Here is My Question:
Will 3T MRI pick up lesions not seen at 1.5T? From April 2005-May 2019 I never had a new lesion on 1.5T MRI. And no enhancing lesions have EVER been seen.

But in June 2021 3T MRI was read as 3 new T2/FLAIR hyperintensities characteristic of demyelination disease, 2 left frontal and 1 left parietal though my neurologist says he only sees one new lesion. Clinically, I am stable with no flairs in 15 years. Since diagnosis in 2005 I have been on Avonex, Tysabri(12/06), Tecfidera (9/12), Tysabri(1/19). My JC title was ~3 so I was on a 6 week dosing interval when I restarted Tysabri because I couldn’t take the Tecfidera stomach distress anymore. I had a couple of prescribed Tysabri “holidays” and I was off Tecfidera for ~12 months before restarting Tysabri. And my MRI never seemed to change.

In January 2019 about 3 weeks after re-starting Tysabri I had my first ever asthma hospitalization. In June my pulmonologist added Nucala to my asthma regimen of Advair, Singulair, Allegra and Flonase. In January 2020 I was hospitalized again after getting a cold from my grandson at his Christening. My Advair was increased to maximum dose at discharge.

After my February 2020 Tysabri infusion I decided to stop Tysabri because 1)the pandemic (and I have since known of people who got infected at infusion or dialysis center and some died, Massachusetts was pretty awful early on) and2)possible interference with Nucala which blocks IL5 whereas Tysabri increases IL5.

When I informed my neurologist of my decision and my rationale he responded that MS patients without severe disability were not at increased risk from Covid.

But I am not just an MS patient. I am 64 yo with BMI of 33, severe asthma, type 2 diabetes (HgA1c 5.7 on Trulicity), and hypertension with fair control on 4 meds.

I have always wanted aggressive treatment for my MS but it is not my biggest problem anymore. I also need new knees ( osteoarthritis) and have degenerative lumbar and cervical disc disease and spinal stenosis at C3 S/P ACDF at C5-6,6-7.

My neurologist and pulmonologist finally talked to each other after my pulmonologist took the initiative and they agree that I can be on both Tysabri and Nucala. Really?

My need for any DMT has not been addressed, nor my question about 1.5 vs 3T MRI. And I assume my JC titer is still high though previously I felt more comfortable about that (with increased dose interval) than my neurologist seemed to. He was always pushing Ocrevus which I am leery of with my asthma. I guess Kisimpta probably has the same risk issues without the nuisance of infusions.

My veins are lousy. My insurance company makes me go to a center that is not that slick with bad veins. But I was fully Pfizer vaccinated as of 4/17 so that’s not an issue now.

If I need to be on ANY therapy, what about Kesimpta? I already give myself Trulicity weekly and Nucala every 4 weeks. Another injection is irrelevant to me.

Most of all, why can’t my neurologist see more than my MS? 

OY! I finally got comfortable with stopping DMT Rx and at my neuro visit we agreed I could stay off treatment in setting of stable clinical status and MRI. And then I had this 3T MRI.

Answer:
We’ll, that is a lot to take in!  

I’d be careful reading too much into the 3T v 1.5T MRI comparison. The higher field strength MRI will likely picks up mid pathology (whether it be from prior MS, hypertension, diabetes, we levered cholesterol, etc). Not all lesions are MS lesions and you identified at least a could other health conditions under treatment that can also lead to white matter lesion formation. Your question of whether you need DMT or not at your age is a valid one. Natural history cohort studies demonstrate that the average age where the inflammatory phase stops ranges from 53-55 years.

One option could be holding DMT and reimagine on 3T in 6 months (monitoring for subclinical disease activity). You must exercise caution when stopping Tysabri due to the possibility of rebound disease activity.

I’d suggest asking your neurologist about the need for DMT at this stage of your MS and if there is a comfort level for a drug holiday given your relative stability and age. When making a big decision like this, I suggest that my patients get another opinion from my colleague in MS. It never hurts to have a fresh set of eyes review your disease course.

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

Here is My Question:
Could Ocrevus help manage my MS and inflammatory arthritis?

Answer:
Anti-CD20 monoclonal antibody therapies used to treat multiple sclerosis (examples include Rituximab, Ocrevus and Kemsimpta) are effective treatments for inflammatory arthropathies including rheumatoid arthritis (Rituximab is FDA approved ), psoriatic arthritis and ankylosing spondyloarthropathies (small case series only). 

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

Here is My Question:
My EMG and NCV were negative but my left foot have been numb and tingling for four months and now it’s spread to my shin. My general practitioner says there’s nothing else to do, to just wait it out. Any advice?

Answer:
Persistent numbness of the left foot warrants an evaluation by a neurologist. That is your next step. It is hard to provide further advise or information without completely reviewing your case and, even then, you require examination by a trained neurologist. 

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

Here is My Question:
I have primary progressive MS. I am not currently under any treatment for it. I also have atopic dermatitis and a dermatologist recently prescribed dupixent for me. I got my 1st shot of dupixent last week and though the skin is getting better I'm falling more. Does dupixent affect MS patients?

