Mindfulness Meet Up: Today at 4PM

You are invited to a Zoom meeting.
When: Mar 27, 2020 04:00 PM Pacific Time (US and Canada)

Register in advance for this meeting:
https://zoom.us/meeting/register/uJEocO2hrTouyTz_g0Q6pyQrwRjTFi2YDQ

Also, check out all the events for Adapt Movement here:

https://adaptmovement.org/event/friday-mindfulness-meetup/ 

Adapt Movement and HealthCare Journey

Part II: What we think we know
 
As is often the case, what we think we know in medicine exceeds our grasp of the actual facts. This does not mean we cannot make logical assumptions, better known as educated guesses, based on our prior medical experience with other viral infections. These experiences must guide our advice and recommendations to patients and families until we have a better understanding of COVID-19.
 
First, we do not know how people with multiple sclerosis respond to a COVID-19 infection. When I talk to colleagues in Italy, which is slightly ahead of us in terms of the pandemic, they know their MS patients are getting sick, but they’ve had no time to determine if certain MS patients are more or less susceptible to severe disease. Even my colleagues in the USA are starting to tweet about their anecdotal experience with COVID-19 infections in isolated MS patients. 

These anecdotes are reassuring, but not terribly informative. Since 80-90 % of people with a COVID-19 infection experience relatively mild disease, it is not surprising to hear that individual MS patients on various disease modifying therapies (DMTs) recover well from their COVID-19 infection.

​For the time being we need to pay attention to what we know for sure and not jump to unnecessary conclusions. Here is what we think we know.
 
As pointed out by recent publications from China and in my last blog, there are several risk factors for COVID-19 related pneumonia (severe disease) that apply to everyone, including MS patients.  These known risks include age over 50 (particularly age over 65), male sex, hypertension (treated or untreated), diabetes and cardiovascular disease.  What seems to be unique about COVID-19 infection is the unusual link between the severity of infection (pneumonia) and high blood pressure.

We do not usually see a link between infectious diseases and high blood pressure. Experts on corona viruses tell us that COVID-19 uses a receptor on the surface of cells that line the respiratory system to infect your upper and lower respiratory tract. This receptor, called the angiotensin II receptor, is more numerous (up-regulated in scientific jargon) in people with high blood pressure, apparently making those individuals with high blood pressure wonderful targets for this virus. 

You can think of the angiotensin II receptor as a lock and the COVID-19 virus happens to possess a very good key to that lock, opening the door into your respiratory system.  This seems to be the way that the COVID-19 virus infects all people, not just people with high blood pressure, since we all express the angiotensin II receptor in our respiratory system. However, other factors must be responsible for the increased risk of more severe infections with COVID-19 in people with high blood pressure. 

One possibility is that certain medications taken by people with high blood pressure increase the risk of severe COVID-19 infections by further increasing the number of angiotensin II receptors in the lung or changing other characteristics of the angiotensin II receptor. Stay tuned for more information on this topic that may even be relevant to prevention or treatment. Suffice it to say that most people with high blood pressure with or without treatment will experience mild disease.
 
 
We also know from years of experience and research studies in people with MS and other neurological diseases that there are other factors known to increase the risk of severe respiratory tract infections. These risks include physical disability in any age group defined as anyone spending time in a wheelchair, a prior history of frequent upper respiratory tract infections, pulmonary disease (e.g. asthma, COPD), smoking and immunosuppression. There is no reason to believe that these same characteristics would not also increase the risk of severe COVID-19 infection.  
 
So how do we put all this information together to provide advice to our patients with MS based on, what we think we now?
 

1. Follow the advice of the CDC and your state health officials. We cannot emphasize enough the importance of social distancing, washing and sheltering at home as much as possible.
   
2. We have no reason to believe that relapsing remitting MS patients without physical disability are at any greater risk of severe COVID-19 infections than their healthy peers as long as they do not have any of the risk factors discussed previously (i.e. age > 50, male sex, high blood pressure, diabetes or cardiovascular disease, pulmonary disease, smoking, frequent respiratory infections or immunosuppression)
   
3. It is prudent to avoid or postpone immunosuppression with lymphocyte depleting agents, particularly if you are over age 50, a male or have a diagnosis past or present of hypertension, diabetes or heart disease.  Lymphocyte depleting agents include rituximab, ocrelizumab (Ocrevus), Mavenclad (Cladribine), lemtrada (Alemtuzumab) and chemotherapies used to treat MS (cyclophosphamide is an example). There will definitely be some people with MS, whose disease is so active that it is too risky to postpone treatment, but most people will be able to delay treatment with lymphocyte depleting agents until the risk of COVID 19 infections pass.
   
