“Fatigue is one of the most disabling symptoms MSers suffer from and in over 50% of MSers it is the one symptom they would like to get rid of most. MS-related fatigue is complex and has several underlying mechanisms. Firstly, inflammation in the brain causes fatigue. This is due to inflammatory mediators (IL-1 and TNF-alpha) triggering sickness behaviour. The latter is a behavioral response we have to inflammation, which forces us to rest and sleep, so that the body can recover. This is what happens to you when you get a viral infection; in fact many of the MSers 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 MSers who go onto highly-effective DMTs comeback saying ‘I feel so much better, my fatigue and/or brain fog has cleared’.”
“Another cause of fatigue is exercise related conduction block. This is when MSers 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. These types of fatigue are treated by rest, cooling and possibly drugs such as fampridine that improve conduction.”
“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 brain power to complete the same task that normal people do. This type of fatigue usually manifests as mental fatigue and is why MSers have difficulty concentrating for prolonged periods of time. At present we have no specific treatment for this type of fatigue.”
- Infection; we all get tired when we have infections; it triggers sickness behaviour
- An underactive thyroid gland or hypothyroidism; this is commoner in MSers
- Poor sleep hygiene and/or sleep disorders; if you are not sleeping well you feel tired in the morning
- Obesity; being overweight takes more energy to perform physical tasks
- Depression and anxiety; fatigue is a common symptom of depression
- Side effects of drugs; in particular drugs that cause sedation and from DMTs (e.g. as part of the flu-like side effects from interferon-beta)
- 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 reduces fatigue
- Poor nutrition; some MSers 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 MSers with this problem.
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 of the consultation room. Like other MS-related problems a holistic approach is needed to manage and treat MS-related fatigue correctly.”
“If you have time it would be helpful if you could complete the survey below. The survey will allow us to take this discussion forward over the next few weeks. Engaging with this issue should help you self-manage your fatigue.”
OBJECTIVE: Fatigue affects more than 60% of MSers and is one of the most troublesome symptoms of the disease. Current treatment options for MS fatigue include amantadine, modafinil and acetyl-l-carnitine (ALCAR). The aim of our study was to compare efficacy of amantadine, modafinil and ALCAR with placebo in MSers.
METHODS: MSers with a disability level ≤5.5 on the Kurtzke Expanded Disability Status Scale (EDSS) and fatigue were included in the study. MSers were assigned to a one month treatment with either amantadine 200mg, ALCAR 2g, modafinil 200mg or placebo. Efficacy of the treatment was evaluated by using the modified fatigue impact scale (MFIS).
RESULTS: Sixty MSers were included in the study (39 females). The mean age of MSers was 38±6.7 years and the mean disease duration was 6.6±1.2 years. Contrast analysis showed significantly lower mean MFIS score after one month in MSers on amantadine compared to placebo (mean difference=17.3, p=0.001). There was also a trend of a lower MFIS score in ALCAR group in comparison to placebo (mean difference=12.4, p=0.05, with Keppel-corrected alpha of 0.046). The quality of life measured as SF 36 – PCS and SF 36 – MCS proved to be significantly influenced by treatment.
CONCLUSION: One month treatment with amantadine improved fatigue in MSers with relapsing-remitting MS as evaluated by MFIS. No or only a trend of improvement was seen in patients treated with modafinil or ALCAR, respectively.