Do you relate to this list of facts in relation to MS-fatigue?
- The most common spontaneously reported symptom for pwMS is fatigue.
- PwMS use the words “tired,” “exhausted,” “wiped out,” and having “little or no energy” to describe their fatigue.
- More patients rated fatigue as their “most troubling symptom” compared with other MS-related symptoms.
- Half of the people living with MS report feeling constantly fatigued and more than 90% reported experiencing fatigue at least daily.
- The top three most frequently reported negative impacts of fatigue were social functioning, emotional well-being, and cognitive functioning.
- PwMS describe themselves as “homebodies,” as fatigue limited their social interactions with friends and family and impacted the types of activities they could participate in.
- PwMS attribute their inability to think clearly or focus for long periods of time to their fatigue.
- PwMS report experiencing depression and anxiety because of their fatigue, which would often have further negative effects on their relationships with friends and family.
Although this list comes from a new qualitative study on MS-related fatigue (see below) they are not new insights.
As fatigue is a reasonably well-defined problem in MS we should be asking ourselves why haven’t we cracked it and have effective treatments to manage it?
I think we can crack-it but we have to acknowledge that MS fatigue relates to (1) active inflammation and (2) the consequences of the damage that inflammation causes. If we acknowledge this then we are half-way towards treating and preventing MS-related fatigue, i.e. treating MS early (before too much damage occurs) and effectively (NEDA and beyond).
The following is what we know about MS-related fatigue.
Inflammation in the brain causes fatigue. This is due to inflammatory mediators or cytokines, in particular, interleukin-1 (IL-1) and TNF-alpha, which trigger sickness behaviour. Sickness behaviour is the behavioural response we have to inflammation, which forces us to rest and sleep so that our body can recover. This is what happens to you when you get a viral infection; in fact many of the pwMS I look after describe their fatigue as being similar to the fatigue they experience when they get flu. Sickness behaviour from an evolutionary perspective is well conserved and occurs in most animals. This type of fatigue needs to be managed by switching off ongoing inflammation in the brain. This is why so many pwMS who go onto highly-effective DMTs come back saying ‘I feel so much better, my fatigue and/or brain fog has cleared’. Do you relate to this? This is why recent-onset fatigue that can’t be explained by other factors (see below) may indicate MS disease activity. At present fatigue on its own does not constitute a relapse, but there are some of us who would disagree; particularly if we investigate more deeply we often find subclinical/MRI or biomarker (neurofilament) evidence of relapse in these patients.
Another cause of fatigue is the exercise-related conduction block. This is when pwMS notice their legs getting weaker with exercise. We think this is due to demyelinated, or remyelinated axons, failing to conduct electrical impulses when they become exhausted. Exercise-induced fatigue is probably the same as temperature-related fatigue; a rise in body temperature also causes vulnerable axons to block and stop conducting. To deal with this type of fatigue we need therapies to promote remyelination and to increase conduction. These types of fatigue are treated by rest, cooling and possibly drugs such as fampridine that improve conduction. At the heart of this type of fatigue is localised energy failure.
The other cause of fatigue is neural plasticity. When the brain is damaged by MS other areas are co-opted to help take over, or supplement, the function of the damaged area. In other words, it takes more brainpower to complete the same task that normal people do. This type of fatigue usually manifests as mental fatigue and is why pwMS have difficulty concentrating for prolonged periods of time. At present we have no specific treatment for this type of fatigue except to prevent it by treating MS early and effectively. Some patients find amantadine and modafinil helpful. In short, preventing the loss of brainpower, or damage, in the first place should prevent this type of fatigue.
Fatigue can also be related to so-called co-morbidities, or other diseases, that are related to MS. The big co-morbidities that cause fatigue, which need to be screened for are:
- Infection – we all get tired when we have infections; it triggers sickness behaviour
- An underactive thyroid gland or hypothyroidism – hypothyroidism is commoner in pwMS
- Poor sleep hygiene and/or sleep disorders – if you are not sleeping well you feel tired in the morning
- Obesity – when you are overweight it takes more energy to perform physical tasks
- Depression and anxiety; fatigue is a common symptom of depression and anxiety and unless this is screened for and treated in persists.
- Side effects of drugs; in particular drugs that cause sedation and from DMTs. Anticholinergics and anti-spasticity drugs are sedating and blunt cognition and may worsen MS-related fatigue. Specific side effects, for example, the flu-like side effects from interferon-beta may make fatigue worse.
- Excessive alcohol consumption; although classified as drug alcohol causes and exacerbates MS-related fatigue in several ways, most notably by causing poor sleep hygiene and exacerbating depression.
- Deconditioning; deconditioning is simply the term we use for being unfit. If you are unfit, performing a demanding physical task makes you tired. Deconditioning is treated with exercise, which paradoxically can reduce fatigue.
