Question:
Please please help me. I have MS and am not on any trials for MS just on an antidepressant and Valium. I have profuse hair loss and have tried many products but have had no luck. I am wearing a wig now. Can you suggest help for me as am at my wits end and am very depressed.
​

​Answer:
Hair loss is not something that is related to MS directly. We usually send patients to a dermatologist to look for the root cause. There are some other autoimmune conditions that can lead to this, but a dermatologist can help sort it out efficiently.

Benjamin M. Greenberg, MD, MHS
Vice Chair of Translational Research and Ambulatory Care
Department of Neurology and Neurotherapeutics
Director, Transverse Myelitis, Neuromyelitis Optica Programs
Co-Director, Pediatric CONQUER Program
UT Southwestern Medical Center
Childrens Health
Dallas, Texas

Here is My Question:
Why is my CD4 CD* blood test low?

Answer:
The CD4 cell is a type of white blood cell (called the helper T cell) which serves many functions including viral immunity.  The count is low in the MS patient due to medication to treat the disease.  Common medications that can do this include our immunosuppressant medications (i.e., Tecfidera and gilenya for instance).  Certain infections, bone marrow disease, etc can also cause low counts.  Your specific counts should be interpreted by your physician.

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

Here is My Question:
How frequently are patients diagnosed with MS or suspected of having MS but not started on disease modifying therapy (DMT) and what are the criteria for starting DMTs in the absence of certain diagnosis? What makes a neurologist prescribe DMTs? What makes a neurologist not prescribe DMTs but suspect MS over several years?

Answer:
Here are my thoughts to your questions:
​
1.  How frequently are patients diagnosed with MS or suspected of having MS but not started on DMTs and what are the criteria for starting DMTs in the absence of certain diagnosis?  Answer:  first off, patients should have a diagnosis of MS or CIS (clinically isolated syndrome) before discussing the appropriate use of DMTs (disease modifying therapies).  Part of the criteria of diagnosing MS is to rule out alternative explanations for the patient’s presentation.  If that has been reasonably done, the DMT discussion is appropriate.  My practice has been to offer a DMT for any patient with confirmed multiple sclerosis (per the 2010 McDonald Criteria) that has reasonable evidence that they are in the “inflammatory phase” of their MS (since this phase is where the DMTs exert their effect).  Evidence for the inflammatory phase includes hx of semi-recent relapse (of concern for this), and MRI evidence of contrast enhancing lesions or interval development of T2 hyper intensities (these are the white spots on the brain scan).  When confirmed MS is present, in my opinion, it is best to treat as we do not have a reparative therapy at present, only therapies that mitigate future inflammation.  Cases where I may hold off on DMTs but simply monitor carefully are the CIS cases where they have very little to no MRI lesions.  For instance, follow-up reports from the optic neuritis treatment trial demonstrated that the more brain lesion that are present on the initial scan, the higher the risk for development of MS.  Conversely, having very low lesion burden on the initial MRI suggests a ~25% chance of developing MS over the next 10 to 15 years.  Those patients, in my opinion, may be best served by monitoring them clinically and with MRI and starting DMT only if they prove to have evidence of persistent inflammatory activity.  The “uncertain diagnosis” that you refer to would include the CIS cases and patients who I strongly suspect they have MS and an exhaustive evaluation of mimicker diagnoses are negative.

