• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Multiple Sclerosis/Chronic Fatigue Syndrome overlap: When two common disorders collide

Bob

Senior Member
Messages
16,455
Location
England (south coast)
This came to my attention via Tom Kindlon on Twitter. Note that it's a 2014 paper. (Perhaps I shouldn't have placed this in the ME/CFS section of the forum, as it's a study of primary MS patients.)

It's not open-access.

[I'm not sure if they are testing these MS patients for ME symptoms or for chronic fatigue
. The abstract says that "the subjects were screened for CFS/ME symptoms", but it doesn't say which criteria were used.]

If these MS patients experience the same type of post-exertional exacerbation, as seen in ME patients, then this study could demonstrate an interesting association between MS and ME. Edit: However, Fukuda criteria were used in the study, and Fukuda doesn't require post-exertional exacerbation.


Multiple Sclerosis/Chronic Fatigue Syndrome overlap: When two common disorders collide
Gaber, Tarek A.-Z.K. | Oo, Wah Wah | Ringrose, Hollie
Journal: NeuroRehabilitation, vol. 35, no. 3, 2014
DOI: 10.3233/NRE-141146
http://content.iospress.com/articles/neurorehabilitation/nre1146

Abstract: INTRODUCTION: Fatigue is a major cause of disability and handicap in Multiple Sclerosis (MS) patients. The management of this common problem is often difficult. Chronic Fatigue Syndrome (CFS/ME) is another common cause of fatigue which is prevalent in the same population of middle aged females commonly affected by MS. AIM: This report aims at examining the potential coexistence of MS and CFS/ME in the same patients. METHOD: This is a retrospective study examining a cohort of MS patients referred for rehabilitation. The subjects were screened for CFS/ME symptoms. RESULTS: Sixty-four MS patients (43 females) were screened for CFS/ME. Nine patients (14%) with a mean age 52 (SD 9.7) who were all females fulfilled the Fukuda criteria for diagnosis of CFS/ME. Their symptoms, including muscular and joint pain, malaise and recurrent headaches, were not explained by the pattern of their MS. DISCUSSION: MS and CFS/ME are two common conditions with increased prevalence in middle aged females. As the diagnosis of CFS/ME is clinical with no positive clinical signs or investigations; it can be made with difficulty in the presence of another clear explanation for the disabling fatigue. Our results suggest that the two conditions may co-exist. Considering CFS/ME as a potential co-morbidity may lead to more focused and appropriate management.
 
Last edited:

anciendaze

Senior Member
Messages
1,841
I've read statements about something very much like PEM in a subset of MS patients in reports that go back before CFS was available as a diagnosis. I've also learned that patients treated by MS doctors don't always meet official diagnostic criteria for MS. One clinic reported about 20% in this category.

One problem with getting objective evidence of PEM in those patients is that most MS doctors recognize that having MS patients exercise to exhaustion is dangerous.

I've decided that there is no sharp distinction between relapsing/remitting MS and ME/CFS except by those who consider MS a real disease and ME a matter of false beliefs. There are patients with problems closely associated with MS, like optic neuritis, vertigo, ataxia or localized parathesias, which insurance does not want to touch, who never develop the full disease. There are also patients who do develop the full relapsing/remitting disease years after an initial episode. This has caused MS doctors to use the term Clinically Isolated Syndrome (CIS).
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
To my knowledge, and I do think we need a formal study, those with MS do not show the same problem on a 2 day CPET as ME patients do. PEM is one of those things that is interpreted different ways. This is a problem with every definition of ME and CFS ... either PEM is not required or its not sufficiently defined, together with appropriate doctor training. to be used properly.

Having said that I wonder if the whole notion of a disease category is even appropriate for diffuse neurological diseases. One thing that keeps kicking around at the back of my mind is that MS, ME and probably many other diseases are zones or regions in a multidimensional spectrum. We just attach labels to them and pretend they are discrete diseases. Even when we have biomarkers for ME, and we have candidates awaiting validation, this may still be the case.
 

