Here is My Question:
Hello, I am a 50-year old diabetic woman who began Tysabri treatment in 2010. For the past few years I've experienced frequent bouts of bacterial vaginosis. Metronidazole gel initially cured my symptoms but, is now ineffective. Do you have any advice or recommendations? My GYN and I would appreciate the insight. 

Answer:
Bacterial vaginosis is very common and both Natalizumab (Tysabri) and Diabetes increase your risk of this common infection.  You may or may not be able to prevent this problems from reoccurring but here are some suggestions:

You need to create an acidic environment in the vagina to nurture the growth of lactobacillus and other normal bacterial flora that suppresses the growth of yeast and harmful bacteria. You also need to decrease the amount of glucose in your urine; this glucose in the urine feeds the harmful bacteria and yeast in the vagina that upsets the normal balance of bacteria flora. Lastly, you need to keep the area dry, if possible; any problems with urinary accidents, even small amounts, will further increase the risk of infection. 

How do you do all of this? 

1. Take Probiotics with Lactobacillus and/or eat Yogurt with live cultures and other fermented food
   
2. Drink some vinegar daily to acidify the urine. Ask your Doctor about intravaginal boric acid 
   
3. No Douche washing. This actually makes the situation worse
   
4. Better control of blood sugars; specifically, use a urine dipstick to make sure you aren’t spilling glucose in the urine

It is not at all clear why Natalizumab (Tysabri) is associated with an increased risk of vaginosis but this seems to be a reproducible finding. If your MS is well controlled on Natalizumab (Tysabri), you may consider extending the interval between infusions to every 8 weeks.  This may allow for more recovery time. Many individuals who are JC virus antibody positive increase the interval between infusions, because this change  in the dosing interval has been shown to dramatically lower the risk of PML. Most MS specialists have not noticed a significant decrease in the efficacy of Natalizumab (Tysabri), when you increase the dosing interval. In fact a clinical trial is planned to prove that increased dose intervals do not alter the effectiveness of Tysabri

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:
Differential Diagnosis of MS - How Likely is Microvascular Ischemic Disease for A 35 Year Old?

My latest MRI report stated: 11 foci of hypertensity (FLAIR) predominately in the subcortical white matter of the cerebrum bilaterally. Of course it goes on to state that nothing abnormal was found on other sequences...

The list of differential diagnosis included migraines, demyelinating disease, vasculitis and microvascular ischemic disease. 

I’ve never had a migraine (ruled out by neuro) and don’t have primary or secondary vasculitis (ruled out by rheumatology twice). My MS Specialist felt my symptoms suggested Multiple Sclerosis. 

My question is: How likely is microvascular ischemic disease in a patient who is 35 and has no risk factors? No family history of strokes, no personal history of diabetes, normal (to low) blood pressure, normal lab work (for almost anything you can imagine to rule out MS), low stress lifestyle, etc. 

​The MRI report also mentioned that this amount of hyperintensities is not atypical of a patient of my age. I was under the impression that 1 lesion per decade was at the upper limit of normal until the 60’s, then these changes begin to become apparent. 

Answer:
In general, microvascular changes in 35 year olds with no risk factors are rare, but can happen. Sometimes family history contributes, sometimes the changes are not microvascular changes but enlarged perivascular spaces. The key is the interpretation and getting another neurologist or neuroradiologist to review controversial MRIs (ie second opinions) is often a good idea.
 
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:
In 2012 I had an episode of severe vertigo and my eyesight even changed overnight. Then over the years I had weeks here and there when my face would go numb or I had pins and needles here and there.

I'm also having short term memory issues. An MRI in 2014 of my brain and neck on a 1.5 T only came back with nonspecific white matter.... then in January of this year my body started going haywire with numb legs, spasms, speech slurring when hot, forgetting what I was doing right in the middle of something, tongue tremors, facial numbness again, zaps along face, zaps around ear, and now burning sensations in legs constantly, leg and arm weakness, internal vibration feelings, twitches etc.

