Here is My Question:
I am 70 and Negative for JCV Virus. My doctor wants to take me off Tysabri (I have been on for approximately 13 years. He wants to take me off cold turkey. Is that Safe? Will I experience significant breakthrough symptoms? Should I be weaned off rather than cold turkey? Any suggestions would be so helpful. 

Answer:
This is a difficult question to answer without more detailed information. To begin with, it is unusual for people who are 70 to still be taking disease modifying therapies. Let me give you some information to help you discuss this question with your MS doctor. Rebound relapses after stopping Tysarbi,

1. Tend to occur in younger relapsing patients, usually under the age of 60, if not even younger. It is far less common in older patients
2. Tend to occur in patients with evidence of inflammatory activity prior to starting Tysabri. This means a verified relapse or enhancing MRI activity prior to starting Tysabri. 

None of the currently approved disease modifying therapies have been tested in controlled trials that included people over the age of 60. Older patients more commonly experience relatively stable or secondary progressive MS without relapses (SPMS without relapses), stages of MS either not responsive to DMTs or without evidence that DMTs are required. Perhaps this is why your neurologist is stopping the Tysabri. If you are worried about a rebound relapse, you can always ask him for a single infusion of anti-CD20 therapy (Rituximab 100 mg, Ocrevus 300 mg or Briumvi 150 mg) within 2-3 months of stopping the Tysabri to prevent a relapse after excluding the remote possibility of pre-symptomatic PML with a repeat MRI of the brain.

Good luck

Revere P (Rip) Kinkel, MDProfessor Emeritus
Neuroscience Department
University of California San Diego

Here is My Question:
Hi there, so I passed my NREMT and am now able to get certification to work as an EMT. I am not in shape so I've been working out gently. I was diagnosed with MS last year and during the summer last year I started having difficulty walking. It was like tingling like my leg fell asleep except it hurt and would only stop if I stopped walking or sat down (sometimes it didn't always work then). I've noticed that I have issues with going up stairs on a daily basis and walking at a consistent pace. It's not that I feel those tingles though, it's just painful to move. All of this being said, I would really like to see myself move past this and do something I want to do by being an EMT. Even if I condition my body for the job, is there any reason I should not pursue this job?

Answer:
I am not able to determine if it is feasible for you to perform the duties of an EMT without knowing a lot more about you and your condition. If you have the ability to see a rehabilitation medicine (a Physiatrist) specialist where you live who has expertise in MS, this would be a useful person to see for assistance. By all means reach out to your MS specialist for advice, if you have one, or discuss this issue further with your current neurologist. Neurologists see people with mobility issues on a daily basis and are trained to assist them in meeting their goals of care, including maintaining their desired employment if feasible.
Good luck

Revere P (Rip) Kinkel, MDProfessor Emeritus
Neuroscience Department
University of California San Diego

Here is My Question:
I'm an MS patient who's currently being treated with Tysabri. I've been reluctant to switch because I'm prone to side effects and was relived to have finally found a drug that allowed me to have a decent quality of life. I'm JCV positive and have been for some time, so my neurologist wants me to switch to Ocrevus (though we extended my dosing times which lowered my JCV numbers). Here are my questions. Am I taking too much risk trying to stay on Tysabri with positive JCV numbers?~Are there any doctors who would continue to prescribe Tysabri to someone who's been on it for over a decade and is JCV positive? Thank you!

Answer:
​This is a tough question that we have answered many times on this site. The decision really comes down to relative risk and individual choice.
The main risk factors for PML in people on Tysabri for MS include

1. JCV index positive, particularly JCV index > 0.9
2. Prior chemotherapy either for MS or cancer
3. Duration of treatment > 2 years

Other risks may include older age (> 65) and low weight (< 60 kg) but these risk factors are not listed in the physician drug reference reviewed and accepted by the FDA.

The risk factors for continued MS relapses are younger age (< 50) and relapses or MRI activity in the year prior to starting Tysabri.

We have registry data suggesting a markedly reduced risk of PML in MS patients taking Tysabri on extended dose intervals (usually 6-8 weeks between infusions) but these patients were not separated by JCV index status. A study run by the drug maker of Tysabri did show equal effectiveness of every 6-week infusions versus the usual every 4-week infusions as long as participants received every 4-week infusions for at least a year before extending the dosing interval.

We also know that stopping Tysabri is associated with approximately a 30 % risk of relapse, so we always give a single cycle of anti-CD20 infusion (i.e., Ocrevus or rituximab usually) within 8 weeks of stopping Tysabri to prevent relapse. 