- Poor nutrition; some pwMS are anorexic and eat very poorly and hence have little energy as a result of this. Although this is quite rare I look after a few pwMS with this problem. Similarly, overnutrition may have the same effect. Some of the hormones your gut produce cause you to feel tired and want to sleep; i.e. the so-called siesta effect. Reducing the size of your meals and changing your eating behaviour may improve post-prandial (after eating fatigue). I have a few patients who avoid eating lunch for this reason. Too much fast-sugar (high-glycaemic index) raises insulin levels that cause post-prandial insomnia or food coma. Going onto a low carbohydrate diet helps this type of fatigue.
It is apparent from this discussion that fatigue in MS is more complex than you realise and needs a systematic approach to be treated and managed correctly. So be careful, or at least wary, when your neurologist simply wants to reach for the prescription pad to get you out of the consultation room as quickly as possible. Like other MS-related problems, an holistic and systematic approach is needed to manage and treat MS-related fatigue correctly.
On a positive note, you should also be able to use the information in this post to help formulate a fatigue self-management plan and prepare yourself to ask the really challenging questions when you next see your MS team.
I would be interested to know if any of you have any stories to relate with us about your attempts to self-manage your fatigue, particularly during lock-down.
Penner et al. Exploring the Impact of Fatigue in Progressive Multiple Sclerosis: A Mixed-Methods Analysis. Mult Scler Relat Disord 2020 May 27;43:102207.
Background: Patient-focused literature on fatigue in progressive forms of multiple sclerosis (MS) is sparse. This study aimed to explore progressive MS patients’ experiences of fatigue.
Methods: Adult patients in the United States with primary progressive MS (n=21) and secondary progressive MS (n=23), recruited from research panels, completed the following PRO measures: Patient Global Impression of Severity (Fatigue) (PGI-F); Fatigue Scale of Motor and Cognitive Functions (FSMC); Modified Fatigue Impact Scale (MFIS); Patient Health Questionnaire, two-item version (PHQ-2); and Patient Determined Disease Steps (PDDS). Patients subsequently participated in a 45-minute semistructured telephone interview and were asked to describe their MS symptoms and to comment on how MS affected their day-to-day lives. More detailed questions followed on the nature of their fatigue, including symptoms, impacts, frequency, and bothersomeness.
Results: Patients’ mean age was 52.5 years, mean time since diagnosis was 14.7 years, and 81.8% were female. 79.5% of patients were unemployed and/or receiving disability benefits. Of all spontaneously reported MS symptoms, fatigue was the most common (n=38, 86.4%), followed by ambulation problems (n=31, 70.5%) and muscle weakness (n=25, 56.8%). Patients used the words “tired,” “exhausted,” “wiped out,” and having “little or no energy” to describe their fatigue. More patients rated fatigue as their “most troubling symptom” (n=17, 38.6%) compared with other MS-related symptoms. Half of patients reported feeling constantly fatigued, and more than 90% reported experiencing fatigue at least daily. The top three most frequently reported negative impacts of fatigue were social functioning, emotional well-being, and cognitive functioning (all >80%). Patients described themselves as “homebodies,” as fatigue limited their social interactions with friends and family and impacted the types of activities they could participate in. Patients attributed their inability to think clearly or focus for long periods of time to their fatigue. Patients also reported experiencing depression and anxiety because of their fatigue, which would often have further negative effects on their relationships with friends and family. On the fatigue PRO measures, mean (standard deviation) scores were 75.2 (14.7) on the FSMC and 55.0 (15.2) on the MFIS. Most participants scored in the “high” fatigue category on the FSMC (84.1%) and above the clinically significant fatigue threshold (86.4%). MFIS and FSMC total scores correlated with PGI-F (polyserial correlations r=0.74 and r=0.62, both p<0.01) and PHQ-2 (r=0.56 and r=0.57, both p<0.01), but not with PDDS (r=0.09 and r=0.02, both p>0.05).
Conclusions: Fatigue is a common, troublesome, and disabling symptom which has a profound impact on patients’ daily lives, as evidenced by qualitative analyses and high scores on established fatigue measures observed in this sample. These findings provide insights into the burden of fatigue and can inform its measurement in both clinical and research settings. Treatments that improve the symptoms of fatigue or prevent exacerbations are needed for patients with progressive MS.
CoI: multiple
“As fatigue is a reasonably well-defined problem in MS we should be asking ourselves why haven’t we cracked it and have effective treatments to manage it?… I think we can crack-it but we have to acknowledge that MS fatigue relates to (1) active inflammation and (2) the consequences of the damage that inflammation causes.“
It’s not rocket science. Address the real MS and everything else should fall into place – disability worsening will stop; fatigue will fall away; socialising will be resurrected; relationships will be saved; jobs will be retained… we talk and talk and talk and test hypotheses…. Can’t we just get on with it and solve this riddle of a disease and give people their lives back?
