Thursday, 18 September 2014

ClinicSpeak: cognitive MS

Cognitive MS: what is it? #ClinicSpeak #MSBlog #MSResearch

"I have been heavily criticised by MSers and my colleagues for trying to redefine MS as a dementia and for focusing on brain atrophy and cognitive impairment. I am told why be negative and not everyone with MS has cognitive problems. The study below focuses on the entity of cognitive-MS, i.e. the small group of patients who present with cognitive impairment. I have several patients like this in my clinic and when you scan them they typically have large lesion loads and gross brain atrophy. I have always assumed that they have had MS for a long time before presenting. But this is not necessarily the case; for example I look after one patient who had a catastrophic disease early in the course of the disease and now has severe cognitive impairment. The latter is despite alemtuzumab treatment having switched off  the inflammatory component of the disease (relapses and focal MRI activity)."

"How common is cognitive impairment in MS? If you start at RIS (radiologically isolated syndrome) or asymptomatic MS about 25% have cognitive impairment at baseline, this increases to about 30-40% in CISer, over 50% in RRMSer and much higher levels in SPMSers. Interestingly, some studies have shown lower levels of cognitive impairment in PPMSers than SPMSers; presumably because PPMSer tend to have less brain disease and more spinal cord disease."

"What is important to realise that MS causes cognitive impairment and is largely driven by gray matter disease that is not visible on our routine MRI scanners. This is why I am a proponent of early effective treatment to slow down or stop inflammatory disease activity. The latter may not be sufficient to prevent ongoing damage, which is why we are working on neuroprotective strategies."

"Please remember that MS is a preventable dementia. Prevention needs to be stressed. If we treat MS early and aggressively I am confident we will prevent dementia. This is why we need to adopt treat-2-target of NEDA with the aim of preventing end-organ damage. Anything less is unacceptable. MSologsists now have a responsibility for protecting the brains of their patients so that they maintain their cognitive reserves for later on in life when they have to face the ravages of ageing."

"In response to some of the questions on this post you may find the following presentation I gave at ECTRIMS 2013 helpful.""




Assouad et al. Clinical and MRI characterization of MS patients with a pure and severe cognitive onset. Clin Neurol Neurosurg. 2014 Aug 20;126C:55-63.

BACKGROUND AND OBJECTIVE: Cognitive and behavioural symptoms are common in MS, but they are rarely the inaugural and predominant manifestation of the disease. Our objective is to characterize the clinical and radiological features of cognitive-multiple sclerosis(cog-MS), defined as MS subjects who entered into the disease with cognitive symptoms, which subsequently remain the predominant manifestation.

METHODS: We describe the disease course, and clinical and radiological features of 18 subjects with a cognitive form of MS.

RESULTS: Memory loss and behavioural changes were the primary symptoms at disease onset. They remained prominent and led to severe cognitive impairment during disease course. The main associated manifestations were depression, pathological laughing and/or crying, urinary incontinence and gait disturbance suggestive of high-level gait disorder. Motor, sensory or cerebellar abnormalities were uncommon. During disease course, superimposed neurological relapses occurred in 61% of cases. Brain MRI revealed multiple periventricular lesions that were extensive and confluent in half of cases, and a severe atrophy measured as an increase in the third ventricular width compared to age-matched healthy controls. Gadolinium-enhancing lesions were common (72%). The mean diagnosis delay from disease onset was 2 years. A principal component analysis on the neuropsychological results revealed that verbal memory assessment is complementary to global cognitive functioning evaluation in these patients with severe cognitive deficit. Verbal memory deficit was associated with high EDSS.

CONCLUSIONS: cog-MS patients might represent a challenging diagnosis, which needs to be individualized for an early management.

18 comments:

  1. The dictionary lists multiple meanings of dementia and one of them is 'madness, insanity'.

    The other one is 'severely impaired memory and reasoning ability, usually with disturbed behaviour, associated with damaged brain tissue.'

    Most non-medical people associate the word dementia with insanity, and the 'dementors' in the Harry Potter books

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    1. I totaly agree.
      From an academic/scientific POV it may be totally right to classify MS as a Dementia.
      But MSers have to deal with normal ppl everyday and rarely with Academics.

      And the public POV is as indicated by you.

