Sylvia found us, and that is the primary learning point of this case study.
Sylvia was diagnosed with MS two months into an internship with an investment bank in London. She probably had an episode of optic neuritis when she was 17, whilst studying for her A-levels. She had transient blurring of vision in her right eye, accompanied by a mild headache behind the eye. Her vision was minimally affected and was back to normal within a week or two. Her general practitioner diagnosed her as having migraine. However, she has the telltale signs of prior optic neuritis when you examine her vision: abnormal colour vision, optic disc pallor, and slowed conduction velocity in that eye on visual evoked potential testing.
Sylvia was then well until she developed weakness in her right foot during her final exams at University. She had difficulty lifting her right foot, and it would catch when she walked, causing her to trip several times. In addition, her left leg felt odd with reduced sensation that was more pronounced in the lower leg. As Sylvia was studying for her exams, she put off seeing the campus GP and waited until she returned home. At this point, the weakness had almost resolved. At her mother’s insistence, Sylvia saw the family GP, who advised her to see a specialist.
By the time Sylvia saw a neurologist at a central London teaching hospital, the weakness had resolved. However, when the neurologist examined her, he detected persistent weakness in her right foot and some altered sensation in her left foot. He didn’t tell Sylvia what he was thinking, but said she needed an MRI of the brain and spinal cord.
Sylvia did not question the neurologist at this stage, as she was excited about her summer ahead. She had a holiday planned with her boyfriend and was due to start a prestigious paid internship at a large international investment bank. Life was good.
Two weeks later, she was called by the hospital’s neuroradiology department, saying they had a cancellation and were offering her the slot if she was free. The problem is that she needed to come in that afternoon for her MRI. As Sylvia had yet go on holiday, she was able to postpone seeing her friends that afternoon and attend the hospital for her MRI. Things changed dramatically two weeks later, when she was on holiday in Greece, she received a call from the consultant neurologist saying her MRI had shown some evidence of inflammation in the spinal cord and brain and that he wanted her to have some additional tests. At no point did he mention the cause of the inflammation.
A week later, on Monday morning, Sylvia was escorted into the daycase ward at the hospital for blood tests and a lumbar puncture. Sylvia had to wait about an hour as the trainee doctor needed some of the blood results before doing the lumbar puncture. The lumbar puncture was uneventful. She remembers feeling a cold sensation on her lower back, some pressure, and then, three minutes later, the young trainee doctors saying it was all done. Sylvia then had to go to another building that housed the neurophysiology department for electrical tests, including a complete set of evoked potentials and central motor conduction times.
You would be wrong to think that Sylvia was a passive recipient of healthcare at this point. Sylvia had immediately Googled spinal cord inflammation, and as a result, she had decided that she likely had multiple sclerosis, and these tests were being done to exclude other conditions and to confirm the diagnosis. Sylvia was a knowledgeable university graduate who had just won one of the most competitive internships in the country. She was an exceptionally bright and capable young lady.
To cut a long story short, when Sylvia saw the neurologist three weeks later, she was surprisingly clear-headed and well prepared when he said she had multiple sclerosis. Sylvia had spent the last three weeks reading up on the condition and was ready for what was coming next. He said she had the relapsing-remitting subtype of MS. He said the visual blurring she had had when she was an A-level student was her first attack, which was supported by the abnormal visual evoked potentials showing slow conduction in the right optic nerve.
Sylvia wanted to cut to the chase and wanted to ask about treatment. He said she would be eligible for several treatments available on the NHS, but wanted her first to go away and understand what MS was before she could discuss with the MS nurse specific therapies. This was not good enough. Sylvia then begged him for a list of the treatments she could have so she could research them. Reluctantly, he provided her with four options: interferon beta, glatiramer acetate, teriflunomide and dimethyl fumarate. He said that his recommendation would be for dimethyl fumarate. When Sylvia asked him about Tysabri and Lemtrada, he said that she would not be eligible for Tysabri as she had only had one MS attack in the last 12 months and that Lemtrada was too dangerous to use first-line and that he personally did not prescribe alemtuzumab.
The issue Sylvia had was that after doing her own research, she had decided she wanted to be treated with Lemtrada or alemtuzumab. Who was this neurologist deciding that alemtuzumab was too dangerous to be used as a first-line treatment? It was at this stage that I received a call from Sylvia’s GP asking if we would be prepared to see Sylvia at the Royal London Hospital for treatment.
When I met Sylvia, she was level-headed, intelligent, and street-smart. She knew about all things MS, having spent several hours a day for months reading and learning about MS. She had read our MS Blog and knew all the arguments for and against treating MS aggressively from the start. She had her whole adult life ahead of her and wanted the best chance of living a normal life despite having MS. Contrary to what the neurologist from St Elsewhere had told her, Sylvia fulfilled the NHS criteria for being treated with alemtuzumab, and she went ahead with two courses of treatment in 2015 and 2016.
What was not mentioned is that Sylvia had a high lesion load on her MRI and had several gadolinium-enhancing lesions on her initial diagnostic scan, including some subtle enhancement of a lesion in her upper thoracic cord—all the more reason for treating her MS aggressively.
From an MS perspective, Sylvia has done well. She has not had any further relapses or new lesions on her MRI, and her brain volume seems to be stable.
Sylvia is now married and has two young daughters. She is a senior analyst in the investment bank where she did her internship. She is the primary breadwinner at home. With annual bonuses, she earns over a million pounds per year. The press and media often call upon her to discuss economic issues. She is an ultra-successful young woman, a super-mum. You would not think she had MS.
This year marked the tenth anniversary of her MS diagnosis and initial course of alemtuzumab. The question is whether she has been cured of having MS. This is where definitions matter and how we define an MS cure.