4. We do not know if Natalizumab (Tysabri) will increase the frequency or severity of COVID-19 infections. Some studies, notably studies of Tysabri in Crohn’s disease, reported a slightly increased risk of respiratory tract infections, but this risk was not the observed in the MS studies. Tysabri alters normal immune cell trafficking and interactions with the extracellular matrix, particularly in the central nervous system and GI tract, but this does not suppress immune cell function, notably. Some MS specialists may increase the interval between infusions to every 6 to 8 weeks during the pandemic to allay this potential concern. It is important not to stop Tysabri altogether, because of the risk of a rebound relapse.
   
5. We have no reason to believe that Beta Interferon treatments (i.e. avonex, betaseron, rebif, extavia and plegridy) will increase the risk or severity of COVID-19 infections. In fact, interferons are being studied as a potential anti-viral treatment for COVID-19 infection.
   
6. We have no reason to believe that Copaxone and glatiramer acetate will increase the risk or severity of COVID-19 infection
   
7. We do not know if Aubagio, tecfidera, gilenya or mayzent will increase the risk or severity of COVID-19 infections. It is possible that people with MS who experience a significant lowering of their lymphocyte counts on any of these DMTs could experience an increased risk of severe COVID-19 infections. Some MS specialists may alter the dose or dose frequency of these medications, if you are considered at increased risk for severe COVID-19 infection. Talk to your MS specialist to see if you fall into this category of people with MS. But remember that people on Gilenya and Mayzent may also experience a rebound relapse if they suddenly stop treatment.

 
What will happen if you do experience a COVID-19 infection?

Perhaps nothing. Some people just experience mild cold symptoms and some experienced only an alteration of taste and/or smell. Most people feel like they have the flu with fever, body aches, fatigue, congestion and cough. People with MS can expect their MS symptoms to worsen with a COVID-19 infection because of fever and/or a general activation of your immune system. If you do get ill, make sure you stay well hydrated and keep your temperature down with Tylenol (acetaminophen). If your MS worsens significantly your MS specialist may even consider treating you with steroids depending on the severity of the COVID-19 infection. But the best thing to do is not to get infected at all
 
Good luck and stay well

Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

During the past 2 weeks we have witnessed a transformation of society and our health care system unlike anything observed for almost 75 years, since the upheaval of WWII. The stress created by our response to all the uncertainties surrounding current events can have a negative impact on our relationships and our health, if we let it. So how do we minimize this stress? In many ways this is an existential question. None of us have as much control over our lives as we imagine. Any day something bad could happen to a friend or a love one and we never know when our own time will be up. You may be thinking, Wow, that’s a downer thought. Instead, it is meant to be liberating. If you consider and embrace this idea, you will live each day more fully and learn to appreciate and interact with those around you in a more positive light.

If you can do this--and for many I’m sure your faith or religion helps-- then you can turn your mind away from uncertainty, fear, blame and other negative thoughts and focus on events you can control. If you do this, you will also realize there are many people out their, even in your own community, who may need your help; help with supplies and food delivery or simply a friendly and kind voice to call and check on them. It is with these thoughts in mind that I offer you a three-part blog on what you, as people with MS, need to know about COVID 19 with an emphasis on those things you can control. The advice in part I apply to almost anyone with chronic health conditions, but part II and III will focus more specifically on MS.
 
The best strategy for dealing with a pandemic of a highly contagious, incurable infectious disorder is to close down all activity, isolate us from human contact to prevent the rapid spread of the illness and thus avoid overwhelming the health care system. You’ve all heard the term repeated on the news: “flatten the curve” or slow the rate of infection so there are enough hospital beds at any point in time to care for those with severe illness. For those with chronic medical conditions there is a unique concern; namely, will the health system be available to help you with your condition if overwhelmed with the care of COVID 19 infected individuals. The answer is yes but you must get used to doing things differently and adjust expectations for the time being.
 