2.  What makes a neurologist prescribe DMTs?  Answer:  I suspect you may get slightly different answers to this question, however, I err on the side of treatment for the reasons I detailed above.  It is noteworthy to point out that the very first approved DMT, betaseron, has published 21 year data on disability long-term.  We learned that those who start betaseron early (rather than waiting) had significantly less disability (in the case of this report, mortality) compared to those who had a delay in start of approximately 2 years.  Although I don’t have data for my next point, I do have my personal experience following MS patients since 2001 (at a time where we have a few therapies, and at that point, for only a few years).  I suspect that most, if not all, of our DMTs would show similar findings as that follow-up betaseron study.  The reason I believe so is my anecdotal experience of seeing a much higher proportion of patients in my clinic in wheelchairs back in 2001 compared to today.  When I see patients today in wheelchairs, they typically are the same patients whose MS started before approved therapies were available.  To underscore my point, it is important to remember that we do not have reparative therapeutics at this point in time.  We only have therapies that modify the disease course moving forward.  Hopefully that will change in the near future as we are seeing early development of remyelinating agents (but it should be pointed out that remyelinating agents would not be expected to be helpful for patients who have lost brain or spinal cord tissue—i.e., the axon or wire which the myelin protects is gone).  I have come across a few patients who follow the literature and have decided to forgo treatment now and play the odds that a reparative strategy will be available to them soon.  While I hope for that for them, I cannot recommend such a course.  Treating early is best.

3.  What makes a neurologist not prescribe DMTs but suspect MS over several years?  Answer:  this is an area of debate among MS specialists.  We know that the natural history of MS tends to regress to the mean in respect to relapses and new lesions on MRI over time (i.e., the immune system and MS tends to weaken or burn itself out over time).  As I mentioned earlier, our DMTs are effective during the inflammatory stage of the disease.  So, when do we know that the inflammatory phase is done and we wouldn’t expect any meaningful benefit from the DMT?  The answer is, no one really knows.  Unfortunately, we can’t circle a date on the calendar as the day not to worry about another attack or more lesions on the MRI.  There have been investigations on taking DMTs off and see what happens.  One of my mentors, Dr. John Corboy at the University of Colorado, will be heading up a multi center study that would determine what patient characteristics would indicate that they can safely come off their DMTs.  In the past, I have used a very high bar to come to the conclusion that it would likely be safe to come off DMT:  1) no clinical disease activity (i.e. relapses) and 2) no new lesions on MRI scan over a 10 year interval.  The reason I use this is I find it highly unlikely that a patient can achieve that level of disease control over a decade and it be a result of the DMT they are on.  All current DMTs are partially effective.

Hope this helps.

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

Here is My Question:
Have any of the doctors read the FDA recent warning regarding fluoroquinolones? I was a healthy 54 year old prior to Cipro and now am totally disabled by tendon rupture, small fiber neuropathy, nerve damage from an anesthetic block given to repair the tendon and finally multiple sclerosis. Neurodegenerative diseases have been linked according to the FDA. When will the neurological community think outside the box?

Answer:
Excellent point. For those of you who have not heard about this warning it was released on May 12, 2016 by the FDA.

I’ve attached a link to this advisory for those of you more interested.  
http://www.fda.gov/Drugs/DrugSafety/ucm500143.htm


Common Flouroquinolones include

• ciprofloxacin (Cipro)
• levofloxacin (Levaquin/Quixin)
• gatifloxacin (Tequin)
• moxifloxacin (Avelox)
• ofloxacin (Ocuflox/Floxin/Floxacin)
• norfloxacin (Noroxin)

Generally, these antibiotics should only be used if there is no other choice. MS patients are often prescribed these medications for urinary tract infections. These antibiotics should only be prescribed for a UTI if they are the only antibiotic that the bacteria will respond to after culturing. 

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

Here is My Question:
Are IV steroids ever used to treat minor symptoms? I have numbness and some pain in my lower legs. I still walk fine but the sensations are very uncomfortable. Would IV steroids help with this?

Answer:
IV steroids are reserved primarily for clinically significant attacks that affect motor function (ie weakness, incoordination, and difficulty controlling bowel/bladder function).  Sensory attacks many times can be managed without steroids; however, there are exceptions. 

The sensory symptoms you are describing are less likely to reflect new inflammation (ie, a new attack of MS), but rather fluctuating symptoms as a result of older scarring to the nervous system.  An evaluation by a neurologist (or speaking with a neurologist who knows your disease is best). 

