“Balm of hurt minds, great nature’s second course, chief nourisher in life’s feast.” That is how William Shakespeare described sleep in Macbeth (1623). Yet this vital process can be disrupted, leaving individuals exhausted, drained, and unrefreshed. People with MS are particularly vulnerable to sleep disturbances, which can be challenging to assess due to overlapping symptoms. Importantly, although most people with MS report sleep disturbances when asked, only a minority have ever discussed these issues with their healthcare providers [1].
Fatigue, sleepiness, and depression
“I am tired” is a phrase that neurologists frequently hear from individuals with MS. But what might lie beneath this statement? What should be investigated further? Affecting up to 87.5% of individuals with MS, fatigue is one of the most common and debilitating MS symptoms that can profoundly interfere with daily activities and reduce quality of life [2]. This sense of lack of energy and tiredness can also be associated with sleep disorders [3]. Indeed, treating sleep disorders can alleviate both fatigue and sleepiness [4].
Dr Anne-Laure Dubessy, from the AP-HP, Assistance Publique – Hôpital Pitié Salpétrière in Paris, tells us, “Sleepiness and fatigue are two distinct concepts, yet they can overlap, with common symptoms that can be difficult to distinguish.”
A holistic approach that considers a cluster of symptoms, rather than focusing on just one, can make the difference in clinical assessment, as Professor Daphne Kos highlighted at ECTRIMS 2024. In fact, fatigue can also overlap with depression. And once more, this can be challenging, as both conditions share symptoms, such as lack of energy, disrupted sleep, reduced interest (anhedonia), and difficulties with concentration [5]. Individuals with MS who experience sleepiness or depression nearly always report fatigue as well, but the reverse is not true – some individuals with MS suffer solely from fatigue [6].
The red flags of sleep disorders
Dr Dubessy emphasises, “Before recommending polysomnographic studies for everyone, it is essential to screen properly. Some individuals with MS experience authentic fatigue, while others may experience fatigue as a result of sleep disorders. Asking the right questions is crucial to determine whether a more in-depth interview about sleep disorders is warranted. The Epworth Sleepiness Scale (ESS) is a quick and easy tool that can aid in screening. Moreover, it is important to ask whether sleep habits have changed following the onset of MS. Individuals with MS who suffers from sleep disorders may say, ‘Since I developed MS, my sleep has changed, and I feel tired’ or ‘I need to go to bed earlier, wake up later, sleep longer, and still don’t feel refreshed.’ Another key question concerns the need to rest. I often ask, ‘When you rest, do you tend to fall asleep, or do you just feel physically tired?’. Sleepiness is not merely what one might commonly expect, such as feeling tired in the early afternoon – this is normal and happens to everyone. While it’s typical to feel sleepy around 14:00 and perhaps take a nap, it is not normal to feel sleepy during times when we should be alert according to our circadian rhythm, such as around 11:00 or 18:00. Finally, experiencing major difficulties waking up or describing a subjective feeling of hypoarousal and mental cloudiness lasting more than 30 minutes after waking is suggestive of “sleep inertia,” a symptom of hypersomnia. Such occurrences are a red flag.”
Sleep disturbances in individuals with MS
“The first step is to check for any MS-related symptoms that may interfere with sleep continuity, as these can intertwine with insomnia”, Dr Dubessy tells us.
Pain, spasticity, bladder control issues, and anxiety are chronic symptoms related to MS that can disrupt sleep [7]. At least 40% of individuals with MS suffer from chronic insomnia, characterised by difficulties in falling asleep, maintaining sleep, or waking up too early [8].
Restless legs syndrome, which involves an urge to move the legs during periods of rest, followed by sleep apnea, is among the most prevalent sleep disorders in individuals with MS [9, 10]. Sleep apnea occurs when the upper airway is partially or completely blocked multiple times during sleep, leading to daytime fatigue, mood swings, cognitive dysfunction, and a diminished quality of life [11].
Additionally, sleep disorders can include central disorders of hypersomnolence, which are characterised by excessive daytime sleepiness, such as narcolepsy and idiopathic hypersomnia.