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  2. Prof G,

    From a scan of the ACTRIMS / ECTRIMS conference the aim of achieving NEDA seems to be being discussed / adopted. This is good news. My own experience of Alemtuzumab (in a trial) some eight years ago shows the benefit of treating aggressively and early. Once NEDA becomes the norm, attention needs to turn to (1) those patients where e disease is inactive, but who still have deficit (I'm EDSS 3 as early relapses caused damage to the spinal cord and (2) those patients who have missed the boat with regard to treatments like Alemtuzumab ie they have progressive MS. I hope someone is looking at repair.

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  3. I think the criticism is valid. Your suggestion was done in a cold, academic way, with no regard to the sensitivities of the patient. I'm a youngish man with MS with young children. I see the ravages of MS when I visit my neuro - patients in electric wheelchairs etc. I try to stay positive and exercise / eat well etc. Someone recommended this blog as a source of information for drug trials. What I've really found out is that this disease is way worse that I ever imagined - cognitive issues would be the final nail in the coffin. I don't want to hide from the truth, but your delivery will cause panic / depression among many - we are human beings and had hopes and dreams. I hope in the not too distant future that the blog will move on from just highlighting the horrors of this disease (unemployment, divorce, dementia, incontinence, early death...) and start to give hope to those who have to live with it 24/7. While I have some sympathy with you for how tiring attending international conferences can be, it's way more tiring coping with this disease 24/7. Make sure you never get MS!

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    1. The prime motive behind Prof G's suggestion that MS be classed as a dementia was not only to raise awareness of cognitive problems in MS that have been ignored for far too long but also as there is a big push by the government on dementia this might help in getting more MSers treated early to try and prevent this. This strategy may also have influenced the approval of Alemtuzumab as a first line treatment (when most were expecting approval as a second line treatment).
      When we have good news we report it but I think most who come here appreciate the full range of information here, rather than a bland rose-tinted view of MS.
      The more knowledge you have, the more empowered you are, in my opinion.

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    2. I certainly agree that some of the content here can confronting to put it mildly. It was quite interesting (and somewhat off-putting) to see Prof G deliver this message when he was in Australia though. There is fairly widespread acceptance of NEDA as a doctrine already, and the shock and awe part of the presentation was a sledgehammer to a walnut. However, given that MS is still being allowed to smoulder in the UK, I can understand why the message is pitched this way. There was also a lot of realistic hope on offer as well!

      A lot of people seem to be put off by side effects/risks of DMTs without fully acknowledging the risks of untreated MS. It's hard to make an informed choice without seeing both sides of the coin. It pains me to see people say they won't take anything until it really starts to get bad. I think it may be these people (as well as the regulators) that Prof G is trying to reach.

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    3. I think the majority of MSers fully know the horrors of the disease and on here you are preaching to the converted. Its the neuro's, commissioners and NICE this needs drumming into!

      Key themes told to MSers: Lets wait and see, your MS may be benign / mild. Its too early to start treatment. DMT's are risky. Most people lead a normal life. Your not eligible for that drug. Don't Google MS. MS doesn't kill you and doesn't affect your life expectancy. Lets not forget the heroic stories of rock climbing and marathon running MSers published in glossy charity magazines.

      Some would say this gives us hope. I consider it a disservice.

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    4. Anon 12:15am, you are spot-on!

      The problem that this blog has with its audience of MSers is thus: whilst we all seek knowledge about our malady, the type of knowledge we want and the way we want it presented, depends on our personality type. I have a realist personality and this is reflected in my academic choices and my career: I enjoy evaluating and critically analysing information, so I actively seek relevant literature about MS, irrespective of whether the tone is positive or negative.

      I find most doctors (limited, obviously, to those I've consulted), whether GPs or neurologists, to be extremely paternalistic. They limit sharing their knowledge about probable disease progression, by using the technically true (but extremely convenient and irritating) excuse that each MSers' MS course is different. I was actually made to feel rather foolish at my first consultation post-diagnosis (with the same generalist neurologist who diagnosed me) when he asked whether I had any concerns or questions: I told him that my main concerns were possible future incontinence and cognitive decline, to which he laughed and said that I didn't need to worry about that, adding that I'd probably still be walking in 15 years time! When I asked about treatment options, I was given the standard "wait and watch" response. Luckily for me, I'm not a shrinking violet, so I made an appointment with my GP and changed hospitals so I could be treated by MS specialists.

