Monday, 17 June 2013

Rebranding MS a dementia (3): Cognitive impairment in asymptomatic MS (or RIS)

Cognitive impairment may begin before the first attack of MS. #MSBlog #MSResearch

"This is an old post that needs more air time. It shows that over 25% of RISers, i.e. people who are asymptomatic and are found to have lesions on MRI compatible with demyelinating disease have significant cognitive impairment (pre-MS). This and other studies underpin the observation that one of the major hidden burdens of MS is the impact it has on cognition. Fortunately, most of you won't notice early cognitive impairment as your brain has the remarkable ability to compensate for damage. The consequences of this adaptation is increased energy consumption, concentration and attention to complete  the task. MSers are easily distracted and find it difficult to multi-task cognitively. Compensating with cognitive impairment is associated with mental fatigue. It simply takes MSers, CISers and RISers with cognitive impairment more mental effort to complete the same mental task as a 'normal person'."

Epub ahead of printAmato et al. Association of MRI metrics and cognitive impairment in radiologically isolated syndromes. Neurology. 2012 Jan.

OBJECTIVE: To evaluate cognitive changes in a cohort of radiologically isolated syndromes (RIS) suggestive of MS and to assess their relationship with quantitative MRI measures such as white matter (WM), lesion loads, and cerebral atrophy.

METHODS: We assessed the cognitive performance in a group of 29 subjects with RIS recruited from 5 Italian MS centers and in a group of 26 patients with RRMS. A subgroup of 19 subjects with RIS, 26 patients with RRMS, and 21 healthy control (HC) subjects also underwent quantitative MR assessments, which included WM T1 and T2 lesion volumes and global and cortical brain volumes.

RESULTS: Cognitive impairment of the same profile as that of RRMS was found in 27.6% of our subjects with RIS. On MR scans, we found comparable levels of lesion loads and brain atrophy in subjects with RIS and well-established RRMS. In subjects with RIS, high T1 lesion volume (ρ = 0.526, p = 0.025) and low cortical volume (ρ = -0.481, p = 0.043) were associated with worse cognitive performance.

CONCLUSIONS: These findings emphasize the importance of including accurate neuropsychological testing and quantitative MR metrics in subjects with RIS suggestive of MS. They can provide a better characterization of these asymptomatic subjects, potentially useful for diagnostic and therapeutic decisions.

"The results of this study are not unexpected. In the earliest stages of MS prior to the first clinical attack there is evidence of cortical or gray matter involvement that is associated with cognitive impairment."

"As a corollary to this; I have seen a few MSers presenting with cognitive impairment as their only complaint that on work-up proves to be due to MS. Although this is rare is does occur and indicates that gray matter disease is a problem."

"The implications of this study will be troubling for MSers. How much hidden cortical function is lost before my first attack and will I get this function back if my MS is treated with a DMT?"

"You have to remember that the aim of DMTs is prevent further damage; full recovery of lost function is unlikely. Despite this the brain is very plastic and adapts well to damage so most MSers won't notice a problem. To detect this damage you have to have detailed neuropsychological assessments."

"This data further argues for aggressive suppression of MS disease activity, i.e. ASAP after diagnosis. Hopefully this will prevent or at least slow down further damage to the gray matter and cognition. The question is who would be willing to have DMTs  if they have never had an attack to be able to allow neurologist to make the diagnosis of MS? May be our diagnostic criteria for MS need revision?"


  1. Re 'who would be willing to have DMTs if they have never had an attack': an MRI won't happen till there has been an attack, so nobody will know about the RIS and the willing/unwilling question will not come up at all

  2. That is incorrect. I never had an attack, but had an MRI for something totally unrelated. They saw something that was suggestive of MS. But 6 months of intense testing at NIH and multiple MRIs showed NOTHING more than that little original suspect spot. It has been ten years. And nothing. But the massive anxiety associated with this whole ordeal...

  3. This certainly makes the case that neuros should be very very cautious about declaring anybody benign. But does it also mean that they should be very careful about declaring anybody "stable"? That is, if I'm on safe little front line DMT and my MRI is showing no there really no activity? Should I pursue more aggressive cognitive testing to be sure? Or more aggressive drugs -- just to be sure?

  4. What would be the benefits if MS will be marked as a dementia?
    I assume it will be just another stigmata put onto MSers. I am fine with the ones that already exist! ;)


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