Symptomatic treatment is usually indicated (this is treatment other than steroids) for your current issues. You can read more at: 
​http://www.healthcarejourney.com/numbnesstinglingaltered-sensation.html

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

Here is My Question:
I am coming off of my MS meds. What should I expect?

Answer:
That is a great question. This depends on many things:

1. Where you are in the course of your disease? Specifically, your age and disease type and level of disability?

2. How active (relapse frequency and MRI activity) was your MS just prior to starting this therapy? How active has your MS been in the past year?

3. What disease modifying treatment you are taking, how long you’ve been on it, and how well have you’ve responded to it? Did you take this DMT as intended adhere poorly to the treatment schedule?

This provides some useful information to guide us in answering your question.

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

Here is My Question:
I am the 41 year old who asked about risk of PML with Tecfidera. Thank you for your extensive response. You were correct on most of the assumptions. I should have included that there was one enhancing lesion which was the one in the brain stem. Does knowing this now change anything in the response you provided? As an FYI I have increased my Vitamin D3 which went from 19 to 37.1 in two months. 

Answer:
Thank you for the added information.

The presence of an enhancing lesion, if all other lesions are consistent with MS and the brainstem lesion does reveal iron on gradient echo imaging (a capillary telangiectasia), is consistent with a diagnosis of MS. Based on your features, nothing else would change in my comments. If there were multiple enhancing lesion I would be inclined to start a DMT now. Without multiple enhancing lesions, you have the option of monitoring with frequent MRI. Some people do the repeat MRI imaging every 6 months for the monitoring. This is reasonable and cost effective. Afterall, disease modifying therapies cost up about  $60,000 per year.

The most important thing is to make sure the radiologist performed gradient echo imaging to exclude a capillary telangiectasia. Otherwise, these normal brainstem lesions (basically a birth mark in the brain) look just like an active MS lesion.

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

Here is My Question:
In November of last year my JV. Test was negative with a index value of 0.14. My most recent test came back abnormal/positive with a index value of 0.36. I'm currently on Gilenya after taking Avonex since my initial diagnosis on 2000. My neurologist suggested a oral medication due to depression and continuation of the flu-like symptoms after my shots. I'm worried if there are any other oral medications to help with my treatment. My current neurologist seems determined to put me back on a injectable although I have not had any new symptoms or relapse since 2008. I don't want to stop my treatments but I don't want to go thru the way I felt when I was getting weekly injections. Even the self inject pins resulted in me experiencing the flu like symptoms and no desire to do anything. 

Answer:
Your risk of PML is extremely low on Gilenya and there is no evidence that JCV virus index values modify this risk (i.e. makes the risk measurably higher or lower). Tysabri is the drug with the highest risk of PML by far,  and to my knowledge there has not been a case of PML yet in a patient with a JCV index level less than 0.4. So why would you worry about this index level on a patient not receiving Tysabri. 

I see no reason to stop your treatment with Gilenya based on the information provided. Bring this information to your neurologist and discuss with him or her again.

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

Here is My Question:
I am 41 years old and was recently diagnosed with RRMS. My symptoms were tingling in my hands and feet. My MRI showed three lesions (one on the brain stem). My neurologist wanted to give me Tysabri but I am JC + with a titer of 3.4. My doctor suggested Copaxone or Tecfidera. How worried should I be about PML on Tecfidera. My recent blood work shows lymphocytes at 1.1. Is Copaxone a better option.