“The narcolepsy-type phenotype is quite prototypical. Common symptoms encompass sleep attacks, short refreshing naps, disturbed night sleep, and symptoms related to the rapid eye movement (REM) phase, such as sleep paralysis, hallucinations, and cataplexy. However, even individuals exhibiting all the symptoms of narcolepsy may not receive an accurate diagnosis until 7 to 10 years after the onset of symptoms. This shows that detecting the condition may not always be straightforward. Some individuals with MS present with a hypersomnia-like phenotype, which closely resembles idiopathic hypersomnia. In this case, individuals don’t fall asleep unexpectedly during the day. After a full night’s sleep, they may still feel unrefreshed and struggle to wake up in the morning. Individuals with a hypersomnia-like phenotype may feel more tired, “au radar”, as one would say in French, not fully alert, and operate on autopilot, functioning in a suboptimal manner. I visited a woman with MS who had previously managed her life rather well with three kids. She shared that after MS onset, she began to have serious trouble waking up and getting her children to school. She often needed to return home and sleep until noon. After treatment, her situation improved. However, prescribing stimulant treatments must be contingent on a proper diagnosis of sleep disorder. Indeed, one of the leading causes of daytime sleepiness in the general population, particularly among young adults, is «insufficient sleep syndrome», which results from chronic sleep deprivation due to poor sleep hygiene. In such cases, administering stimulants is not a good strategy. Hypersomnia must be clearly established before treatment.”
A polysomnographic study shows that 53% of individuals with MS who report fatigue and sleepiness suffer from central hypersomnia [12]. Interestingly, the study also reveals that restless leg syndrome, periodic leg movements, and sleep apnea occur with similar frequency in the general population and in individuals with MS [12].
Behavioral interventions to manage insomnia
Drug treatment options are available to address sleep disorders. After diagnosing sleep disturbances and a thoroughly analysing the contributing factors, a multidisciplinary approach is needed to address these factors and tailor interventions for each individual.
“Some sleep-related disorders may be due to MS-related lesions, some may be related to MS symptoms, some of them are behavioral. For example, insomnia is rather behavioral and responds well to cognitive behavioral therapy, which can improve sleep quality and reduce anxiety [8]”, Dr Laura Laslett from the University of Tasmania tells us.
“We can help individuals with MS manage their sleep more effectively.” Professor Abbey Hughes from the Johns Hopkins University. “Understanding the causes of sleep disturbances is key. Sometimes multifaceted factors can contribute to poor sleep. For example, I had a patient with fatigue, pain, depressive mood, and signs of disease progression. She had increased nighttime worries – about keeping track of medications, appointments, and work stress – that interfered with sleep. She also used stimulant medications and caffeine, which made it harder to fall asleep. We worked with a cognitive behavioral therapist to limit her time in bed to the hours she was actually asleep. People who cannot sleep well often go to bed too early due to their fatigue or to get more sleep. Unfortunately, this can worsen insomnia, as you cannot initiate sleep if you are not ready to sleep. Instead, we encouraged relaxing activities in the evening to help adjust the sleep routine. Psychotherapy helped address her worries and we developed strategies to manage fatigue and stress during the day.”
***
Written by Stefania de Vito
Special thanks to Dr Anne-Laure Dubessy (AP-HP, Assistance Publique – Hôpital Pitié Salpétrière), Dr Laura Laslett (University of Tasmania), and to Professor Abbey Hughes (Johns Hopkins University) for their insights.
References
[1] Brass, SD, Li C-S, and Auerbach S. JCSM 2014; 10(9): 1025-1031.
[2] Marchesi O et al. Expert Rev. Neurother. 2022; 22(8): 681-693.
[3] Veauthier C et al. Mult. Scler. J. 2011; 17(5): 613-622.
[4] Côté I et al. Mult. Scler. J. 2013; 19(4): 480-489.
[5] Billones, RR, Kumar S, and Saligan LN. 2020; Transl. Psychiatry 10(1): 273.
[6] Sparasci D et al. J. Neurol. 2022; 269(9): 4961-4971.
[7] Hensen HA, Krishnan AV, Eckert DJ. Front. Neurol. 2018; 8: 740.
[8] Siengsukon CF, Beck ES, & Drerup M IJMSC 2021; 23(3): 107-113.
[9] Manconi, Mauro, et al. Nat. Rev. Dis. Primers 2021; 7(1): 80.
[10] Marrie RA et al. Mult. Scler. J. 2015; 21(3): 342-349.
[11] Singh M et al. Mult. Scler. J. 2022; 28(2): 280-288.
[12] Dubessy A-L et al. Neurol. 2021; 97(1): e23-e33.