because the individual has learned to not use that limb, therefore causing it to get worse.  In constraint-induced therapy, restricting activity to the more affected limb forces the nervous system to work to restructure itself and restore function in the pathways that cause movement.  In other words, by using this approach of forcing the affected limb to work, this is causing neuroplasticity in this system, and hopefully restoring function.

Five people (study participants) with either primary or secondary PMS were treated with constraint-induced therapy with direct supervision of a therapist 3 hours per week for 2 to 10 consecutive weeks (a total of 30 hours of therapy).  Study participants performed repetitive tasks that were functionally relevant to them, such as stacking cups or turning items, and tasks were increased in difficulty by the study therapist as the participant demonstrated improvements in performing the tasks.  Participants also wore a padded mitt on the constrained limb for a target of 90% of waking hours on training days.  The investigators measured arm function before and after the 30 hours of treatment.  They also redid the measures 4 weeks after the last therapy session.

Participants demonstrated an improvement in their movement activity log, which measured their real life use of their arm and hand.  They also reported a decrease in fatigue with use of their arm and hand.

It is important to note that there were no measures of what was happening in the nervous system.  For instance, there were no measures of brain or spinal cord activity before and after the therapy.  Thus, it is not clear if changes in function were matched by changes in the nervous system, and due to neuroplasticity.

It is also important to note, and specifically as it relates to this question, that the changes that they saw were still there at 4 weeks post-treatment.  However, they were not measured again and it is therefore not clear if the changes last much longer than that.  Further study is required to determine how long these changes will persist in people with PMS

Finally, this study had only 5 participants, and a larger study is important to see how much these findings can be generalized to the larger population of people with PMS.  However, it is particularly exciting that some people with primary and secondary PMS were able to demonstrate improvements in function.  This challenges the traditional dogma that people with moderate to severe MS cannot benefit from rehabilitation. 

-Deborah Backus, PT, PhD, Shepherd Center

Reference:

Mark, V. W., Taub, E., Bashir, K., Uswatte, G., Delgado, A., Bowman, M. H., ... & Cutter, G. R. (2008). Constraint-Induced Movement therapy can improve hemiparetic progressive multiple sclerosis. Preliminary findings. Multiple Sclerosis.

Here is My Question:
What are the options for someone with primary progressive MS? I am 66 and was diagnosed after a spinal tap in 2008; am physically active (downhill ski, but less aggressively and at my own pace); have no visual changes due to MS; have some areas of cognitive impairment (mild) but other areas are very superior. My neurologist says that there is no treatment and the neuro-psychologist said to do activities like crossword puzzles or study a foreign language. I am satisfied with my physical status, but would like to limit my cognitive decline as much as I can.

Answer:
Please see Dr. Kinkel's excellent blog post on cognition and MS (posted 7/22/2014) READ MORE

In addition, I would add that as we age, all can succumb to common problems that affect cognition.  In this case, we can't assume that cognitive problems are solely due to MS (if at all).  Your neurologist can help screen for other causes of cognitive dysfunction with the help of a neuropsychologist (which it appears you have already met).  

What we have learned is that medical conditions that can affect blood vessels (ie, "vascular disease") such as high blood pressure, high cholesterol, blood sugar regulation problems, smoking, etc can encourage disease progression and affect cognition and also cause "little white dots" on the brain scan as well.  These problems are more prevalent as we age.  Moreover, the litany of other ailments that Dr. Kinkel lists in his blog post which contribute to cognitive problems are also more common as we age and should be taken into consideration when trying to tease apart potential reasons for your symptoms.

I do not have much more to add to what you are doing or what has been said in the aforementioned blog post.  I would just emphasize the need to remain physically healthy to try and mitigate the other potential causes of cognitive difficulty.  Specifically, work on aerobic exercise (with a goal of 30 minutes of continuous exercise a day, for 5 days a week), a balanced/healthy diet, and adequate and restorative sleep.  Of course, consult with your doctors about the type and intensity of aerobic exercise that is appropriate for you.

I would also add one last thing...Dr. Kinkel suggests in his blog that our disease modifying therapies very well may mitigate cognitive dysfunction over time.  I agree.  I would also point out that our approach to treatment of MS is shifting.  The term "primary progressive MS" is becoming a relic with alternative terms such as "active and/or progressive" as descriptors to a patient's MS activity.  Reason for this is that even the "primary progressive" patients can have inflammatory disease activity (even if not recognized clinically or symptomatically) noted on the MRI scans.  If this is the case, even a patient with the label of "primary progressive MS" could qualify for a disease modifying therapy because they are demonstrating "active" or "inflammatory" disease activity that likely will respond to an MS therapy (and could impact cognitive decline).  I'm am not advocating for frequent/routine MRI scanning of progressive MS patients, but under the right circumstances (ie, worsening cognition), it should be considered.

-ASN