Re: “Address the real MS and everything else should fall into place..”
Yes, I agree. This is why we are working on smouldering MS and the viral aetiology of MS.
I find – post facto – that when I am knackered it is often because I have not drunk enough water during the day. Coffee is a poor substitute but lovely to drink on top of being properly hydrated. I ‘try’ to keep a water bottle to hand as it is amazingly easy to overlook until it is too late.
I also take Modafinil 200mg (prescribed by a forward thinking neuro) once a day with breakfast as the main effect this has on me is a restoration to closer to normal of cognitive ability. There has never been a sensation of amphetamine-like stimulation. Just the ability to focus on complex mental tasks – such as writing a dissertation, reading complex documents etc – for a good 3-6 hours when, if it was possible at all, it was fleeting.
I get the feeling that many neurologists view any type of pharmacological neurostimulator (if that is the correct term) with a sort of puritanical distaste, as if prescribing that is one step from allowing the creation of some drug-crazed individual. It takes me closer to, but not fully at a more normal cognitive state. It doesn’t give advantage over mortals by getting me all sped-up and wired.
Many pwMS that I talk to where the topic crops up – and I mention my Modafinil – come back with the info that their neurologist doesn’t sanction/approve of such interventions. This staggers m,e. If the neuro had the remotest idea what it was like to have constant fatigue – not the stay up late revising tiredness – I think they may be more sympathetic.
Re: “I get the feeling that many neurologists view any type of pharmacological neurostimulator (if that is the correct term) with a sort of puritanical distaste..”
That is because modafinil is not licensed to treat MS-related fatigue. Neurologists are risk-averse and are not keen to take on unnecessary risks.
The NHS does not necessarily cover you medicolegally for off-label prescribing. Nor do they cover you for private prescriptions.
I have never heard this described but your description of neurologists being risk-adverse is so right on!!! How is a response “it doesn’t follow Health Canada Guidelines”!!! An example is fampyra being discontinued because walking speed did not increase.
The only real symptom (other than a mild off-balance feeling) that I had when I was finally diagnosed was absolute fatigue with cog fog that didn’t go away no matter how much I slept or lay about doing nothing. The way I described it was feeling like I was either getting or just getting better from the flu. Fortunately, after about 3 moths of symptoms, 6 months of various specialists my GP sent me to a neuro… and the rest is history, although even he didn’t really expect to see anything in the MRI.
Just finished second year of cladribine, fatigue, cog fog and balance are better, but not back to what they were, I keep hoping that I will wake up one morning feeling 100% but I don’t think it is going to happen.
Re: “Just finished second year of cladribine, fatigue, cog fog and balance are better, but not back to what they were, ….”
I find with the IRTs (cladribine and alemtuzumab) it takes longer for the fatigue and cog-fog to improve, which is unlike natalizumab where the improvements are more rapid.
I suspect the improvements are due to anti-inflammatory effects.
Hooray… so there is still a chance then!😀
I have to say that unlike KC below, I never had a short period after year 1 Mavenclad where I felt like the energiser bunny, just a gradual improvement over a few months but not to the bunny stage. But starting to feel a little bit more improvement after year 2, hoping it isn’t my imagination, and hoping it will continue.
Fatigue has been a major player for me. Sleep studies should be mandatory for all those with ms, as well as FULL thyroid panels.
However what I would like to note – for nine weeks after year 1 Mavenclad I was a new person. Missing – the cognitive fatigue completely as well as general. Still some conduction block on weak side as usual but I operated at a level I hadn’t for years. Completely clear headed. Energizer bunny. It was like a switch was turned on. Thinking all day and way better executive function.
Sadly that has passed. But my question – why? There seems to be a small proportion of people in the Mavenclad group that are experiencing this.
I know when I am fighting something it sucks the life out of me so my guess is I stopped fighting latent virus. History here but already on an antiviral (poor) for one. Bit concerned that CoVid19 can become latent.
I crashed when my monocytes and lymphocytes were back to normal range and am now back to my MS “normal” …
I would love some good scientific hypothesis about why this could happen. I obviously hate the thought that I will have to wait for 10 months for another two months feeling vibrant. I’m intrigued about the possibility of a monocytes connection/association since it’s only a small group experiencing this. My lymphocytes were halved but monocytes down by 80%.
I realize you don’t speak to individual cases; I’m more concerned about the hypothetical what possibilities could have been responsible for the nine weeks of absolute clarity. For nine weeks, you did crack the mystery of my particular fatigue.
As a 52 year old woman & 9 years post diagnosis & 2 rounds of alemtuzumab, where do I start overcoming fatigue?