Answer:
Thanks for your message. Dupilumab (Brand name Dupixent) was approved for the treatment of atopic dermatitis (i.e. eczema)  refractory to topical therapies (i.e. applied to the skin) in 2017 and for adjunctive treatment of asthma in 2018. It is also indicated for treatment of chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis and prurigo nodularis (another skin condition). Dupilumab is a monoclonal antibody therapy that inhibits signaling of 2 cytokines (IL-4 and IL-13) known to be associated with these aforementioned conditions. According to recent posts by the manufacturer (Regeneron) there are over 800,000 people treated with Dupixent worldwide. The current FDA package insert does NOT include any warnings regarding the use of Dupixent in people with multiple sclerosis. 

A review of the literature in PubMed reveals 5 case reports (3 in a single publication) since 2021 of the use of Dupixent in people with MS.

Case report 1 (Laageide L et al. JAAD Case Reports 2021 Sep; 15: 33–35) describes a 34-year-old woman with undiagnosed multiple sclerosis for a year who began Dupixent 2 months before an MS relapse and 4 months before her Multiple Sclerosis Diagnosis. She was not on a disease modifying therapy until after her diagnosis with MS . Dupixent was stopped and her MS was controlled with ocrelizumab.
Case report 2 (Gelato F et al. Dermatol Ther 2022 Oct;35(10):e15740)doi: 10.1111/dth.15740)) describes a 21-year-old with severe atopic dermatitis started on Dupilumab in January 2019 with excellent results. However, after 1 ½ years on Dupilumab treatment he began to experience symptoms of multiple sclerosis (onset July 2020) which was diagnosed in September 2020. Treatment with dupilumab was stopped and his multiple sclerosis was controlled with natalizumab (Tysabri)
Case report 3 (Esposito M, et al. JAAD Case Reports 2022 Nov 5:31:1-5. 
doi: 10.1016/j.jdcr.2022.10.031) describes three people with well-established MS, ages 47, 53 and 60, who received Dupixent for atopic dermatitis while receiving teriflunomide (brand name Aubagio) to treat their Multiple Sclerosis. None of the patients experienced a relapse or worsening of MS symptoms on Dupixent and their MRI scans remained stable. 

The authors of case reports 1 and 2 advised caution when using Dupilumab in people with MS. They hypothesized that inhibition of Th2 responses through inhibition of IL-4 signaling in susceptible individuals may aggravate Th17 mediated immune responses commonly associated with certain forms of autoimmunity including MS. It is important to note that both case reports 1 and 2 describe young, undiagnosed people with MS who started dupilumab before starting a disease modifying therapy for MS. In contrast Case report 3 described no significant adverse consequences of prescribing dupilumab in three older MS patients already on a DMT treatment. 
What conclusions can we draw from these case reports?

1. We need more information before jumping to any conclusions. If you know of anyone with MS who has experienced a worsening of their MS on dupilumab, this should be reported to the FDA through your physician or the manufacturer.
2. I agree with using caution when prescribing dupilumab in untreated, multiple sclerosis patients, particularly young relapsing MS cases. However, we should use caution when we treat people with MS with ANY therapies that can modulate immune responses. Remember, there are many medical conditions associated with different forms of inflammation treated with immune modulators, usually monoclonal antibodies. For instance, we know that TNF inhibitors used to treat rheumatoid arthritis and other rheumatologic conditions are associated with worsening of multiple sclerosis and the FDA has indicated this warning in their labels for all TNF inhibitors.Please note that the conditions treated by dupilumab are all associated with significant morbidity and impairment of quality of life. Unless there is more information available, it would not be rationale to deny this treatment outright to people with MS. 

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

Here is My Question:
I have been having multiple symptoms since I had Covid back in January. I have had extreme fatigue for months that comes and goes. It seems to be getting worse and not better. I have weakness on my left side, especially in my left hand, When I try to do anything that require fine motor skills I have a difficult time. Even washing my hair with my left hand is difficult. I also have been having tremors on that left arm and hand that are worse when I try to do something that requires concentration. I’ve always suffered with headaches/migraines but they have gotten worse since all this started.

I have low vitamin D levels and take 50,000 units a week. My vision is blurry especially when I wake up in the morning. I have numbness and tingling in my toes on my left foot. My PCP ordered an MRI. The MRI was done in February and I have attached the results below. All the symptoms have worsened since the MRI. My doctor said she thought I had Covid brain and I basically have been waiting hopefully that this would go away. I am convinced that it is something else and I’m going to see my PCP this week and ask to see a neurologist. I am 47 years old and I am a registered nurse and a mother of two children. I want to feel better and function like I used to.

