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Cause of Fatigue in MS (and ME/CFS)


Phoenix Rising Founder
Multiple Sclerosis is an intriguing disorder for us because a subset of MS patients have very severe fatigue and they don't know why. They do know that the fatigue is not caused by the demyelination that is present in MS. They know that because the people who have high rates of fatigue don't necessarily have high rates of demyelination. So why are these particular patients so fatigued? This study might provide some of the answers.

1: Eur J Neurol. 2009 Oct 1. [Epub ahead of print] Links
Fatigue and processing speed are related in multiple sclerosis.Andreasen AK, Spliid PE, Andersen H, Jakobsen J. Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.

Background: Fatigue is common in multiple sclerosis (MS) and could be related to impaired processing speed caused by MS specific brain alterations. The objective of this study was to examine the relationship between processing speed and fatigue in patients with relapsing remitting MS.

Methods: Patients with EDSS score </=3.5 were grouped as fatigued [Fatigue Severity Scale (FSS) score >/=5.0] or non-fatigued (FSS score </=4.0). Patients with FSS scores >/=5 were categorized as primary or secondary fatigued according to various indices. A cognitive test battery obtained from Wechsler's Adult Intelligence Scale-III/Wechsler's Memory Scale-III was applied.

Results: Processing speed (Digit Symbol Coding) was lower amongst all MS patients being 9.4(2.9) in primary fatigued, 8.3(2.8) in secondary fatigued and 10.3(2.7) in non-fatigued versus 12.3(3.0) in healthy controls. In the combined group of primary and secondary fatigued MS patients, processing speed was slower than that in non-fatigued MS patients and inversely related to fatigue (r = -0.35; P < 0.05). No such relationship could be established in non-fatigued MS patients or in healthy controls.

Conclusion: The degree of fatigue in MS is related to processing speed impairment and longitudinal studies should clarify their mutual dependency.

It seems like the fatigued patients had trouble processing or taking in information. They simply weren't able to take in information from the outside environment as effectively as non fatigued MS patients or the healthy controls. Some researchers do believe that ME/CFS is an information processing disorder. They believe that too much information is getting through - that the gates that are supposed to filter information to the brain - are open too wide. I wonder if that has application here


Many MS patients have undiagnosed lyme or other bacterial infections. Some get well on the C.A.P. protocol or lyme protocols.


Senior Member
Looks like different parts of the brain are used by MS patients when processing information compared to healthy controls. Whether this difference is linked to fatigue as well is another matter.

1: J Int Neuropsychol Soc. 2009 May;15(3):383-93. Links

Examination of processing speed deficits in multiple sclerosis using functional magnetic resonance imaging.Genova HM, Hillary FG, Wylie G, Rypma B, Deluca J.
Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA. hgenova@kmrrec.org

Although it is known that processing speed deficits are one of the primary cognitive impairments in multiple sclerosis (MS), the underlying neural mechanisms responsible for impaired processing speed remain undetermined.

Using BOLD functional magnetic resonance imaging, the current study compared the brain activity of 16 individuals with MS to 17 healthy controls (HCs) during performance of a processing speed task, a modified version of the Symbol Digit Modalities Task. Although there were no differences in performance accuracy, the MS group was significantly slower than HCs.

Although both groups showed similar activation involving the precentral gyrus and occipital cortex,the MS showed significantly less cerebral activity than HCs in bilateral frontal and parietal regions, similar to what has been reported in aging samples during speeded tasks. In the HC group, processing speed was mediated by frontal and parietal regions, as well as the cerebellum and thalamus. In the MS group, processing speed was mediated by insula, thalamus and anterior cingulate.

It therefore appears that neural networks involved in processing speed differ between MS and HCs,and our findings are similar to what has been reported in aging, where damage to both white and gray matter is linked to processing speed impairments.

PMID: 19402924 [PubMed - indexed for MEDLINE]


Senior Member
I'm intrigued by the timing of awareness regarding fatigue in MS which seems to coincide with a couple of developments.

MS is now sometimes diagnosed based on MRI findings alone or in concert with less than conclusive EVP and LP findings.

Those of us with ME may have hyperintensities on brain MRI which are non-specific but can be in areas involved in MS. (I had more than a dozen T2 weighted hyperintensities in the peri-ventricular regions, implicated in MS, many years ago.) Our lesions tend to be small and punctuate while MS lesions are larger but not all neurologists are strict about the diagnostic process.

The awareness of, and interest in, MS fatigue has really increased in the last two decades as the number of ME/CFS cases has risen.

I am quite sure there are people diagnosed with MS who actually have ME and visa-versa. I carry a diagnosis of "possible MS", based on my MRI, and was once told by a doc. that I had MS. But, the course of my illness has been classic ME. Or, so I thought until I began reading about supposed cases of MS following a viral illness... hmmmm?!

Very little is known about MS - Multiple Sclerosis means, simply, multiple scars - an observation not wholly dissimilar to, nor more revealing than: chronic fatigue. It is very easy to mix them up (ME and RRMS with fatigue) in a clinical setting.



Phoenix Rising Founder
I too was assessed for MS and the findings were kind of similar to yours; they found abnormalities but they didn't fit the MS prototype. Luckily I didn't have MS.

I'm struck by the fact that if you have difficulty processing information then it takes a lot more energy to do it correctly; this suggests that ME/CFS patients have to work harder to do the same mental tasks. Research has shown that they have difficulty blocking out background noises; this is more the same - they have to expend energy doing things that healthy people take for granted. We don't even realize this is happening.

I really wonder about movement in this regard; these is some evidence that suggests that the areas of the brain that plan movement are impaired in ME/CFS. That would make it much more effortful for us to simply move. There is also research that suggests that we are not activating as many muscle fibers during movement.

This is all such interesting stuff; these are all positive studies - but most of them have been dead ends in that even though they were successful there's been very little follow-up. I just don't know why this is - it kind of blows my mind. These studies were successful!

Here's a link to some more info on the intersection between MS and CFS and fatigue.