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.