Here is My Question:
I am 29 years old and about to start my treatment in one month, and I have the JC Virus. Does Rituximab have known side effects after several months or years of use? Also, if I ever decide to stop my treatment, will it severely impact the lesions in my brain, or will I get faster lesions after getting off of treatment?

Answer:
In the short term there are few risks other than infusion reactions (which are usually mild to moderate and improve after the first infusion), rare case of colitis (inflammation in the bowel), rare cases of herpetic reactivation (usually shingles), and an increased risk of upper respiratory tract infections (less commonly pneumonia) and some other common treatable infections. These risks generally increase with the number and duration of treatment infusions, the age of the patient, the degree of neurologic disability and the presence of prior immunosuppression or other co-morbid medical conditions. There certainly have been cases of PML in people on anti-CD20 therapy when no other cause of the PML could be found but this is very rare.

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

Here is My Question:
Are there any tests that can indicate if a person will develop MS even if they have no symptoms, but has multiple family members with MS?

Answer:
The question is, How can you determine if you are at high risk of MS before you develop symptoms or exam findings?

For many years, we have known that people with MS often exhibit potentially prodromal symptoms, sometimes more than a decade before a definite diagnosis can be made even using the newer diagnostic criteria for MS.  To my knowledge the first prospective study to report potential prodromal symptoms was the optic neuritis treatment trial (ONTT) designed and led by Roy Beck and first reported in early 1990's. A major secondary goal of the ONTT was to determine risk factors for a person to develop MS after an isolated episode of optic neuritis (ON). As you may know, optic neuritis is a common first symptom of MS but only 50 % ( a flip of the coin) of people experiencing optic neuritis develop MS; the investigators want to find out how to better predict the risk of MS after ON.

​There have been many reports from this study over the years of the predictive role of brain MRI findings in determining a group with a higher risk of developing MS. What people often forget is that the investigators also asked patients presenting with acute optic neuritis  (an no knowledge of the MS) if they had ever experienced prior neurological symptoms before this episode of optic neuritis. It turned out that many people did experience prior symptoms such as paresthesia (i.e., unusual sensations), vague cognitive complains, unusual episodes of fatigue, and subtle urination problems to name a few, that were either not investigated or attributed to another cause. When the investigators lumped these symptoms together-calling them "vague neurologic symptoms"- and continued to follow patients over the years, they discovered that these "vague neurologic symptoms" were statistically associated with the future development of MS. 

Fast forward to the present and investigators have developed a more urgent interest in learning how to identify people with MS prior to the onset of symptoms by using a combination of prodromal symptoms, family history and genetic risk factors, and various biomarkers. The main motivation for learning to identify people with presymptomatic MS is the increasing number of studies suggesting that earlier initiation of disease modifying treatments leads to improved long-term outcomes. Many of these studies are in early stages of development and will want to recruit people with a family history of MS, since a positive family history already increases the risk of MS by a percentage based on the relationship of the relative(s).  Stay tuned for more information.

Great question by the way
Revere P (Rip) Kinkel, MDProfessor Emeritus
Neuroscience Department
University of California San Diego

Here is My Question:
Hello! I'm a 26 year old female who's been living with multiple neurological symptoms for over 10 months now.

I've had multiple brain MRIs (done on 12/23, 3/24 and 7/24) along with MRIs of my entire spine (lumbar done on 3/24, cervical done on 3/24 and thoracic done on 7/24). All MRIs were performed with and without contrast. All of my imaging has come back normal. I've also been tested for Lyme, syphilis, HIV, bartonella, and SSA 52&60(RO)(ENA)AB IGG. All the results for these labs came back negative as well.

I had a lumbar puncture done in March of 2024 which came back positive for 11 oligoclonal bands in my csf, but none found in my serum.

To date, I've been collecting neurological symptoms like Pokémon. Mainly, I deal with left sided facial numbness (onset: 11/3/23), numbness/tingling in my extremities (onset: January 2024), muscle spasms/twitching (onset: February 2024), weakness and stiffness of my left calf (onset: mid February 2024), heavy feelings/pain in my legs/back when walking for too long (onset: March 2024), and watery bowel issues (onset: March 2024).