Answer:
This is an excellent question; You seem to be a typical low risk early onset MS patient (you do not even satisfy current diagnostic criteria for definite MS if the information provided is correct). There are several, important missing pieces of information, so I will make several assumptions in my initial response. These assumptions are as follows:

1. There is no significant evidence of brain atrophy on your MRI scan
2. You only experienced sensory symptoms and have no limitations in function
3. There are no enhancing lesions on any MRI scans or new lesions on repeat MRI scans (these features would give you definite MS)
4. Your MRI findings are typical of MS. If not typical, sampling your spinal fluid would be the next step

If these assumptions are correct, you would be considered a low risk patient with many treatment options. I would list these options as follows

1. Start on High dose Vitamin D3 (5,000 to 10,000 IU a day depending on your 25 hydroxy vitamin D3 level) and repeat MR imaging 6, 12 and 18 months after the initial scan. If you should experience a relapse at any time or new MR activity on follow-up imaging, then initiate Disease modifying therapy. Rationale for this approach: In the CHAMPS and CHAMPIONS follow-up studies (these were part of a series of studies to determine if it is better to start treatment with an injectable at the onset of symptoms or after a person experiences recurrent disease activity), only 25 % of patients had less than 9 lesions on their initial MRI scan (you would fall into this group with 3 lesions). These patients did well over 10 years even if they received a  placebo until their disease flared up again or there was new activity on an MRI scan.  Many of these patients either never started a disease modifying therapy or stopped after several years of treatment and remained stable. It is reason to start high dose vitamin D3 therapy since it is safe in most people and there is mounting evidence it has some beneficial effect on disease activity. There is certainly no evidence of harm

2. Start on Tecfidera or Copaxone now: The downside of this approach is that you have no idea of your anticipated disease activity over the next few years in the absence of a disease modifying therapy. We do know that over the long term, starting treatment will reduce disease activity on a population basis but on an individual level only 20-25 % of patients with your characteristics will even experience a relapse in the first 2 to 3 years. Many people a concerned that without treatment their next relapse may be severe and they will not recover. In fact this is quite rare in people with your characteristics. This being said, many people with your characteristics are more comfortable with starting therapy now. This is certainly reasonable and the drugs are approved for this indication. So how do you decide? Primarily based on short term side effects, long term risks, convenience, tolerability and insurance restrictions. Assuming there are no insurance restrictions, options include the following in no particular order:

A. Copaxone: This is a partially effective drug with a long safety history that can be injected 3 days a week. The main side effects are injection site pain and lipoatrophy (loss of subcutaneous tissue at injection sites with divots developing in the skin)
There are no long term safety issues

B. Interferon: These are partially effective drugs with similar effectiveness to copaxone in patients like yourself. You would probably use a once a week (Avonex) or once every 2 week (Plegridy). Both are associated with flu like symptoms after injections that lessen with time and can be partially blocked by premedicating with tylenol or motrin. There are other minor risks but generally the interferons have an excellent long term safety profile. The advantage over copaxone would be fewer injections but only  if you are one of the individuals who does not experience significant side effects.

C. Tecfidera: This is a great drug with almost 200,000 people with MS taking it worldwide. There is evidence that it is more effective than Copaxone. This a twice a day oral medication. The main side effects are flushing and GI side effects (nausea, lack of appetite, upper abdominal discomfort, cramping or diarrhea); these side effects are generally manageable and lessen considerably within 8-12 weeks of starting treatment. The main long term risk is a lowering of absolute lymphocyte count. This may be associated with the development of rare infections like PML but the incidence is very low (so far about 2 per 100,000 patients treated).  JCV antibody index values have not been shown to be associated with risk of PML in patients on tecfidera. In your case, I might consider this drug second line along with Gilenya

D. Aubagio is an excellent choice as well: It is certainly as effective as any of the injectible treatments and all you take is a single pill very few side effects once a day. There are some concerns about using this in pregnancy but this is probably not an issue in your age group. The FDA recommends monitoring liver enzymes on this drug, but in my experience it is very rare to see significant liver enzyme elevations. Less than 10 % of patients experience some temporary hair thinning (usually not noticeable to others) on this drug, but this tends to reverse after 3-6 months of treatment. Generally, there have been very few short or long term risks with this drug, and I have not figured out why it is not used more often in early relapsing MS.

Tysabri is not a reasonable option; although a great treatment, your risk of PML after 2 years of treatment would be greater than 1 in 100

Hope this information helps.