Part I: What we know (for sure):
1. We must slow the spread of infection to save lives, including the lives of people with MS, by switching to Video Visits or Telephone Visits instead of in person visits: case fatality rates (deaths) are 5 % or greater when the health system is overloaded and about 1 % when the system can handle the volume of infected patients; For those with or without MS or other chronic diseases, this means avoiding contact with individuals potentially exposed to COVID19, paying attention to social distancing, frequent hand washing and cleaning of any surface potentially contaminated. One of highest rates of infection is currently among health workers and one of the best places to get infected is in a hospital, emergency room, urgent care center or doctor’s office. THEREFORE, YOU MUST PHYSICALLY STAY AWAY FROM THE HEALTH SYSTEM AS MUCH AS POSSIBLE DURING THE PANDEMIC. This is only difficult if no one knows what is causing your medical problem. For those with a known or suspected diagnosis of MS it is now essential to use video and telephone visits to keep social distance from the health system. There are few reasons for anyone with MS to see a doctor in person until they’ve had a video or telephone visit. Even if you think you’ve been infected with COVID19 or are displaying COVID-like symptoms (fever, dry cough, headache, runny nose, sore throat, fatigue, and muscle aches) you do not need to see a health care worker in person unless you are experiencing difficulty with shortness of breath, difficulty keeping down food or fluids or experience significant worsening of your MS that does not respond to lowering your temperature with Tylenol (Acetaminophen). Find out how to do video visits with your doctor and insist on this type of interaction unless a visit is necessary or the pandemic is over.
 
2. The experience in China tells us that the people at highest risk of complications from COVID 19 are those greater than 50 years old, men and people with hypertension, diabetes and heart disease. There is no reason to believe this is different in MS patients. People with any of these risk factors should be particularly cautious; but remember, the vast majority of people with these risk factors, even if you have all three risk factors, WILL NOT experience severe disease. Furthermore, the disease can be severe even if you do not have these risk factors. As an example, 40 % of current COVID 19 admissions to US hospitals involve people under the age of 40. Make sure your family members or contacts are aware of this information. This information should not be used to create either fear or complacency. Use this information instead when deciding whether you plan to relax any of the current restrictions associated with the pandemic. As the number of cases begins to fall and life starts to normalize, it may be prudent for those with greater risk factors for serious illness from COVID 19 to maintain their vigilance and restrictions a little longer than the rest of the population.
 
So that is what we know so far. It is not a lot but it is very helpful information. In part II of this series, I will address what we think we know about the effects of COVID 19 in different MS patient scenarios. This is also important information but it is not written in stone and could change as we learn more. Stay tuned.

​Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Join us for a virtual exercise class!!

​Check it out at the link below:
https://linktr.ee/adaptmovement

If you have any questions or issues connecting, please contact Adapt Functional Movement Center at (760) 688-7323

Well, St Patrick's day has come and gone without any drunken fanfare this year, at least in public. If the run on alcohol at Costco and Target is any indication there were a lot of people getting drunk in their quarantined homes.

UCSD had 12 cases with COVID-19 hospitalized as of this morning. We seem to be doing better than northern California, at least at present, but time will tell. We have converted most in person visits to the MS Center to MyChart Video visit. If you are one of our patients and would like to consider Video visits during the Pandemic, please send us a MyChart message. It is more than likely that we will contact you first.

For those living in San Diego County, we now have drive up testing for COVID-19 for those people with suggestive symptoms. This testing is free. You can call the UCSD nurse triage line at 800-926-8273 if you have suggestive symptoms (fever, sore itchy throat, cough or shortness of breath) and want to know if you qualify for tested. The send out lab is now guaranteeing more rapid results on testing, even within 24 hours.

If anyone is interested in a video demonstration of how this virus spreads so fast and why isolation and social distancing is so important please see this posting from the Washington post:
https://www.washingtonpost.com/graphics/2020/world/corona-simulator/

For up to date information on COVID 19 I would recommend the following sites;
CDC coronavirus webpage
California Department of Public health webpage
Massachusetts Department of Public health webpage

It is extremely important that all people with neurological disability (impaired mobility requiring assistance to walk), especially those over 55, those with other medical problems (Diabetes, cardiac or pulmonary disease) and those who have received immunosuppression in the past 18 months (this includes rituximab, Ocrevus, Mavenclad (cladribine), Lemtrada and any chemotherapy) remain at home and avoid contact with individuals who may have been exposed to COVID-19.

To help with this drastic quarantine initiative, the Adapt Functional Movement Center in Carlsbad California is mobilizing to provide assistance to those members of our community stuck at home and unable to get necessary supplies

Please read the post from John Monteith, the director of the center. If you need assistance, please follow the link in his message to provide your information (click here)

If you are NOT in North County San Diego please go to your local neurologist for any medical emergencies or contact the MS Navigator with the National MS Society at 18003444867

Keep Well
Dr Kinkel

Here is My Question:
I want to get a tongue piercing but I don’t know if it’s safe since I just recently got diagnosed with MS and I’m not sure if it will effect my health.

Answer:
​Definitely avoid any tongue piercing until the COVID 19 pandemic passes. After the pandemic you will only have to worry about what your mother will say about the piercing.