I had a spinal tap done and there was no bands but the CSF index was flagged high but just at the mark where it would be flagged. The notes on the CSF panel state that there are reactive lymphocytes and plasma cells present.

I am in limbo and need this to stop. My doctor is saying small fiber sensory neuropathy. I just don’t see how! The portion of the CSF index states this provides support for the diagnosis of MS. I did have MRIs this year and there were two active high intensity spots and a few non active spots. Should I seek further diagnosis? The medicine she prescribed Gabapentin or something like that even made my burning sensations worse... 

Answer:
You are certainly experiencing a wide variety of unpleasant symptoms but I could not diagnose either MS or a small fiber neuropathy based on your description.

Remember, MRI findings and CSF findings must be interpreted in the context of your age, other medical conditions, symptom history and findings on examination. It takes a good doctor to piece this all together. If CSF findings or MRIs were diagnostic of anything, you really wouldn’t need a neurologist. Perhaps all you need is a second opinion. Why not ask this doctor to send you for a second opinion?

Good luck

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:
Are there any contraindications for receiving Tysabri, Taxol and Herceptin infusions on the same day? It would make it easier on me not to have to travel 45 miles twice in a week.

Answer:
The answer to this question depends on many different factors. It is probably not a good idea to combine these treatments in general.

Infusion reactions can occur with all three medications and it would be difficult to know which drug was causing the reaction.

Using taxol and Tysabri together could also increase the risk of serious infections.

This is a conversation your neurologist and oncologist need to have with each other. They are the only ones who know your clinical history in enough detail to answer this question thoughtfully

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'm going to be starting Rituximab Infusion soon. I have Relapsing MS. Can you explain how this infusion works? 

Answer:
Rituximab is a chimeric monoclonal antibody engineered to bind to and kill any cell in your circulation that has a protein on it’s surface called CD20. CD20 is primarily expressed on the surface of B cells, a subtype of lymphocyte, making this a very selective therapy that leaves the rest of your immune system unaffected.

The B cells destroyed by rituximab are thought to be heavily involved in both the development and persistence of the inflammation associated with Multiple Sclerosis. This is the likely reason that Rituximab is so effective in relapsing forms of MS, a stage of the disease where injury to the nervous system is primarily caused by new and persistent inflammation.

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

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Question:
Can MS cause bone pain that lasts for months?

Answer:
MS doesn’t directly cause bone disease.  Bone thinning can be seen as a result of chronic medication use associated with bone loss in addition to immobility and reduction in weight bearing activity.  True bone pain should be evaluated through a primary care physician first as MS is not a direct cause for this symptom.

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

Here is My Question:
I am 48 years old, and been diagnosed with MS officially for 17 years. I have had no relapses since 2005 when my last child was born. I have been on Copaxone since then as well. It is being recommended due to heavy bleeding that I get a Mirena IUD implant. I have fear about it causing a relapse. The information provided In the literature I can find is insufficient. Can it cause a relapse?

Answer:
I wouldn’t worry about this IUD causing a relapse.  Hormone manipulation used for infertility protocols can precipitate a relapse but that is not related to IUD material/medication.

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

Here is My Question:
I'm a working female in my late 30s with RRMS. I am doing ok with it, but it is the secondary stuff I am trying to learn to live with.

What is the priority to handle: sleep cycle disturbance or daytime fatigue? They're both negatively affecting one another.

I'm dragging myself to bed between 10 and 11pm nightly (can't go any earlier). I am up between 3:30 and 4am for a variety of reasons (not often MS symptom related...I'm a light sleeper), and I can't go back to sleep. Once I'm up, that's it! By mid-day, I'm a walking zombie. I can't function without caffeine around 2 or 3pm. Wash. Rinse. Repeat. 

I am already on 100mg Amantadine in the morning and 50mg before 1pm, but it hasn't really done much. Sleeping pills make daytime drowsiness so horrible.