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

​Here is My Question:
Can MS make your white blood cells to keep going down?

Answer:
Multiple Sclerosis has no effect on your white blood cell count; medications used to treat MS and other disease and other existing medical conditions can lower your white blood count

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

Here is My Question:
Any app for your cellphone to check your medicine to find out if it lowers white blood count cells?

Answer:​
I am not aware of any such web based app. Your prescribing doctor and your pharmacist are responsible for checking possible drug interactions that could synergistically lower a white blood count or create other problems. Many doctors use a very detailed web based app for this purpose but it is not free

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

Here is My Question:
How do I know if incontinence is related to MS? Under the assumption that an individual under 50 who has just been to the bathroom and who really needs to go after an hour while walking and empties bladder completely involuntarily, is not within the range of normal -even after a coffee- is that a correct assumption? - I need to know if this could be relevant to an MS workup before I report and get dismissed yet again with 'nothing to worry about.' Thank you : )

Answer:
Urinary frequency (the need to go in an hour) has many causes, mostly benign. Urinary incontinence unrelated to coughing, sneezing, straining or bending over (what is called stress incontinence) is definitely abnormal in someone under 50. There are many possible causes other than MS. A good urologist and neurologist working together should be able to figure out the cause of your  problem. Good luck.

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

Here is My Question:
Could neurotoxic drugs, i.e. quinolones cause white matter lesions that resemble MS? I have been diagnosed with small fiber neuropathy from possibly Cipro when a brain MRI showed white matter lesions consistent with MS? May I add that SFN and MS symptoms overlap? An MRI was ordered by my internist out of exasperation regarding my symptoms even though 3 neurologists looking at my neuropathy never ordered the MRI.

Answer:
Fluoroquinolones rarely cause neurotoxicity, usually in elderly with poorly functioning kidneys. The most common form of neurotoxicity is acute and consists of encephalopathy, seizures or abnormal movements. I did a Pub Med search for neuropathy, polyneuropathy or small fiber neuropathy associated with fluoroquinolone use and found no reports. There is certainly no documented association with cerebral white matter lesions. Many years ago there was some theoretical concern that the use of flouroquinolones to treat urinary tract infections in MS could be harmful, but this was never confirmed. This class of drugs is still used often in MS patients.
Hope this helps

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

Here is My Question:
Do you have any suggestions for those of us suffering from Lhermitte's sign?

Answer:
There is no specific treatment for lhermittes phenomena. I would recommend discussing options with your neurologist that are typically used to treat neuropathic pain, but this requires a lot trial and error to find something that works.

Benjamin M. Greenberg, MD, MHS
Vice Chair of Translational Research and Ambulatory Care
Department of Neurology and Neurotherapeutics
Director, Transverse Myelitis, Neuromyelitis Optica Programs
Co-Director, Pediatric CONQUER Program
UT Southwestern Medical Center
Childrens Health
Dallas, Texas

Here is My Question:
How often, if at all, should a follow up spinal MRI be performed if a spinal lesion has already been found? I've had no new visible brain lesions for a few years but don't know the status of my spine. 


Answer:
You will likely receive a different answer to your question depending on who you ask.  In my mind, the organizing principle behind when and what to image after the diagnosis has been made is to monitor the effectiveness of the therapeutic being used.

Approximately 90% of MS lesions on the brain scan are clinically silent with no perceived associated symptom which you'd be aware of.  Quite the opposite is true with the spinal cord.  When a new lesion established itself in the cord, symptoms invariable arise that you perceive and the neurologist can confirm on your exam.

If the purpose of cord imaging is to look for disease activity, I would rely on the symptoms and neurologic exam first before jumping in the loud clanking machine.

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

Question:
​What do you think about the Fasting Mimicking Diet?

