Saturday, 2 March 2013

Poll results: cognitive relapses

#MSBlog: Cognitive relapses are part of the hidden burden of MS. Why don't we measure them?




"The results of this survey are clear; up to 50% of MSers are aware of having had, or possibly having had, a cognitive relapse. The problem is that unless the relapse affects part of the nervous system that is captured by the neurological examination, i.e. the EDSS, it cannot be considered a relapse. Hence we are probablt missing a large number of relapses. To objectively capture cognitive relapses we would need to extend the neurological examination to include cognition. This is difficult as most neuropsychological examinations take time to complete and need a specialist neuropsychologist to perform the assessment. Hopefully the Brief International Cognitive Assessment for MS or BICAMS (see below) will deal with this issue."

"Another issue this survey highlighted is the one of perceived cognitive slowing that occurs during a relapse. Only 27% of respondents said that they had not noticed this effect. Therefore the majority of MSers with relapses have cognitive slowing during a relapse. This is an issue that needs further investigation. I am not surprised by this observation; it is something I noticed years ago. Why does it occur? I am not sure but I think it is related to inflammation within the brain. As you know a relapse occurs due to focal inflammation at a particular site within the brain. The size and location of the lesion is responsible for the symptoms of the relapse. If the lesion is an eloquent area it causes symptoms, for example loss of vision, double vision, sensory loss, weakness, unsteadiness of gait, bowel, bladder or sexual dysfunction  etc. Most new lesions don't occur in eloquent areas and are therefore silent; for every relapse there are 10 or more lesions that come and go that you are not aware of; the so called hidden burden of MS. Are these lesions only silent because we don't look for their effects? For example, their impact on cognition. Cognitive relapses are the case in point. Back to my previous line of thought; inflammation produces many chemical mediators and other inflammatory signals that affect brain function; in particular the cytokines interleukin-1 and TNF-alpha. These cytokines are responsible for sickness behaviour (fatigue, somnolence, reduced appetite, reduced attention, fever) that occurs with systemic inflammation, for example when you have a viral infection. As  these cytokines are released as part of the inflammatory process they decrease the functioning of the brain and result in cognitive slowing. An analogy would be the way you feel cognitively when you have the flu. When I have the flu I have difficult doing cognitive tasks all I want to do is take and anti-inflammatory and lie down and sleep. Some MSers feel like this intermittently for no apparent reason; I am sure if we investigate them they would have evidence of active inflammation within the brain!"

Benedict et al. Brief International Cognitive Assessment for MS (BICAMS): international standards for validation. BMC Neurol. 2012 Jul 16;12(1):55.

An international expert consensus committee recently recommended a brief battery of tests for cognitive evaluation in MS. The Brief International Cognitive Assessment for MS (BICAMS) battery includes tests of mental processing speed and memory. Recognizing that resources for validation will vary internationally, the committee identified validation priorities, to facilitate international acceptance of BICAMS. Practical matters pertaining to implementation across different languages and countries were discussed. Five steps to achieve optimal psychometric validation were proposed. In Step 1, test stimuli should be standardized for the target culture or language under consideration. In Step 2, examiner instructions must be standardized and translated, including all information from manuals necessary for administration and interpretation. In Step 3, samples of at least 65 healthy persons should be studied for normalization, matched to patients on demographics such as age, gender and education. The objective of Step 4 is test-retest reliability, which can be investigated in a small sample of MS and/or healthy volunteers over 1-3 weeks. Finally, in Step 5, criterion validity should be established by comparing MS and healthy controls. At this time, preliminary studies are underway in a number of countries as we move forward with this international assessment tool for cognition in MS.


"We are involved in the BICAMS initiative and many MSers at our centre are participating in the study to evaluate it in the UK. Thank you for helping!"

8 comments:

  1. Prof G I've got a question which is a bit related since we are talking about lesions - what about grey matter lesions? I know they are not detectable but if they occur, do they cause symptoms akin to WM lesions or not? Also, do GM lesions mean automatically nerve loss or do they remyelinate themselves? Thanx.

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  2. Grey matter lesions are very important; they are probably the lesions that are responsible for cognitive impairment and are probably one of the causes of cognitive relapses.

    It has been shown that they remyelinate well; but are also associated with cell loss. This work has been done by Bruce Trapp and colleagues at the Cleveland Clinic.

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  3. What I remember of Bruce Trapp's work is that when axons are demyelinated, they have to work extra hard and that causes them to become hypoxic. If that is what's going on, there has to be some pharmaceutical that would help?

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    1. Yes, sodium channel blockers. This is why we are using phenytoin and oxcarbazepine in our two neuroprotectiion trials.

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  4. I dont have MS (as far as i know) but definitely go thru days or periods whe i'm much duller than usual, and assumed this is normal for everyone. For me these spells are usually during and around migraines.

    Couldnt 'cognitive relapses' be normal ups and downs?

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    1. Normal up and downs don't cause too many problems and fluctuate over hours. Cognitive relapses cause deficits that that take weeks to months to recover.

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    2. I had a severe relapse and lost many memories of what happened at the start of the relapse. The memories did come back but it took around ten months to get them back. They came back slowly and gradually, one memory triggering another memory. My relapse was so severe that I could not understand how to use a knife and fork for half a minute or so. I copied my mother using them anad it came back to me. It was like a mini stroke moment. I asked my MS nurse about the knife and fork thing and she said some MSers get cognitive problems like that. I've not had that before or again since.

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  5. I don't think any area in the brain is "idle" or "silent", we just don't have appropriate ways to examine the deficits. The neurology department at my hospital has no psychologist/neuropsychologist, nobody bothers with cognitive assessments.
    J

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