How can I get more sleep and more energy? Help!

Answer:
Managing daytime fatigue and sleepiness  must begin with a thorough evaluation of altered or disrupted sleep. You can only beat the proverbial, “dead horse” so much with caffeine and stimulants . It sounds like you have longstanding problems as a light sleeper but were able to compensate in the past. Common problems to address include the following:

1. Altered sleep cycles: Doesn’t seem to be an issue with you
   
2. Poor sleep hygiene: This includes no caffeine or stimulants past afternoon, no alcohol, taking time to meditate or practice mindfulness before bed; sleeping in a dark quiet room (no TV) and getting out of the bed (and room) if not asleep in a reasonable amount of time
   
3. Frequent awakenings: These have many causes including anxiety with rumination, depression, urination frequency, discomfort or spasms, noisy sleeping partner, problems with your sleep environment or sleep disorders (sleep apnea for instance). Your doctor should be able to help with this assessment or you may need an evaluation in a sleep clinic

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

Question:
I have had MS since 1999. My original MRI showed cspine and periventricular lesions. I now have confluent cspine lesions and a small lesion in medulla, scattered brain, small. I've had no cognitive lesions and have had 10 years of neuropathic pain. Now it is very severe and chronic. When feet are dependent, see sun, or minimal, heat...they get red hot and swollen. Occasionally they will look blue and mottled. My pain is chronic despite all medications. I've never used opioids. My last resort was IV lidocaine every 2 weeks. Is there any hope of relief? My walking is deteriorating, and my muscle mass is deteriorating because of my lack of exercise. Please advise. Thank you.

Answer:
Red, painful, hot to the touch, swollen feet that begins intermittently on exposure to heat or exercise and becomes chronic over time may be caused by a rare condition called erythromelagia. The key to the diagnosis is the following:

1. The feet not only feel hot to you but feel hot to anyone touching them
2. There is no evidence of infection
3. The pain is improved by soaking the feet in cold water

You may want to be referred to a neuropathic pain specialist if there is one in your region.

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

Question:
Is there any correlation between MS treatment and development of cancer?

Answer:
That really depends on the treatment. There is real or potential increased risk of cancer with many MS treatments but the risks are usually quite small.

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

Question:
My OB GYN has recommended surgery to remove a uterine polyp. Currently I am being treated with Ocrevus. Second half dose was 7/3/18. She has concerns with anesthesia and risk of infection. My current neurologist doesn’t have a lot of feedback. He simply states - you aren’t really as immunocompromised as a chemo patient. My first full dose is scheduled for 1/4/19. Do you have any feedback on the best course of action?

Answer:
There should not be a significant increase in the risk of post operative infection shortly after starting Ocrevus. It should also not interfere with normal healing. 

The most common infections in people on Ocrevus are upper respiratory tract infections and these are more common after long term treatment. 

I am not what concerns he or she has with anesthesia or the type of procedure anticipated.
 
Revere (Rip) Kinkel MD
Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Question:
I'm going to start Tecfidera next week as I was on AVONEX for 9 years. Do I have to keep the same time to take it and the week after because of twice daily dosing? How much time should I leave between them? Thanks

Answer:
There is no particular reason to delay starting Tecfidera after treatment with Avonex, as long as your baseline blood work is normal. Tecfidera is taken twice every day. We usually advise people to take it with breakfast and dinner so they remember to take it with food.

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

Question:
​The neuropathy in my feet seems to be getting worse, even though I'm taking more gabapentin. What does this mean?

Answer:
The answer to your question depends on the cause of your neuropathy. Strictly speaking, MS does NOT cause a neuropathy although MS patients do experience a form of neuropathic pain related to demyelination in the spinal cord. This is a common source of confusion in MS patients.  The term neuropathy refers to diseases of peripheral nerves such as diabetes. As most of you know, MS only affects the central nervous system and the root outlet zone of various nerves. 
Neuropathic pain, regardless of the cause, can fluctuate significantly from day to day based on a number of factors including temperature, degree of immune activation, electrolyte balance, or alterations in medications. These fluctuations do not necessarily mean that there is increased damage occurring in the affected tissues.