Answer:
We are so sorry to hear about the emergence of your symptom complex following your SARs-CoV-2 infection. As you may already know from reports in the press, at least 10 % of people experience persistent fatigue, brain fog (impaired concentration, attention, and memory), paresthesia (numbness and tingling which can be painful) and weakness, all associated with a decline in self-reported quality of life following COVID19 infection. This is more common in women particularly those who experienced asymptomatic or mild infections. To be sure, it is also common for patients hospitalized with more severe forms of COVID19 to experience persistent symptoms, but these symptoms are more easily attributed to the lung or cardiovascular injury from the acute infection. 

The cause of Long COVID is still unknown and under investigation at multiple academic medical centers. Because there is no diagnostic test for Long COVID and the symptoms can mimic other conditions, including Multiple Sclerosis, it is important for people with Long COVID to undergo an evaluation by a neurological specialist to exclude these other conditions. Many academic centers have specific clinics for post COVID patients. There are able to provide an initial evaluation and refer you to an appropriate specialist to exclude other conditions, such as MS. I would call the medical center in your area with the most experience dealing with COVID19 and find out if they offer a Long COVID clinic for an initial evaluation. You will also need to see a neurologist. In the meantime, try to keep up your activity level and get adequate sleep.

Good luck

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

Here is My Question:
I know you can’t give me specific medical advice but I have 2 questions if you have time to answer them.

1. Regarding covid antibodies. I received the Pfizer vaccine about 4 months after my last Ocrevus infusion and the second dose about 3-4 weeks prior to the next infusion. My doctor wanted to test my antibodies because she is not convinced of the effectiveness. She checked the covid antibodies to the spike protein and they were totally negative. Does this have any value or should I assume it was ineffective? Do you ever suggest people get a second vaccine if they didn’t develop antibodies?

2. This is regarding misdiagnosis. I was dx in 2018 and now on ocrevus. I accepted the diagnosis but I still have moments of denial. I am wondering if I have a clear cut dx or one i should second guess. initial symptoms never required hospitalization. started with what I now know as the hug. Around the lower ribs/chest and upper abdomen. IT has always been the worst symptom to the point of almost not being able to breath. I have it controlled on trileptal. I had memory loss of entire situations and had an EEG (negative) and MRI. The MRI shows lesions in all the typical spots including “dawsons fingers”. Other MRIs showed 2 spinal cord lesions. I had negative o bands though. I have major cognitive issues and now on disability. Main things are tremor, hug, memory, word mixing, numbness/tingle, spasms and spasticity, temp issues, FATIGUE. Should I question the diagnosis since I don’t have o bands? It seems to just get worse with no relapse or new lesions.

Answer:
Very good questions and hard to answer. Here are my thoughts:

1. Antibodies against the spike protein for COVID19 is a surrogate marker for either immunization or a prior infection only in people without compromised immune system. A surrogate marker can best be thought of as an indirect marker of an outcome that is more difficult to measure, in this case adequate vaccination. This surrogate marker is not validated as a marker of effective vaccination in people on chronic B cell depleting therapies like Ocrevus. In fact, we know that people on these therapies tend to produce lower antibody responses to vaccinations and some produce no antibodies at all. This does not mean the vaccinations do not work, but it is a cause for concern since you have no easy way to determine if the vaccination is effective. Therefore,we advise that our patients on immunosuppression get vaccinated and continue to wear masks and avoid contact with non-vaccinated people.
2. The presence of CSF oligoclonal bands is not diagnostic of MS and the absence of oligoclonal bands does not exclude a diagnosis of MS. One study correlating CSF oligoclonal bands with brain pathology suggested that some forms of MS are not typically associated with oligoclonal bands in the CSF. I always suggest a second opinion if anyone is uncomfortable with their diagnosis. This is particularly true if you are not being managed by a fellowship trained MS specialist. 

Good luck

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

Here is My Question:
I have had hot flashes, severe fatigue, headaches for days, terrible fatigue, leg pain, shoulder pain, neck pain, blurry vision, and cognitive issues for six months. Neurologist said it was coincidence. Where do I go next? Blood work was normal as was a brain MRI.

Answer:
We are very sorry to hear that you have suffered for so long without answers. While it is not possible to establish a direct doctor-patient relationship on our website, we can help you analyze your problem so that you are at least asking the correct questions.

The most important observation I can make is that your symptoms do not necessarily indicate any neurological problem. For instance, fatigue and body pain are two of the most common symptoms in medicine, both caused by a multitude of ailments. Your only two suggestive neurologic symptoms are blurry vision and "cognitive issues". Blurry vision is easy for an ophthalmologist to evaluate. One of the most common causes for blurry vision these days is dry eyes often exacerbated by staring at computer or cell phone screens for a prolonged period. I am not sure what you mean by, "cognitive issues", but the perception of fogginess, forgetfulness, inability to concentrate and word finding delays ("tip of the tongue phenomenon") are often related to disrupted sleep, stress, anxiety or depression. 
You need to find a good family doctor or internist who will work with you to address your constellation of symptoms in a methodical and organized manner. You must approach your problem with an open mind to possibilities you may not have considered and accept that lifestyle adjustments may be required on your part to help alleviate your symptoms. 
Good luck to you.

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