Ecoclimber

Senior Member
Messages
1,011
Ah, thanks Dolphin. I scanned the abstract for the criteria used, but didn't notice it.

It's a shame they used Fukuda, because it doesn't answer the question of what sort of symptoms the subjects have. Fukuda patients can have PEM but they don't have to.

It's going to be hard to get past the ingrained mindset of reseachers from using a criteria other than Fukuda especially in correlation with other disease associations.for the immediate future.
 

SOC

Senior Member
Messages
7,849
While I consider it possible that MS and ME/CFS are variants of the same condition, I think it is also possible that there are other explanations for the similarities or overlaps, the most likely of which is misdiagnosis between similarly presenting, but different conditions, particularly when 'atypical' presentations are accepted.

Since this study used Fukuda, which does not require PEM, they did not necessarily find the coexistence of ME/CFS with MS. It is equally likely that they found a subset of MS with more than typical chronic fatigue (the symptom) and myalgia. It may be that an increase in the production of certain cytokines in both conditions is causing those symptoms in both groups.

Which isn't to say the conclusion of the study is definitely wrong. It's quite possible that MS and ME can coexist. I just don't think their study eliminated enough confounding factors to make their conclusion more likely than a number of other possible interpretations of their data.

I'd be very interested to see a study that compares immune function between MS and ME. And of course a 2-day CPET would be interesting as well. That would be more convincing in terms of coexistence or relatedness of the two conditions. Didn't Snell investigate MS with the 2-day CPET and find that MS patients do not have the failures that distinguish ME/CFS?
 

SOC

Senior Member
Messages
7,849
It's going to be hard to get past the ingrained mindset of reseachers from using a criteria other than Fukuda especially in correlation with other disease associations.for the immediate future.
It may not be as long as we might think at the moment if the IOM report is given any serious regard by government agencies. The report was very clear that PEM is the distinguishing feature of the illness. If that is accepted, Fukuda will have to be retired as not fit for purpose since it does not include the primary feature of the illness.

If, if, if....
 
Messages
15,786
I'd be very interested to see a study that compares immune function between MS and ME. And of course a 2-day CPET would be interesting as well. That would be more convincing in terms of coexistence or relatedness of the two conditions. Didn't Snell investigate MS with the 2-day CPET and find that MS patients do not have the failures that distinguish ME/CFS?
There were studies, which is discussed here somewhat: http://phoenixrising.me/archives/17902

A study by the Lights found that MS patients and healthy controls had their pain and fatigue return to normal 48 hours after exertion, while it was increased at that point for CFS patients. Discussed more in depth at http://forums.phoenixrising.me/inde...-after-exercise-in-cfs-ms-and-controls.13977/

And this one has Dr Snell (Workwell Foundation) discussing how MS and many other patients haven't shown our brand of exercise intolerance, including an experiment comparing a couple CFS patients with an MS patient and various other controls: http://forums.phoenixrising.me/inde...-on-exercise-and-cfs.24050/page-3#post-369210

I'd have to agree that anyone finding CFS in properly diagnosed MS patients is probably not using a good ME definition or is failing to assess PEM appropriately.
 

anciendaze

Senior Member
Messages
1,841
Please note that I said PEM was reported in a subset of MS patients. This was before anyone was doing the kind of testing done at Workwell. If we had better diagnostic criteria, and some clue about etiology, this might disappear. At present, we have to consider the possibility we are looking at either diagnostic confusion or a true spectrum of diseases.

On the subject of Fukuda vs. IOM, please note that IOM dropped primary depression as an exclusionary condition. In fact I'm not at all clear what would be an exclusionary condition for them.

In operational terms, apart from whatever nice words may appear elsewhere in the report, their flowchart for diagnosis merely requires substantial unexplained fatigue as an input to diagnosis. There is an exclusion for fatigue lasting less than six months. All other criteria (PEM, orthostatic intolerance, sleep disturbances, cognitive impairment) are subjective assessments by the doctor, and we already have numerous examples of precisely the kind of misinterpretation needed to place the patient in a psychosomatic wastebasket.