My friends around the same age as me tell me that they’re experiencing similar problems with fatigue & mental blocks, but then I see them going to the gym after a day’s work etc. My day stops once my evening meal has finished, simply no more energy left. I also feel that I am missing chunks of my life as I have to sit & rest throughout the day.
Reading menopause articles I wonder if this could be it, although no other menopause symptoms & could HRT be the solution – or am I slowing due to MS?
On a positive note, I have taken this lockdown time away from work to exercise regularly, eat healthier & am losing that extra weight that has crept up on me as I was using sugary snacks as a quick fix to bolster energy levels – stupid, I know, but was stuck in that cycle!
It was interesting to read Dominc’s experience with Modafinil. So where’s the best place to start & why – GP or neuro?
Re: “…why? There seems to be a small proportion of people in the Mavenclad group that are experiencing this.”
The recurrence of fatigue may be due to inflammation returning and the consequent sickness behaviour.
When I got some MS symptoms for the first time, and the MRI showed some lesions, some things fell into place.
Maybe the MS was responsible for my lifelong underachievementa, laziness/lack of energy, and constant state of mental muddle
MS has a long presymptomatic and/or prodromal phase that can be many years and potentially decades.
I’m 38, MS for 9 years, have only been on a DMT (ocrelizumab) since last summer as ‘only’ had my diagnosing relapse 9 years ago, and then my second one led to treatment last year.
I somehow feel like a bit of a fraud as my EDSS is 0 and I don’t suffer at all with fatigue.
Is this basically something I have to be ready for in the future…
No, not necessarily if you remain NEDA and have not sustained much damage before starting your DMT.
20 months since diagnosed with SPMS, RRMS not picked up, disguised by other health issues, Not the retirement I had planned. Very sensitive to Modafinil, mood swings, anger etc. Stopped taking it.
I have to pace my self mentally & physically. Don’t do much in the mornings, catch up with emails etc. My sweet spot when I can things done is from 2.00pm through to 5.00pm. Unless it is hot, then that wipes out the day. However by 7.00pm my fatigue has ramped up, and I don’t really do much until bedtime.
My energy level is perhaps 10% compared to 6 years ago.
This is what I call the battery approach to fatigue management. You treat your energy levels like a charged or semi-charged battery and you only have so many hours in a day before they run dry. The question is can you increase the size and power of the battery? I think some of the strategies mentioned in the post address this.
Do you want your energy store to be an Amazon basic battery or a Duracell battery or even a rechargeable Energizer battery?
Interesting article …
1) my personal view of fatigue in MS is that is should have another name. Yes the closest thing we can use to describe it is fatigue, but this misrepresents what is actually going on for we PwMS. Fatigue is not a strong enough name for the symptoms. Nor is lassitude. Is it inflammatory exhaustion??
2) I’ve recently surfaced from an 18m doldrums episode – relapse? (I’m fighting off acknowledging the SPMS classification atm so I’m unsure about typical length of progression ‘dips’) … since emerging I have started 10-15 minute cold showers, time-restricted eating and concentrated healthy eating … still slightly obese but ?fatigue?? has reduced. Taking control where we can with healthy intention can make a difference.
Duracell battery, more energy in the day would be great
Fatigue is the number one symptom in
Lupus
crohn’s disease
systemic sclerosis
Rheumatoid Arthritis
Etc
https://en.wikipedia.org/wiki/Autoimmune_disease
I’ve definitely struggled with fatigue at times. Personally I have 2 types of fatigue. One when I’m having a relapse and nothing helps. In this case I feel like my limbs are made out of cement. I then have a more chronic type of fatigue that I’ve been highly successful in managing. Number one in addressing it is exercise (thankfully I do not suffer exercise induced fatigue). If I fail to get some vigorous exercise for more than 2 days in a row the clouds roll in physically and cognitively. As counter intuitive as it is exercise helps a great deal. In addition, after a relapse, I’ve done guided energizing meditation. The online stuff says its hypnosis but for me its not that. I take 20 min, listen to one, and its a combo nap / visualization. Sounds silly but I decided that my brain was lying to me about my fatigue and I need a way to reset it back to something close to ‘normal’. Not sure if the impact has been real or imagined regardless it has helped get me functioning again.
Nice
🙂
I’ve suffered from MS for 45 years but fatigue is the new kid on the block, started just over 10 years ago and it is now a major irritant. Definitely cope better in the morning, after supper I’m a complete wreck. Must now always watch what physical activities I do and that includes just standing up on my feet.
I can endure double vision, drop foot and drop leg, these are consistently awful but at least they are a known problem where as fatigue comes and goes. Some days are good, some days are dreadful. The only reliable problem is that fatigue/exhaustion only occurs when it is too late to do anything about it except to find a place to get the weight off my feet.