Answer:
The fasting mimicking diet (FMD) is an interesting addition to the paradigm of the “anti-inflammatory diet”.  By using a low calorie and low protein diet for brief periods, researches hypothesize that this MAY help the MS disease process.   Earlier this month, Dr. Longo (from USC) published a paper on this topic where they first studied the effect of FMD on mice that have been given a condition called EAE (which is the closest disease state that appears like MS in mice).  They gave this diet to mice for 3 days every week and found that when compared to a control group of mice (i.e., a group that had a regular mouse diet), that the FMD mice had less disability and even 20% of the mice had complete reversal of symptoms.  They also found that the FMD mice had an increase of T-regulatory cells (which is a good thing), and a reduction of angry/inflammatory Th1 and Th17 cells (also a good thing).  Interestingly, they also found that the FMD mice appeared to have improved remyelination with a promotion of oligodendrocyte precursor cells (the cells that make myelin).

So, it appears that the FMD is helpful in mice that are given a disease that looks like MS, which is very interesting.  The next question is, will it help humans with ACTUAL MS?  The even more basic question is… is the FMD safe for humans to submit themselves to?

Dr. Longo’s recent paper reported a feasibility study where 60 patients with MS were randomized to a “control”, “Ketogenic”, or “FMD” diet.  The ketogenic diet is a high fat diet used to help treat children with difficult to control seizures, and served as a reasonable comparator arm in this feasibility study.  The patients were assigned these diets for 6 months and followed by the researchers.  What they found was the the diets appear safe; however, only 60% of the patients in the control diet group complied with the protocol whereas 100% did in the FMD group.  About 78% of the FMD group reported some adverse event (usually an airway infection, i.e., the cold) or a UTI.  The researchers also noted that the white blood cell count of patients being treated with FMD had a reduction of white blood cells by ~20% which then rebounded to normal after switching off the FMD diet.  Interestingly, they also saw a “mild reduction in” disability among patients using the FMD diet.

This is very interesting.  Dr. Longo and his colleagues have shown that mice with a disease like MS are benefitted by the FMD and that humans with MS appear to tolerate a FMD diet.  There is preliminary data suggesting the FMD may be beneficial in what matters for MS patients (namely stability/improvement of disability).  

So, what needs to happen now?

The short answer is:  1) this data needs to be replicated so we can have confidence that these preliminary findings are real, and 2) we need more data on the impact of FMD on actual patient with MS which would include not only neurologic exam findings, but blood monitoring (to determine what actually happens in the body when exposed to the FMD) and to assess FMD’s impact on inflammation in the brain and spinal cord in MS patients (i.e., through the use of MRI).

What is not clear based on the paper is the exact make-up of the diet used in the protocol.  Undoubtedly, the researchers are planning the next phase of testing.

For those interested in participating in research such as this, I would suggest you keep your eye on www.clinicaltrials.gov and search for ‘fast mimicking diet’.  At the time of this blog post, I do not see any actively recruiting trials, but I suspect that will change in the future.  On the .gov website you will find contact information for future studies as well as proposed locations for the research.  I would also suggest you discuss with your doctors about the safety of such a diet since everyone is different and other diagnoses for a given individual may make such a diet more risky.

Hope this helps,

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

Here is My Question:
I would like to know if there are no active lesions in the brain, how come my left leg is getting worse?

Answer:
Demyelinating events anywhere along the circuit between the cortex (surface of the brain) through the brainstem and in the spinal cord can lead to weakness in the leg.  A stable MRI of the brain doesn't really help answer the question you are asking.  Your neurologist should be able to help determine if a spinal cord event has occurred which can also cause weakness. 

Another possibility is that the MRI is not sensitive enough to see the demyelinating lesion to explain the problem.  As sensitive as the MRI is, it is not perfect.

Yet another possibility is no new lesion (or MS plaque), but degeneration of the circuit due to prior inflammation.  This can occur in what is known as secondary progressive (or progressive) MS. 

This answer is assuming that MS is to blame for the weakness.  You doctor can also evaluate for other potential causes (if appropriate) given your situation.

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

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