The diagnostic algorithm presented by IOM has not been implemented ("operationalized"). Depending on how this is done, HHS remains free to define the disease as a psychological problem which also includes primary major depressive disorders. They are also free to choose entirely different criteria based on new research. The IOM had no authority to set policy.

It looks like the purpose of the report was to buy time before anyone was forced to make a decision or take action, and deflect criticism to another body, which has since announced it is changing its name to National Academy of Medicine.
 

SOC

Senior Member
Messages
7,849
There were studies, which is discussed here somewhat: http://phoenixrising.me/archives/17902

A study by the Lights found that MS patients and healthy controls had their pain and fatigue return to normal 48 hours after exertion, while it was increased at that point for CFS patients. Discussed more in depth at http://forums.phoenixrising.me/inde...-after-exercise-in-cfs-ms-and-controls.13977/

And this one has Dr Snell (Workwell Foundation) discussing how MS and many other patients haven't shown our brand of exercise intolerance, including an experiment comparing a couple CFS patients with an MS patient and various other controls: http://forums.phoenixrising.me/inde...-on-exercise-and-cfs.24050/page-3#post-369210

I'd have to agree that anyone finding CFS in properly diagnosed MS patients is probably not using a good ME definition or is failing to assess PEM appropriately.
Thanks! That is sufficiently convincing for me to feel confident (given the currently available data) that ME and MS are not variations of the same illness. They may be related in some way, but definitely not the same. It would appear, therefore, that it is within the realm of possibility that some rare, extremely unfortunate individuals could have both conditions independent of each other. I'd say that number would be significantly less than is suggested by this paper... by orders of magnitude.
PEM is included in Fukuda, just not as a mandatory symptom.
Okay, I should have said it does not require PEM.

If PEM is the distinguishing feature of the illness, the one that identifies it uniquely from other illnesses and is a necessary requirement for the illness, any definition that does not include it as a mandatory symptom will unquestionably result in misdiagnoses. It's like making a broken bone an optional symptom for 'broken leg'. Allowing the distinguishing symptom to be optional is nonsense.

It may have made sense at the time, when we had a lot less data about ME/CFS, not to make PEM a mandatory symptom. However, knowing what we know now, Fukuda is outdated and not fit for purpose. Definitions, especially vague ones for poorly-understood conditions, have to be discarded as better data becomes available.

On the subject of Fukuda vs. IOM, please note that IOM dropped primary depression as an exclusionary condition. In fact I'm not at all clear what would be an exclusionary condition for them.
This makes perfect sense. There is no reason to think ME/CFS and MDD are mutually exclusive any more than MS or cancer and MDD are mutually exclusive. It's quite possible to have both conditions independent of each other. It would be both unfair and unscientific to exclude someone from an ME/CFS diagnosis simply because they have MDD. "I'm sorry sir, we can't diagnose and treat your cancer because you have MDD and the two are unrelated."

Exclusionary conditions are useful for the relatively rare situations of mutually exclusive conditions where an either/or diagnosis is needed. Diseases are best defined by what they are, not what they are not. This is why good definitions rarely include exclusionary conditions, and why the IOM committee did not include exclusionary conditions.

That said, it is critical that doctors understand that ME/CFS and MDD are not equivalent conditions any more than cancer and MDD are equivalent conditions even though some people have both.
The diagnostic algorithm presented by IOM has not been implemented ("operationalized"). Depending on how this is done, HHS remains free to define the disease as a psychological problem which also includes primary major depressive disorders. They are also free to choose entirely different criteria based on new research. The IOM had no authority to set policy.
Absolutely. There was no policy established by the IOM (it doesn't have that authority) and the SEID definition has no authoritative basis. HHS still needs to decide if it agrees that SEID describes the illness we have. Assuming it does, HHS still needs to find a way to operationalize the definition in a way that GPs can properly diagnose the condition described as SEID. That has not happened yet. It may never happen. We still have a lot of work to do before we have a functional definition of our illness.
 

jimells

Senior Member
Messages
2,009
Location
northern Maine
It may have made sense at the time, when we had a lot less data about ME/CFS, not to make PEM a mandatory symptom. However, knowing what we know now, Fukuda is outdated and not fit for purpose.

