Case study: wait to fall pregnant or start a DMT now?
I haven't yet gone on to a DMT as I am trying to fall pregnant. What would you advise?
I was diagnosed with MS in March 2019 following a loss of feeling in my lower body, though my legs, bowels, and bladder still functioned. This led to MRIs on my spine and brain and a lumbar puncture. I lived abroad at the time with private healthcare and had a very responsive neurologist. The MRIs showed an active lesion on my spine and an older lesion on my brain. About four years ago, I woke up a few times in the morning with my legs not working for a moment. Could this have been my first event? The spinal fluid analysis did not show any oligoclonal IgG bands.
I haven't yet gone on to a DMT as I am trying to fall pregnant. I haven't been successful, which may not be realistic at my age (40). Therefore, I am looking to start treatment soon. Your writing talks about treating active MS with high-efficacy DMTs as early as possible.
A key question is whether I have active MS - I have not had any visible activity on MRIs since 2019, and the only symptoms I am aware of are night sweats once or twice a month (typically around ovulation). However, I know that this does not mean the MS is inactive. I read that you think measuring brain loss is an important indicator, but how do I get these assessed?
Would you recommend early treatment with a high-efficacy drug for someone with MS that is not active on recent MRIs? And would your recommendations of which drugs to consider be influenced by the risks of the COVID pandemic?
I now live in the UK and have just been referred to an NHS neurologist through the NHS.
Prof G’s opinion
A diagnostic red flag for me is that your spinal fluid analysis did not show any oligoclonal IgG bands. I would want to check this result and review your history, examination, MRI studies and other tests to make sure you have MS. Approximately 1 in 20 people diagnosed with MS don’t have MS and have another disease (please see ‘Am I sure I have MS?’, 9-07-2021).
The symptoms you describe from four years ago, waking up with your legs not working for a moment, may be related. This is not a typical symptom associated with multiple sclerosis, but it could be a form of sleep paralysis, a so-called parasomnia. Sleep paralysis is simply waking up during REM (rapid eye movement sleep) before the switch, which paralyses your body in REM sleep, has had time to be flipped off. Sleep paralysis is quite common and occasionally affects normal people, particularly when they are very sleep deprived. I had three or four episodes when I was a junior doctor.
Sleep paralysis is described in people with MS, and I have seen several patients with this symptom. The most likely localisation of the lesion would be in the brainstem.
I would not interpret occasional night sweats as being MS-related. This symptom occurs commonly in the general population and doesn’t, based on your description, have any features to suggest a more sinister cause.
Trying to fall pregnant and being on a high-efficacy DMT are not inconsistent. In this situation, we tend to use natalizumab or ocrelizumab. Based on your history, you would not be eligible for natalizumab on the NHS as you would have to have rapidly evolving severe MS, i.e. two disabling relapses in 12 months and recent MRI evidence of disease activity (please see ‘Are you eligible for an MS disease-modifying therapy?’, 16-Nov-2021).
To be eligible for ocrelizumab, we would need to show evidence of disease activity in the last two years, which is why I would want to examine you to see if you have new clinical signs, repeat your MRI of the brain and spinal cord to see if you have new or enlarging lesions and repeat a lumbar puncture to measure your spinal fluid neurofilament levels (NFL). A raised CSF NFL level would also indicate your MS is active.
We are now allowing women to start ocrelizumab and fall pregnant when they do, i.e. in their own time. This is not recommended in the current ocrelizumab summary of product characteristics. We take this approach as most women don’t fall pregnant immediately; it takes, on average, four months to fall pregnant and often much longer than this. Ocrelizumab doesn’t affect fertility and is not teratogenic (affects the developing baby). In addition, the placenta only matures towards the end of the second trimester when it allows antibodies (ocrelizumab is an antibody) to cross from the maternal circulation to the developing baby's circulation. So once you fall pregnant, we delay the next infusion until after the baby's delivery. Even if small amounts of ocrelizumab cross over into the baby’s circulation, they will only cause a transient B-cell depletion.
We are also not concerned about breastfeeding on ocrelizumab. The amount of antibody that crosses into breast milk is small, and this small quantity is likely to be disgested in the baby’s intestines.
Yes, you are correct that time matters in MS, so if you had active MS, I would not want to delay starting you on a highly effective treatment. I have several anecdotal examples of patients of mine who had severe and disabling relapses waiting to start treatment or delaying starting treatment because of family planning or other reasons. Saying this, many women with MS don’t necessarily want to start a DMT until after they have had children and decide not to. The message here is patient choice.
Your question about brain volume loss (BVL) is an important one. We are about to start a study in our centre to monitor BVL routinely in some of our patients to see if it changes our practice and to compare what happens in patients who do not have routine BVL measurements. Brain volume is not measured routinely in clinical practice in the UK.
BVL early in the course of MS is a poor prognostic sign and would nudge us, and hopefully you, towards early and highly effective treatment (flipping the pyramid). You have to realise that DMTs are a preventive treatment. There is little point in waiting for the damage to accumulate before starting a highly-effective DMT.
So my advice for you is to get seen ASAP and to have the necessary investigations to decide which course of action is most appropriate for you.
Dobson et al. Anti-CD20 therapies in pregnancy and breast feeding: a review and ABN guidelines. Pract Neurol . 2022 Jul 8;pn-2022-003426.
Neurologists increasingly use anti-CD20 therapies, including for women of childbearing age, despite these medications being unlicensed for use in pregnancy. Current evidence suggests that women can safely conceive while taking anti-CD20 therapy. Women should not be denied treatment during pregnancy when it is clinically indicated, although they should be counselled regarding live vaccinations for their infant. Women receiving regular ocrelizumab for multiple sclerosis should preferably wait 3 months before trying to conceive. There are few data around ofatumumab in pregnancy, and while there is probably a class effect across all anti-CD20 therapies, ofatumumab may need to be continued during pregnancy to maintain efficacy. We recommend that anti-CD20 therapies can be safely given while breast feeding. It is important to make time to discuss treatments with women of childbearing age to help them choose their most suitable treatment. Outcomes should be monitored in pregnancy registries.
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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have problems, please tell your healthcare professional, who will be able to help you.
Re: "And would your recommendations of which drugs to consider be influenced by the risks of the COVID pandemic?"
Apart from making sure you are vaccinated and on the NHS vulnerable list we don't let COVID-19 affect DMT decision making anymore than other infections and factors. We are now living with COVID-19 as simply another infection.
Hi, your study about measuring grey matter looks very interesting, when does it start and how can people sign up to it?