Overall, if people have been stable on Tysabri for many years (like you), are JCV Index positive, and are over age 55, we will often recommend a single infusion of Ocrevus or Rituximab after stopping Tysabri to prevent rebound relapses and then monitor them off of all treatment for any return of disease activity. Before giving them the infusion of Ocrevus or Rituximab, we make sure there is no evidence of presymptomatic PML. We only continue the anti-CD20 therapy infusions or injections in the listed circumstance, if people show a return of disease activity following the initial infusion

I hope this helps. Please discuss these thoughts with your MS specialist

Here is My Question:
Hello,
I'm curious to know what labs are taken and looked into prior to next round of Rituximab (or b-cell depleting medication in general)? What is normal/concerning? What is tested? What will be something that would post pone infusion? Etc.

I hope I'm making sense. Thanks in advance

Answer:
Excellent question. The FDA approved package insert only requires labs prior to the first infusion and includes a Hepatitis B serological profile and immunoglobulin levels. Since we know that treatment may cause immunoglobulin deficiency and other abnormalities in blood cell profiles and these deficiencies increase the risk of infection, most centers routinely obtain a complete blood count and differential (CBC with diff) and Immunoglobulin levels before each infusion. 

Most centers also check total CD19+ B cell counts before every treatment, although this is probably only necessary prior to the first treatment if you plan to receive infusions every 6 months according to the FDA approved dosing interval. If you plan to shift to extended interval dosing, an increasingly common practice to avoid prolonged B cell suppression, then you should get B cell counts or better yet, complete B cell subsets, prior to every infusion. This could then be used to guide when to repeat infusions.
​
So to recap, minimal labs prior to every infusion are CBC with diff and Immunoglobulin levels, particularly IgG levels.

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

The relative safety of surgical vs medical pregnancy termination depends on the stage of pregnancy. Generally, early termination, which is part of the indication for drug-based abortion, is very safe with drug-based abortion (i.e. mifepristone plus misoprostol). Medication abortion is indicated up to 77 days (11 weeks) after the first day of your last menstrual cycle. There are some contraindications to medication abortion including chronic corticosteroid usage and ectopic pregnancy but most of these contraindications are rare. You should definitely talk to your primary care or OB/GYN doctor about your options before making any decisions.

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

Here is My Question:
I had an attack in November - a single thoracic spinal lesion was found and apparently lots of bands in my spinal fluid. No brain lesions. This was immediately following a round of IVF.

Now being treated with Tysabri. My neurologists feel sure that this is early MS, but another neuro thinks it could very well have been a one time event. Two questions? What is the likelihood that I will have another attack especially now that I’m on a DMT? And do you think this could have been caused by the drugs in IVF stimulation medications?

Answer:
By 2017 diagnostic criteria (not by prior criterion), you currently satisfy the minimum requirements for a diagnosis of multiple sclerosis.  Your risk of relapse is very low on treatment with natalizumab (Tysabri). A recent case control study from Denmark suggests that assisted reproductive technologies (including IVF using hormonal stimulation) do not increase the risk of developing Multiple Sclerosis. 

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

Here is My Question:
My son's neurologist recommended Ocrevus for PPMS 6 weeks ago. No reply from insurance company. Is this delay normal or cause for concern?

Answer:
Delays in obtaining approval for an indicated MS treatment are often caused by understaffed, overburdened Doctor's office personnel not having the time to respond to insurance requests to provide prior-authorization documentation. Contact the doctor's office to see if they've received any requests from the insurance company for further information. If they have not, contact the insurance company to learn the status of the request.

Good luck

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

Here is My Question:
I am taking the mini-pill and forgot to take one the previous day (took the two as soon as I realized today) Is it still okay to take the morning after pill? Additionally I am still on my period this month. Thank you in advance for your assistance.

Answer:
If you miss your regular oral contraceptive pill by 24 hours and double up on your next oral contraceptive pill (take 2 pills), you do not need the morning after pill. I would check with whoever prescribed your oral contraceptive. Some people are on other medications which decrease the efficacy of oral contraception, and if this is the case your doctor may have other recommendations.

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

Here is My Question:
Can I talk to a doctor online. I have severe agoraphobia?

Answer:
Most doctors are still doing video visits . The only requirement is that you must be present in the same state as the doctor. For instance, a person in Texas cannot have a video visit with a doctor in California, but a person typically living in Texas who is visiting California can have a video visit with a California doctor.  Most doctors also want a referral from your regular doctor and would benefit from your medical records and images, if they are available. 