It made sense at the time because the intent was to re-define the illness out of existence. This is well documented, in the words of Dr Straus himself, a leading proponent of Fukuda.
 

Dolphin

Senior Member
Messages
17,567
Description from the paper of the 9 patients said to have MS and "CFS/ME"
The 9 subjects were all females with a mean age of 52 years (S D 9.7). Table 2 details the duration of MS, certainty of the diagnosis (confirmation by MRI imaging and/or lumbar puncture), main characters of MS and the level of mobility on presentation.

All patients had significant fatigue which fluctuated significantly in severity. The fatigue was strongly associated with post exertional malaise (patients feeling malaise or flu like symptoms after activities). All patients suffered from non-specific pain which was diffuse and did not follow any neuroanatomical distribution. The pain was strongly related to the level of fatigue. Seven subjects described a headache which was non-specific and also strongly associated with the fatigue. All subjects suffered from poor non refreshing sleep which was not associated with any MS related explanation such as nocturia or night spasms.

Four subjects described dramatic fluctuation in the level of mobility with days when they are bed bound and other days when they can walk outdoors independently with no aids. MS relapses were suggested for these patients and three of them received steroids for some of these attacks. Only three patients described recurrent sore throats or lymphadenopathy and eight described significant memory and concentration problems


Table 2

Summary of age, MS duration, level of mobility and main clinical features of the 9 subjects presenting with symptoms suggestive of CFS/ME

Age Duration of MS Diagnosis Level of mobility Clinical characteristics

Case 1 70 32 years uncertain Walks independently Sensory symptoms/somatisation
Case 2 47 11 years confirmed Walks independently Spastic paraparesis
Case 3 50 2 years confirmed Walks independently Sensory/neuropathic pain
Case 4 40 8 years confirmed Walks independently Sensory/cerebellar
Case 5 52 18 years confirmed Walks independently Sensory/balance/cerebellar
Case 6 64 10 years confirmed Walks independently Sensory/spasticity
Case 7 49 13 years confirmed Walks independently Spastic paraparesis
Case 8 59 11 years confirmed Wheelchair dependent Spastic paraparesis
Case 9 44 16 years confirmed Walks independently Sensory
 

Dolphin

Senior Member
Messages
17,567
However, we would like to give a short account to the management of one patient who had input from a specialised CFS/ME therapist.

3.1. Patient 5

This female had an 18 year history of MS. She described two types of relapses; one she called big relapse when she had significant deterioration of her neurological impairments. This type of relapse happened every few years and warranted the use of immunomodulator medications. The last big relapse happened five years ago.

The patient described another type of what she described as small relapses. These happened every 2-3 weeks with severe fatigue, pain, malaise and headaches. These usually followed excessive activities. The patient had a perfectionist personality and a clear boom and bust behaviour.

The patient was asked to complete an activities diary and the therapy input aimed at recognising the pattern of activities and the potential energy expenditure of each activity. Cognitive Behavioural Therapy (CBT) focused on challenging the patient’s perception of how important some of her activities are and encouraged more relaxed approach to achieve prompt approach to her tasks. Behaviours leading to energy waste that could be compensated for by other methods were identified and behavioural changes encouraged. Other harmful coping mechanisms such as reliance on stimulants (e.g. caffeine) was also challenged.

The patient achieved significant improvement in her fatigue levels and she admitted at the end of the programme that she can clearly identify the nature of her symptoms and differentiate between MS and CFS/ME related symptoms.
Note that the underlined bit is not like the CBT that has been tested in trials in the UK and the Netherlands (which is said to be "evidence based" (by others).