Stay healthy

Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

How to Arrange Telemedicine Visits with your MS Specialist

Due to the COVID 19 (Corona Virus) Pandemic many health care facilities are converting in person clinic visits to telemedicine video visits. This will diminish your exposure to the virus and allow the health systems to divert needed medical personnel to care for those already infected by the virus.

If you are a patient at UCSD (University of California San Diego), please follow the instructions posted below to set up a Video Visit capability with your MS specialist, regardless of whether you are currently scheduled for a visit. You must be in California at the time of your video visit to use this system.

If you are not a patient at UCSD, please contact your local MS specialist and see if they have the capability of performing video visits. This capability is built into the EPIC electronic medical records system used by many health systems in the united states including all University of California health systems. If your MS specialist is at a facility that does not use EPIC, it is likely they have a different system available for video visits.

Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Because of coronavirus concerns, the MS Expo will be postponed until June 6th. Please share this information with others.

HealthCare Journey

When Biogen did clinical trials on Tecfidera did they test the efficacy of the drug at half dose?
Thank you.

Answer:
Yes they did; Half dose Tecfidera (240 mg total dose per day) is not effective in treating MS.

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 recently asked the question about whether or not to delay my Ocrevus due to the coronavirus. I am in Louisiana and there is currently a case here now. I was considering getting an MRI to make sure I don’t have new or active lesions and possibly checking my B cell count. My questions are:

1. If my B cell count is around zero, how long would I expect it to take for them to be high enough to make me no longer immunocompromised?

2. If it will be low for a long time, would it even matter if i had the infusion now?

3. Is it worth checking the B cell count or do you feel that it is not useful and that we should just assume we are immunocompromised on Ocrevus regardless of the number?

4. At this point with the COVID19 spread, if I and MRI showed new or active lesions, would it still be more of a risk to get the infusion versus waiting a few months?

Thank you for your help. I have a terribly hard time getting through to my MS specialist and her office is not responsive to my questions.

Answer:
B cell Depleting therapies and the COVID 19 Pandemic

These are really good questions. All of them have been asked in one form or another lately by our MS patients receiving treatment with monoclonal antibodies that deplete CD20 expressing lymphocytes (predominantly B cells).  Let's begin with what we currently know about these therapies;

1. Anti-CD20 monoclonal antibodies (rituximab and Ocrevus) are very effective for relapsing forms of MS and mildly  effective for primary progressive MS patients under the age of 55. We do not know the effectiveness of this therapy in older patients (those over 55); This is important information when considering the potential upside of treatment in your situation
2. Treatment with anti-CD20 monoclonal antibodies, particularly repeated treatments every 6 months, increases your risk of upper respiratory tract infections and pneumonia. This risk is highest in older patients (over 55) and those with significant disability (requiring assistance to walk or Wheelchair bound). It is also higher in those with other medical conditions like diabetes, pulmonary disease or vascular disease and in smokers. The risk of respiratory infections is also higher if your IgG or IgM total antibody levels fall below the lower limit of normal. This is a common blood test your doctor can order. This is information to consider when determining the potential downside of treatment in your situation.

For those on treatment with anti-CD20 monoclonal antibodies already:

1. The benefits from a single infusion can last from 6 months to several years. There is no definite biological marker that tells us when the effects of a single infusion wears off, but a return of disease activity is more likely once central memory B cells return. These cells have certain markers on the cell surface (CD19+CD27+) and can be easily measure with a blood test. The duration of benefit may increase after many cycles of treatment. This means that a person who has already received greater than 2 cycles of treatment may be able go longer before needing another infusion compared to a patient who has received only 1 cycle of treatment. However, the risk of infections goes up with repeated cycles of treatment every 6 months.
2. The risk of complications from COVID 19 (corona virus) are expected to increase in those on regular infusions of anti-CD20 therapy. This is particularly true in those who are older, more disabled, have immunoglobulin deficiency or  have other disease mentioned previously. Again, this risk is further increased in smokers. This information can be used to decide if your definitely delay further cycles of treatment.

In general we are delaying anti CD20 treatments during the COVID 19 outbreak until there is a return of central memory B cells or even longer if other risk factors are present or the patient has been stable by MRI and clinical examination for over a year. Following this protocol many of our patients are going over 1 year without repeat treatment and sometime much longer.

​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:
Do swollen lymph nodes go down if I stop taking Copaxone?

