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.