      I also find that most of the doctors I meet are far more conservative than I, in their opinions about treatment options. Whilst our physicians are unarguably learned, I look forward to the day when patients are given more power over their treatment; and this includes end-of-life decisions, including euthanasia. More doctors need to understand that when faced with a painful, frustrating, debilitating and undignified future, there are more than a few of us who are willing to choose the riskier therapies. I for one would appreciate the legalisation of the type of compassion that we show our pets, so if the riskier therapies result in a negative outcome, I would like to be helped on my way to the never-ending sleep.

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  4. Go to the ECTRIMS ACTRIMS website and http://www.msboston2014.org/index.php/livestreaming
    and watch the presentation by Tim Volmer in Burning debate 3 it is 10min and hear him talk about brain reserve and why he believes in early and "aggresssive" treatment too.

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  5. I totally understand this from a scientific POV.

    But MSers already have to deal with a lot of prejudices already. And Dementia ist the last thing I would like to deal with on top.

    We are already "damned to sit in a wheelchair", "lazy", "depressed", "you name it". If MS will be known for as dementia even more ppl will have a difficult time on how to deal with MSers "he has dementia, you now!".

    Association chain: dementia->alzheimers->derp

    No thanks!

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  6. Very interesting but damn scary for people with MS. A question I'm debating with myself after watching the Volmer/Kapoor debate - and reading the prior post stating that the risk of converting to SPMS is over 80% at 20 years - is should I push for treatment? I was diagnosed with clinically definite MS 15 years ago, had a CIS event 25 years ago. I'm not taking a DMT, I work full-time and have no disability on the EDSS. I think I will but not because of what Dr Volmer said or Professor Giovannoni but what Dr Raj Kapoor said in the debate, when asked what he'd do if he had active MS, and said he'd want aggressive treatment if he had two relapses in the last two years. Well, I have. Ironic given I fall into his 'wait and see' MS category.

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  7. It's important to get through to the regulators and to the people who say 'they won't take anything until it really starts to get bad.'

    But the blog audience isn't just them. It also includes MSers who would take effective therapy if only it was available.

    So perhaps you could balance the depressing stuff with posts on how to stay mentally strong and how to stay as healthy as possible . You may need a counsellor in your blogging team for that.

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  8. Scary slides! I assume that's the point but who is your intended audience? It's not as if we, the patients, have much real choice. We have first line treatments until MS gets obviously worse, when we might meet the criteria for more powerful treatments. Theoretically, your cognitive/dementia argument is really convincing but it doesn't hold any relevance in our real world relationships with healthcare providers. Though I think you might be one of them!

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  9. I don't particularly like to think of MS as dementia due to the fear it evokes. Rebranding it as such could greatly impact on all sorts of things, employment being one of them. I fear loss of cognitive function as much as loss of mobility, more possibly. As a young adult to be told MSers lose brain volume 6x faster than others is sobering stuff.

    Denial is not helpful but given many MSers do not have access to decent DMT’s these posts hit home the hopelessness of the situation. Made harder still knowing early effective treatment could prevent it from happening yet we are denied access.

    You say “we need to adopt treat-2-target of NEDA with the aim of preventing end-organ damage. Anything less is unacceptable. MSologsists now have a responsibility for protecting the brains of their patients”

    I agree with this statement but how is this possible with the current commissioning guidelines and the focus on physical relapses? I’m sat here in the knowledge my brain is probably withering away as I type yet because I don’t have “active MS” I don’t qualify for treatment that could save it.

    Can I ask how you are managing to overcome these constraints in your own practice?

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  10. What would be the best course of action for treating cognitive impairment? I.e. which treatment would be the most beneficial?

    In this concrete case I'm not in an apparent relapse and had one documented attack overall which was in the beginning of this year.

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  11. This is why I am a proponent of early effective treatment to slow down or stop inflammatory disease activity. The latter may not be sufficient to prevent ongoing damage, which is why we are working on neuroprotective strategies."

    "If we treat MS early and aggressively I am confident we will prevent dementia."

    An amazing contradiction.

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    1. Re: "An amazing contradiction."

      Not really, we don't know if early effective anti-inflammatory treatment prevents cognitive decline and/or SPMS. This is why we are working on neuroprotective therapies. It may turn-out that early and aggressive anti-inflammatory treatment is sufficient or we need both; i.e. early and aggressive anti-inflammatory treatment in combination with a neuroprotective therapy.

      Delete
    2. I think I may have asked this before. What is cognitive impairment in MS? How is it defined? How can we recognise we have it? How can we have early treatment if I'm not sure what it is? Apologies for my ignorance.

      Delete

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