Although Sylvia has no evident inflammatory MS disease activity (NEIDA), she does have fatigable weakness in her right foot. Sylvia runs half marathons and notices that toward the end of her races and at the end of long training sessions, her right foot begins to drop. Over the last three to four years, the foot drop has started to happen earlier in the race. When Sylvia first began running half-marathons, the foot drop used to occur in the last quarter of the race. She is now noticing it happening from the halfway mark. Is this the first sign of smouldering MS? Or is this simply premature ageing? I don’t know. But if you include ageing or early ageing as part of your definition of smouldering MS, you would say she has smouldering MS.
We don’t usually do repeat MRI scans of the spine to monitor MS disease activity. However, I arranged for Sylvia to have an MRI of her spine, and it is clear that the lesion in her upper thoracic spine had gotten longer, and there is evident cord atrophy at the site of the lesion and in the lower cervical cord. So, based on my current thinking of MS, I would say Sylvia has smouldering MS in an existing lesion in the spinal cord. She is aware of this and expects her right foot weakness to worsen gradually. The question Sylvia asks me whenever I see her is: What can be done to slow or stop this process? She is clearly interested in tolebrutinib.
I am deliberately using Sylvia as an example of alemtuzumab’s ability to do what it can, i.e., stop new lesion formation and prevent end-organ damage. But what it can’t do is stop smouldering MS that is already established in a small number of lesions before treatment. I have many other examples of people with MS who have no evident inflammatory disease activity nor smouldering associated worsening 15 years or more after being treated with alemtuzumab. I think these people have been cured of having MS. I am aware of similar examples in patients treated with AHSCT. I suspect that in time, we will also see some cures after treatment with cladribine. For a more detailed discussion on defining an MS cure, please see my previous newsletter, ‘To cure or not to cure MS, that is the question’ (24-Aug-2023).
I have little doubt that if Sylvia had lived in a different era and had not been promptly treated with alemtuzumab, she would be much worse off than she is now. The counterfactual here would be very different. The only reason Sylvia has done so well and will do well long term is that she is an educated, determined, and self-confident individual who was not prepared to take no for an answer. She knew her rights and made sure she got her MS treated the way she wanted it to be treated.
Sylvia’s case is an example of what we glibly call a ‘social determinant of health’. Usually, we discuss social determinants in a negative sense, i.e. low levels of education are associated with poor outcomes. In this case, high levels of education and self-agency are associated with a good result. Imagine thousands of Sylvias or not-Sylvias across the NHS, and you begin to understand how crucial social determinants of health are. This is why HCPs are so important in counteracting the impact of social determinants of health. If a patient lacks a high level of self-agency, they are relying on us to do what is best for them.
I refer to colleagues who are not prepared to offer and use alemtuzumab and HSCT as the ‘refuseniks’. They are putting themselves and their institutions at risk from legal challenge. When NICE (National Institute for Health and Care Excellence) was created, it was done so through an Act of Parliament. NICE’s primary aim was to eliminate postcode prescribing and variable access to treatments. Therefore, if a therapy has been NICE-approved, the NHS has a legal obligation to offer eligible people that treatment. Thus, in the case of Sylvia, her previous consultant, by denying her access to alemtuzumab, was breaking the law and putting not only themselves at risk of a legal challenge but also their relevant NHS Trust at risk.
You may be asking why neurologists are so paternalistic. Not allowing patients to choose their own treatment is against one of the central tenets of modern medicine. In reality, it is not the neurologist or the institution where the neurologist works who is taking a risk when someone is treated with alemtuzumab; it is the patient who is taking the risk. Don’t they understand this? I think that if you are not using alemtuzumab or HSCT in a proportion of your patients with highly active MS, then you and your centre are not managing MS the way it should be handled in 2025.
Many people with MS who come to me later on the course of their disease, when they are disabled, were never offered high-efficacy therapies, never mind immune reconstitution therapies, early in the course of their disease. Things have changed since Sylvia was diagnosed with MS in 2015, in that most people with MS in high-income countries are now at least being offered anti-CD20 therapies as a first-line therapy. But many are not being offered alternatives to anti-CD20 therapies. It is as if the broader MS community thinks anti-CD20 therapies are the panacea for treating MS. This is clearly not the case, as the majority of people with MS on an anti-CD20 therapy, given sufficient time, will present with smouldering MS.
Therefore, as we approach 2026, several problems persist in MS despite improved overall outcomes for people with MS. These are paternalistic medicine, therapeutic inertia, accepting NEIDA as a therapeutic target, not asking what an MS cure looks like, ignoring smouldering MS, and gaslighting people with MS who bring up the issue of smouldering disease. I sincerely hope things will change in 2026.
Do you agree? How many of you were offered alemtuzumab early in the course of your MS? Do you think we can cure MS? Do you think smouldering MS is a significant unmet need in the treatment of MS? How many of you have smouldering MS? Have you been gaslit when you brought up the issue of smouldering MS?
P.S. Many people were upset by my post about Mary and her condition on Christmas Eve (see Christmas 2025, 24-Dec-2025). I apologise for disturbing you. My timing was deliberate. For me, Christmas and the Christmas holidays are a time of reflection and charity. Putting our heads in the sand or wearing rose-tinted glasses does not stop the suffering of those less fortunate. Relieving others of suffering is part of the Christmas message. In addition, we need to understand how bad MS can be to inform risk-benefit analyses of high-risk treatments early in the disease course. Sylvia knew about the Mary’s of the world when she was deciding on which treatment she wanted. Her decision to be treated with alemtuzumab was to prevent her from becoming a Mary herself.
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Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Queen Mary University of London or Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have any problems, please tell your healthcare professional, who can help you.
