Dementia another MS mimic. #ClinicSpeak #MSResearch #MSBlog #ECTRIMS2015
“About 3 years ago we started a campaign to rebrand MS a dementia. The reason for this was to get people to think about MS as a cognitive disease that can be disabling long before it causes physical disability. The 50% European unemployment rate in MSers before they become physically disabled is driven by cognitive fatigue, depression and anxiety; symptoms which are all a manifestation of gray matter or cortical disease. When I presented the concept of MS being a ‘preventable dementia’ at the EMA MS taskforce meeting I was chastised by several colleagues. One said to me that it would be unhelpful to focus on the cognitive impact of MS; people with MS don’t need to know this. Another said the term dementia was too stigmatizing. I had to remind this individual that I deliberately used the term ‘preventable dementia’ rather than ‘irreversible dementia’ and that if we treated MS early and effectively we would almost certainly change things. This issue is very timely in view of the emerging data showing that early cognitive impairment is the best predictor of poor outcome in MS and the focus on end-organ damage or brain atrophy.”
“The case study below illustrates the extreme example of MS being a dementia. The authors’ describe a patient who was diagnosed as having Alzheimer’s disease in life who turned out to have a multiple sclerosis at post-mortem. I have a handful of cases not too dissimilar to this case report, who have been referred to me from memory clinics with a diagnosis of possible MS. These patients typically present with cognitive symptoms and when they have an MRI scan they have lesions consistent with demyelination.”
“The upside of the MS dementia campaign is that it may have helped with alemtuzumab getting a first-line license in Europe. I think the EMA rapporteur for alemtuzumab grasped the importance of treating MS effectively and early. If you have active MS why would you not at least want to have the option of the most effective therapy first-line? You can either say yes, no or maybe! It is all about choice. With major caveats that I have mentioned before the 5-year alemtuzumab brain atrophy data presented at ECTRIMS vindicates the EMA’s decision. Let’s hope my cynical hypothesis about reversal of pseudo-atrophy is wrong about the alemtuzumab brain atrophy data and that the data truly reflects optimised brain health from a DMT perspective. I remain concerned that some of the alemtuzumab brain atrophy data is confounded by a proportion of brains swelling as MS-related inflammation returns. This is why I question whether or not the data are too good to be true. As this is a hypothesis we can test it with further data analysis or a new deep phenotyping study.”
“After the EMA MS taskforce meeting one very prominent neurologist told me a personal anecdote. In his very eminent career he had looked after numerous patients with MS who became demented and eventually ended up living in nursing homes, but had ended up being very happy and content with their lives due to their dementia. In his opinion they had ended-up with a very good quality of life. He felt the graph I had shown correlating poor quality of life with disability did not tell the whole story. He made the point that if he had treated these patients ‘aggressively early on’, they way I had proposed in my talk, that several of them may have died of adverse events from the treatment and that these patients would have been denied the right to live out their lives albeit in a nursing home with dementia. The latter is an interesting take, albeit an old one, on the doctor-patient relationship. I wonder if MSers today would relate to this attitude?”
“The following are the results of the survey we ran on this blog to support our campaign. Although the survey is not ‘scientific’ they tell a compelling story.”
Tobin et al. Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings. Mult Scler. 2015. pii: 1352458515604382.
BACKGROUND AND OBJECTIVES: We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology.
METHODS AND RESULTS: Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex.
CONCLUSIONS: Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry.
CoI: multiple
This idea is similar to dog euthanasia in case of early cancer. Don't amputate the leg, kill the soul after you give cookies, so it will die happy.Given that that neuro had never had dementia and has never been in a nursing home, I guess he shouldn't praise being crazy, unaware of self and abandoned.His opinion made me sad and mad.
I too was astonished at his remark.
Truly remarkable. Should ask him what could this person have been had he not been demented and in a nursing home? Given the choice, who would seriously want to live out their years in a nursing home! Typical behaviour from many many in medical profession. Luckily, Prof G is an advocate of real quality of life.
If your hypothesis is correct, that the apparent normalised brain atrophy 5 years post Alemtuzumab is actually the result of the brain swelling with MS related inflammation, why then are there no MS-related clinical signs? And do you think then that it is inevitable that patients will soon start displaying new clinical MS symptoms?