These symptoms usually come and go several times throughout the day. They all started out as hardly noticeable, but have become more prominent with time. I think some symptoms have improved slightly with time (facial numbness, bowel issues). Other symptoms have gotten progressively worse (twitching, endurance while standing and moving around). Some symptoms have evolved a bit (calf weakness/stiffness is still present, but now it feels like my left knee is more affected). I take 20mg of amitriptyline for the numbness/tingling each night, and it caused this symptom to disappear for two months. It's been creeping back in during the afternoon and evenings though, so I suppose this symptom is getting worse as well. There are other symptoms, but to be honest, I can't keep track of them all anymore.

I know that MS could be the most likely culprit for what's happening to me. I also know that I don't meet the McDonald criteria for an official diagnosis. Despite my clear imaging, I'm still scared of having PPMS. I've yet to have a true attack or relapse that I know of. The lack of visible lesions worries me as well, since I know that PPMS patients tend to have a lower presence of inflammation in their MRIs compared to RRMS patients.

I've read stories of people suffering with chronic symptoms for years before finding lesions on their brain and spine and getting a PPMS diagnosis. I'm afraid this exact scenario could happen to me.

Does my story sound like MS to you? I know I don't present like a textbook case, but I'm not sure what else could explain everything that's been happening. In addition, would anyone be able to clarify whether my case could be RRMS after all? I've yet to find anyone with a similar presentation/diagnostic story outside of PPMS patients. I'm scared of the possibility of having progressive MS so young. I know it's exceedingly rare, but my story already feels rare compared to many MS cases in my age range. Having RRMS feels like a long shot, but I'm scared of things progressing further.

My current neuros have differing opinions. My first neuro said I most likely have MS based entirely on the results of my spinal tap. He even wrote me a prescription for Kesimpta. My second neuro doesn't think I have MS, and wants to test for every possible suspect. Being in limboland for so long has been mentally excruciating, and I just want to know what's happening to me, and if it will ever be able to stabilize or get better.

Answer:
​The presence of a large number of oligoclonal bands (greater than 4) in the spinal fluid that are not present in a matching serum sample is an abnormal finding that usually requires explanation (see below). However, it is not diagnostic of multiple sclerosis without further confirmation.
The first thing you must do is confirm that the oligoclonal bands that were reported in your CSF were distinct from those present in a matching serum sample. It is not uncommon for patients to be referred to us because of a spinal fluid report stating, "oligoclonal bands present in the CSF", only for us to discover that the small print states, "matching bands observed in the serum". Sometimes, the small print is excluded from the report sent to us and we must contact the lab for confirmation.
Assuming the analysis did find 11 oligoclonal bands in your CSF that were not present in a matching serum sample, there are several possibilities:

1. The OCBs are a product of an infectious (viral infections, Borrelia, and syphilis most common causes) or non-MS related inflammatory process (sarcoidosis is most common) that is still active; this is more likely if other abnormalities were observed in the CSF
2. This could represent prodromal findings of multiple sclerosis or MS primarily confined to cortical gray matter. Standard clinical MRIs are not able to image MS involvement of the cortical gray matter, a common area involved by MS even early in the course of the disease.
3. The oligoclonal bands are a residual effect of a prior infection, perhaps mononucleosis, that resolved. This may indicate you are at risk of MS

I would recommend the following:

1. Check on the accuracy of the prior oligoclonal band report as mentioned above
2. Assuming the report was accurate, if the prior spinal fluid analysis was done over a year ago, you may want to repeat the lumbar puncture. Oligoclonal bands that disappear are unlikely to be caused by a chronic condition such as MS or other chronic infectious or inflammatory conditions
3. If the CSF continues to show oligoclonal bands in high numbers (greater than 4 bands that are not present in the matching serum sample), you may need a high field MRI, preferably at 7 Tesla but a 3 Tesla scan with double inversion recovery sequences may help, to see if there is evidence of cortical  gray matter involvement. This type of MRI scan is not done routinely and may require a referral outside of your region.

You should take this information to your current neurologists to discuss further .
Good luck

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