Answer:
Swollen lymph nodes from Copaxone (Glatiramer acetate or Glatopa) injections, whether painful or not, should decrease in size over several weeks, if the Copaxone is stopped. If they persist or enlarge further, your doctor may consider a lymph node biopsy to make sure the swelling is not due to another cause.

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 you aware of any studies relating to Tecfidera where the efficacy of the drug was tested at half its potency? I understand from my own searches that Biogen conducted trials at double the current recommended strength but not at half the recommended strength. Do you have any understanding about why companies conduct their trials in this way?

Answer:
The common paradigm for drug testing after preclinical evaluation (ie, animal testing) is to complete Phase 1 that looks at how the body handles the investigative therapeutic (ie, the pharmacokinetics and pharmacodynamics) which helps inform potential dosing for larger trials. Phase 2 may involve dose ranging studies based on Phase 1 and the goal is to get an idea if the medication will work for the disease being studied. Phase 3 testing confirms that the medication works but also gets a better sense of safety. The first 3 phases are required for consideration of approval by the FDA. Phase 4 is post-marketing safety evaluation (longer term safety). It is not surprising that pharmaceutical companies in general will seek to test the maximally tolerated dose because the thought is "more is better". If you give too little medication and it doesn't show benefit, that means they've lost a lot of money doing the experiment with no return on their investment (ie, greater chance they couldn't get it approved by the FDA). What you are getting at is doing experiments for the "lowest effective dose". I wish that would be part of the approval process (ie, mandatory dose ranging studies), but sadly, it is not.

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

Here is My Question:
According to the research I read just today, 3/2/20, high doses of Vitamin D could have negative effects for those with MS. I take 10,000 IU daily. Should I stop? I have PPMS.

Answer:
We have always known that high levels of Vitamin D from excessive supplementation can cause hypercalcemia from Vitamin D toxicity.  Studies in humans suggest that Vitamin D doses at or under 10,000 IU daily are safe and tend to raise Vitamin D levels no higher than the upper limits of normal, as long as the person does not have other health concerns that could affect vitamin D levels. Doses of vitamin D supplementation above 10,000 IU daily, usually much higher doses, can raise Vitamin D levels too much and cause hypercalcemia (high calcium levels)

The "research" you refer to in your message was recently reported at the ACTRIMs meeting. The investigators did not study people with MS; Instead, they studied different doses of Vitamin D supplementation in a mouse model of brain inflammation, called EAE. Somewhat expectedly, modest elevations of Vitamin D levels to the upper limit of normal prevented the mice from experiencing severe disease, whereas super high doses (75,000 IU daily) worsened the disease. They attributed the disease worsening not to the high vitamin D levels but to the effects of high calcium levels on the activation of inflammatory T cells, a type of lymphocyte.

It is very easy for your doctor to determine if you are taking too much vitamin D. This can be done by checking vitamin D levels, PTH levels and calcium levels

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 am being switched from Rituximab to Truxima for my next (3rd) infusion. I am worried about a change and if Truxima has been tested at all on MS?

Answer:
Truxima is a biosimilar rituximab that was reviewed by the FDA.  It's labeling is Truxima (rituximab monoclonal antibodies).  Rituximab was tested in phase 2 clinical trials for MS and was found to be effective.  There is no material difference between Truxima and Rituxan (the original brand name of rituximab).

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

Here is My Question:
I am afraid to have my injection treatment done. I am struggling physically and emotionally, and don't feel like my body can take a 6 hour procedure (prolonged sitting is difficult for me). I am also very concerned about side effects and my ability to return to work right after the treatment. I am already dealing with weakness and fatigue that is limiting my current work schedule. Should I prolong getting the treatment done until a time where I feel better?

Answer:
It is impossible to answer your question without further details and knowing your case. Here is what I can say:

1. It is important with any illness  to try to avoid letting fear interfere with decision making. When I read your question, the stress and anxiety you are experiencing, which is the same thing as fear, is almost palpable. All of us need support to make important decisions. Hopefully your MS team is able to provide this support, if your family and close friends are not supportive.
2. You must be comfortable with a decision and know the alternatives. This will help eliminate the fear.

I assume in your message you are talking about an Ocrevus infusion. Ask yourself and your health team the following questions:

-Why do I need the treatment now? Can I change the infusion date to a more convenient time?
-WHy do I need 6 hours of infusion time? Can I take half the dose (300 mg) with a shorter infusion?
-What can you do differently with this infusion to limit the side effects experienced during the last infusion?
-Are there alternative treatments we have not discussed and what are their risks and side effects?

I find if you ask the right questions and find someone who can provide the answers, it allays many of your fears and anxieties.

Good luck to you.

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