Re: "And do you think then that it is inevitable that patients will soon start displaying new clinical MS symptoms?"The data presents the average; hence you only need a small proportion of the group to have subclinical activity, which would would be enough to swell the brains and skew the average towards normal. As this cohort of MSers have early MS they have cognitive reserve and can probably deal with subclinical activity. Please note I am playing devil's advocate here; I don't want to simply accept these results and raise false expectations if down the road alemtuzumab treated MSers run into problems. I have framed this as a hypothesis and I suggest we take a group of alemtuzumab MSers who are NEDA-4 and interrogate them to see if we can find any evidence of subclinical MS activity; I refer to this as deep phenotyping. We would need to compare them to MSers on other DMTs or no drugs at all to see. Results of a study like this will convince me and hopefully get more neurologists to adopt early induction treatment.
Prof G, doesn't the data previously mentioned on this blog which shows that very significantly fewer than expected people progress to SPMS provide at least some real evidence that perhaps atrophy is genuinely normalised rather than the pseudo-atrophy theory? I know it's good to get more and more data to convince the doubters, but perhaps this data should also be actively marketed to neurologists and patients so that they can make a rational decision (obviously with the negative side-effects fully explained)? My experience of neurologists (prominent MS specialists at that) is that they refer to studies done on old drugs a long time ago to tell you that they have no effect on conversion to SPMS and just there to control relapses. Surely they need more updated info! Or perhaps they just have completely different views of MS..frustrating for patients I think, especially those that do not read independently – which is most of them!
I think you generalise when you say MS patients do not read independently. I think you may find they do and they make their own choices about DMTs. They just get on with their lives and don't believe every press release. Some don't even have a neurologist.
Sorry I disagree. Most people do not read into their illness. I know a few young MSers who do not read into it at all. They inherently trust their neurologist, which may not neccessarily be a bad thing. There is very little indpendent reading beyond very generic marketing/informational type of basic literature. From the total MS population, the amount who read blogs like this is probably negligible.
"If you have active MS …" : What is the definition of 'active MS'?You must have answered this question earlier but it's important.
Re: "… Active MS"Active MS refers to having had clinical attacks, or relapses, in the last 24 months or MRI activity (Gd+ lesions and.or new T2 lesions) in the last 12 months. In essence evidence of recent ongoing focal inflammation (lesions). These definitions vary, but typically refer to the inclusion criteria that are in general use for RRMS trials.
This post does not clarify how long the patients lived before they became so demented they ended up in care homes. The prominent neurologist may be right about the adverse effects of early treatment. This argument can be spun both ways.
And there is "live" even if you have no more "self-awareness"? Please it is obvious that the life we MSers changed since the first DMT emerged. And I'm sure that will change even more when the DMT's highly effective start to be administered early, at the beginning of the disease as well as really effective treatments start serwm produced for progressive forms … I just hope the thought of saying "Eminent Dr." does not propagate in medicine and for science as a whole, that solves not throw in the towel for everything, "Oh okay he has cancer, that he has Alzheimer's, no way, will die anyway, so let us leave it there in enjoying corner his illness "….
If you have SPMS you probably lived a half decent life within the constraints of MS. If you suffer serious complications from DMTS, that is taken away from you. It depends on the answer to Anon 7:42. Not all MSers lives changed with the emergence of highly effective DMTs.
There is some study looking for patients treated with these DMT's less potent as Interferons and Glatiramer Acetate and Dementia?
At what age are people diagnosed with MS related dementia? Same age as Alzheimer's? I assume MS had not been diagnosed before the onset of dementia? I know that memory, mood and cognitive fatigue are my biggest problems now. Only 42, but ignored for years by GPs… GPs are a big big problem with MS diagnosis in the UK.
"GPs are a big big problem with MS diagnosis in the UK"I agree with this. My GP assumed my constant horizontal double vision was part of benign vertigo ! I am very worried for myself and others.
You're lucky if you see your own GP. Gone is the day when you could discuss your illness confident that they know your history. If you have a chronic illness the ten minute slot is not enough time to read your notes. It doesn't matter who gives you an antibiotic for your UTI, but try discussing anything about your long term care. GPs are stretched too thinly and there are consultants in hospitals getting the specialist nurses(not just MS) to see you whilst they look after their private patients.
GP surgeries are now just full of locums – typically just a shift for them, here today, there tomorrow. There was a time when GP was like a family friend who knew your history. I truly believe the service has now diminished as locums just cannot link your history together in the short amount of time they have.
And how many of 'his' patients were not happy, had a poor quality of life, and did experience adverse events because they didn't have treatment options.How dare he decide what my quality of life is. How patronising, offensive, dismissive, bullying, and I'd better stop before I get really cross.Please tell me that this eminent neuro is happily on his way to retirement!
I agree with the above; a patronising attitude always sets my teeth on edge. Thank you for this blog which informs and helps to equip us to make decisions about our treatment options.