Another example showing their view of therapy for "CFS/ME" is different to the mainstream, so-called evidence-based approach is here:
A successful CFS/ME rehabilitation programme may lead to reduction in the over-all activities performed by the patient but its main value is the reduction of the unpleasant symptoms of fatigue, pain, headaches, sleep problems etc on one hand and also the breakdown of the vicious cycle of fluctuations between good and bad days (Burns, 2012).

"Graded activities" which probably means graded activity does get mentioned in the final sentence but who knows why it is there (maybe following a suggestion from a reviewer?).
These patients are at increased risk of not only being mismanaged with inappropriate pharmacological agents but also may miss out on specialised interventions for fatigue within a psychosocial context such as CBT and graded activities.
 
Last edited:

Dolphin

Senior Member
Messages
17,567
Here's what they say on post-exertional malaise

We disagree with Morris and Maes’ suggestion that fatigue pattern in MS is similar to CFS/ME symptoms (2013). The authors failed to cite any source to support their claim that MS associated fatigue is associated with post exertional malaise and/or non-specific pain. We were also unable to locate any publication making that claim. Until a strong link between MS and CFS/ME is established indicating a pathological link, we feel that co-existence of 2 common conditions in vulnerable patients’ population is the most reasonable explanation for our clinical observations
 

Dolphin

Senior Member
Messages
17,567
They're a bit obsessed it seems to me in seeing "CFS/ME" as being perfectionists. The other thing they keep bringing up is boom and bust.

All patients [with CFS/ME and MS] admitted having perfectionist driven personalities and reported boom and bust behaviour (doing too much in a good day despite recognising that they will probably suffer from unpleasant symptoms in the few days afterwards).

(on patient 5. full extract above)
The patient had a perfectionist personality and a clear boom and bust behaviour.

They [all patients with CFS/ME and MS] have also demonstrated clear boom and bust behaviour which, in conjunction with their perfectionist personalities are strongly associated with CFS/ME patients (VanNess, 2010).

Despite the fact that generic fatigue management rehabilitation programmes routinely offered to MS patients encompass most of the management strategies used for CFS/ME patients (Heesen, 2012), CFS/ME management plans focus on addressing the perpetuating factors for the fatigue such as a perfectionist personality or boom and bust behaviour (Smith, 2012).


We would like to propose the following characters as red flags that should raise the suspicion that the MS might be associated with a CFS/ME:

[..]

4. Perfectionist personality exhibiting a boom and bust behaviour.

If you a condition like ME/CFS which can cause considerable post-exertional malaise, a lot of patients are going to have periods when they are doing less well/suffer post-exertional malaise which could be called "bust". It doesn't necessarily mean the patients were "booming" (indeed there were one or more studies which found that patients with CFS had no more variation in their day-to-day activity levels than healthy controls).
 
Last edited:

Dolphin

Senior Member
Messages
17,567
There overall motivation seems to be they think some MS patients could benefit from "CFS/ME" management programs rather than simply pharmacological approaches.

It would be interesting to know more about their views on "CFS/ME". As mentioned above, they don't appear to fit into the normal rehab group who are very focused on graded activity and exercise.
 

Dolphin

Senior Member
Messages
17,567
(Junk Junk)
One of the authors is called Wah Wah Oo! Think it would take me some time to get used to that name.
 

Dr.Patient

There is no kinship like the one we share!
Messages
505
Location
USA
@Dolphin Unable to post under there, but this is reply to post #15


These are the most useful descriptions of CBT and GET that apply to us mecfs patients!!! The REAL value of CBT is, like said above, identifying your behaviors that increase your symptoms and reducing them. Also, helping you cope with this disabling, chronic illness.

And the REAL value of GET/rehab is that even though it reduces overall activities, the relief from horrible symptoms like fatigue, crashes, etc improves quality of life.

It is a graded exercise therapy all right, but it's graded down, not up. Any sensible doctor can see that patients' symptoms and functionality worsen when grading up- this paper will help them see that grading down is an option as well.

If physicians who recommend CBT/GET are shown this paper, they probably will be more willing to help patients the right way, and not the wrong way.

Do you have a link to the full paper, thanks.