Formal telemedicine is organized differently and allows doctors to participate in care outside of their state. Far fewer doctors participate in these nationwide networks.

Video or telemedicine visits cannot accomplish as much as an in-person visit. The examination is lacking and that is a drawback in Neurology.

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

Here is My Question:
Would the serum band of 4 be considered MS?

Answer:
I believe you are referring to a lab report on the presence or absence of oligoclonal bands in the CSF and Serum sample collected at the same time.

These reports sometimes provide the number of IgG bands in both the serum and spinal fluid (CSF) using a technique called isoelectic focusing. When we say a person has oligoclonal bands in their CSF, we are referring to bands without a homologous band present in the serum sample. Therefore, the presence of serum bands has no relevance to the diagnosis of MS. Only the presence of spinal fluid (CSF) bands without matched serum bands are relevant to the diagnosis of MS.

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

Here is My Question:
Does MS causes burning mouth syndrome?

Answer:
It would be extremely unusual though possible for MS to directly cause anything akin to burning mouth syndrome. Many of the causes of burning mouth syndrome are more common in MS patients, so indirectly this syndrome may be seen in people with MS. These causes of burning mouth syndrome include nutritional deficiencies, medications (including those causing dry mouth), Sjogren's disease and some viral illnesses.

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

Here is My Question:
Is MS a progressive disease?

Answer:
This is an excellent question. I think many people tend to use imprecise terminology when describing clinical features of MS. Let me give you a framework for many of these common terms.

1. Relapse: This refers to new or worsening symptoms caused by new inflammatory activity. The reason we often argue about whether new or worsening symptoms are caused by new inflammatory activity (i.e. not a relapse) is because we often cannot prove, through history, exam or even MRI that there is evidence of new inflammatory activity and there could be other explanations for the new or worsening symptoms.
2. Remitting: This only means that new or worsening symptoms stabilize and improve to some extent compared to their peak severity. It does not imply a return to normal and the improvement can take up to 6 months or longer.
3. Stable: We use this term to imply no evidence of relapse or disease progression over a given interval of time, usually yearly intervals.
4. Progressive: This refers to continuous worsening in neurological function over an interval of time usually too long to be considered a relapse. Most neurologists use an interval of 6 or 12 months to define this continuous worsening. This means that progressive disease can only be defined in retrospect. Furthermore, people with progressive disease will often stabilize without improvement for periods exceeding a year prior to demonstrating further progression. This feature was documented years ago by Dr Donald Goodkin. Often when we see continuous, rapid, and dramatic worsening over shorter intervals (usually 3 to 6 months), we also see dramatic evidence of inflammatory disease activity on MRI, a feature that is atypical for progressive disease. These people are often younger than typical progressive patients as well. Most progressive patients are above the age of 45 at diagnosis.

The main problem with the casual use of these terms by both lay people and professionals is that they often are used for other purposes. For instance, the fact that MS is a chronic disease (i.e. it never disappears completely) is often confused with the concept of disease progression. While many people do develop progressive disease as defined in # 4 above, at least 25 % or more never develop evidence of progressive disease despite the chronicity of their condition. 
I hope this helps

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

Here is My Question:
Now that Ocrevus has been out for a while and we have more information, do you think it is more effective than Tysabri? I recently read a study saying Ocrevus and stem cell transplant were similar in efficacy. The authors cautioned that there was only 3 years of data. Still, pretty impressive. Also, what is the risk of jc positive person transitioning from Tysabri to Ocrevus in regards to PML? I know there should be a MRI before starting Ocrevus.

Answer:
There are no randomized head-to-head comparisons of Ocrevus and Tysabri adequately powered to answer your question. Smaller observational comparisons suggest little difference in comparative efficacy in people with relapsing remitting MS. Both therapies compare well to the efficacy of Hematopoietic Stem Cell Transplant (HSCT), but with far fewer risks and side effects. 

Many JCV positive people with MS eventually switch form Tysabri to Ocrelizumab (Ocrevus), Rituximab, Ofatumumab (Kesimpta) or Ublituximab (Briumvi); in fact, the most favored treatment option after discontinuing Tysabri is treatment with one of these anti-CD20 monoclonal antibody therapies. Before switching it is important to exclude pre-symptomatic PML with a repeat MRI scan. Switching to an anti-CD20 therapy also dramatically reduces the risk of a rebound relapse after stopping Tysabri.

Revere P (Rip) Kinkel, MDProfessor of Neurosciences
Director of the Multiple Sclerosis Program
University of California San Diego​
#multiplesclerosis #MS #Ocrevus #Tysabri