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

Question:
Should I take Duloextine and Pregablin together, both at high dosages?

Answer:
Duloxetine (cymbalta) and Pregabalin (Lyrica) are excellent combination therapies for chronic neuropathic pain. The advantage of combination therapy is the ability to use lower doses of each individual drug to achieve your outcome with few side effects than pushing the dose of an individual drug. We usually use combination doses of 60 mg/day of Duloxetine and 300 mg/day of Pregabalin. Of course, if these doses are not effective in combination the individual doses can be increased one at a time depending on tolerability.

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

PLEASE NOTE:  The information/opinions on this site should be used as an information resource only.  This information does not create any patient-HCP 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.

Question:
I have been on Aubagio for two years. My WBC's have been slowly declining, and now are low (3.7, NL 3.8) with abs. neutrophils 1828 (NL 1500). Gammaglobulins are 0.5 (NL 0.8), Kappa 129, Lambda 62, KAPPA/LAMBDA ratio 2.08. RBC's showed mild anisocytosis and poikilocytosis. Band and activated lymphocytes present. Are any of these abnormalities related to the Aubagio (besides the WBC's)? Thanks.

Answer:
A low White Blood Count (WBC) on Aubagio is relatively common with long term treatment (15-20 % on the 14 mg dose). Most of the time this is mild, as in your case, and does not require an adjustment in treatment. The most important thing is to make sure your absolute lymphocyte count stays above 500 and absolute neutrophil count stays above 1000 (yours is 1828). 
​
The mild anisocytosis and poikilocytosis refers to abnormal size and shape of red blood cells. This can occur with stressed bone marrow, anemia, liver disease and kidney disease among many possible causes. This is usually of no significance but your doctor can let you know if it is significant in your case.

You should definitely have your blood counts monitored more closely than usual and ask your MS specialist if he or she thinks these findings are significant in your case.

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 has a previous lesion from a year ago grown from 0.5 cm to 1.9 cm? I have no symptoms, and am not on a DMD.

Answer:

Lesions can appear larger on repeat MR imaging for several reasons:

1. Technical reasons: for instance, a higher resolution scan (3 tesla instead of 1.5 tesla) can identify a greater extent of a lesion and make it appear larger on repeat imaging. Usually the changes in lesion size in this situation are less than 25 %. Your lesion is 280 % larger, so this seems like an unlikely explanation unless different parts of the lesion were measured at each time point. Essentially this would mean they were comparing apples to oranges. Remember MS lesions tend to have odd shapes with varying diameters in different directions of measurement.
2. Greater edema surrounding an acutely enlarged lesion. These enlarged lesions usually shrink with resolution of the edema (basically excess water in the tissue) but may always remain larger than the initial lesion.
   
3. The MS lesion can enlarge along its leading edge because of continued progression. These enlarged lesions are less likely to shrink unless also associated with edema
   
4. Another process is taking place: for instance, what was thought to be an MS lesion was really another chronic condition. This is more likely if the enlarging lesion is the only lesion in the brain or if it has atypical features or if the individual is at risk for other conditions like PML.

Hope this helps answer your question.

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:
Is there a protocol for discontinuing Avonex other than cold turkey?

I have been taking Avonex since May, 1997, and missed one injection. My MRI's and I have been stable for over 10 years. My neurologist and I discussed this recently since the powder form will not be available soon. The pen is another consideration as long as my side effects don't worsen. What are your thoughts?

Answer:
It is not possible for me to determine, based on the information provided, whether you should consider stopping Avonex. There is no protocol for stopping this medication and no evidence of rebound or immediate worsening after stopping Avonex.

Please discuss the reasons for stopping Avonex further with your MS specialist before making a final decision

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