Fatigue and daytime sleepiness in patients with myotonic dystrophy type 1: To lump or split?

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Abstract

We assessed the relationship and clinical correlates of fatigue and Excessive Daytime Sleepiness (EDS) in 200 myotonic dystrophy type 1 (DM1) patients by means of questionnaire and neuropsychological evaluation. Fatigue levels were higher in patients with EDS and daytime sleepiness levels higher in patients with excessive fatigue. However, EDS without fatigue was rarely observed. Also, DM1 patients with fatigue (with or without EDS) showed greater muscular impairment, CTG repeats, abnormalities regarding personality, depressive symptoms and lower health-related quality of life (HRQoL) than patients without these symptoms. These findings do not readily support the contention that fatigue and EDS constitute distinct clinical manifestations in DM1. Clinicians should systematically evaluate both symptoms since fatigue and EDS have a greater impact on HRQoL than fatigue alone. However, specific rating scales for fatigue in DM1 have yet to be devised.

Introduction

Myotonic dystrophy type 1 (DM1), an autosomal dominant disorder, is the most common adult form of muscular dystrophy [1]. DM1 results from an unstable CTG repeat expansion in the 3′ untranslated region of the myotonic dystrophy protein kinase (DMPK) gene at 19q13.3 [2]. It is not only a muscle disease but a multisystemic disorder, including impairment of the central nervous system [1]. Excessive Daytime Sleepiness (EDS) has long been associated with DM1 and has been referred as the patients’ most frequent non-muscular symptom [3]. It may be apparent as one of the earliest symptoms of the disorder, with many patients complaining of EDS for years before DM1 is diagnosed [4], [5], [6]. With virtually all systems of the body affected in some way, the causes of EDS in DM1 are potentially multifactorial. However, available evidence is in favor of EDS being due to a specific central mechanism unrelated to respiratory drive [7], [8], [9]. In addition, fatigue is more common in DM1 than in other neuromuscular disorders and can, alike EDS, reportedly be salient in some patients with only mild muscular impairment [1], [10]. While DM1 is recognized as a neurological disorder causing central fatigue [11], not much is known about its clinical characteristics, mechanisms, and therapeutics.

Although the terms fatigue and sleepiness are often used interchangeably, they should be differentiated [12] since they may constitute two distinct, albeit interrelated symptoms [13]. In DM1, the first of two studies that assessed the relationship of fatigue to daytime sleepiness detected no significant association but mentioned that the sample of 36 patients was insufficient to confidently exclude the absence of an effect [5]. More recently, a study of 32 consecutive ambulant patients revealed that fatigue scores were increased irrespectively of the presence of daytime sleepiness and that both these symptoms were unrelated to disease severity, suggesting different pathophysiological mechanisms [14]. A frequent lesson in medical education relates daytime sleepiness complaints to a potential sleep disorder, and complaints of fatigue, tiredness, or lack of energy to psychiatric or medical diagnoses [15]. As regards DM1, one may contend that fatigue has an indirect cause that is not specifically related to the disease process but secondary to other possible consequences of DM1, such as sleep disturbances or depression. In view of the specific pathways for evaluating and treating EDS [16], [17] and central fatigue [11], on the one hand, and of the heavy toll that both these symptoms exact upon physical and social functioning of DM1 patients [1], [5], [10], [18], on the other, it was deemed important to investigate further their clinical characteristics in this condition.

This study aims to document whether age, gender, body mass index (BMI), degree of muscular impairment, and CTG repeats are related to daytime sleepiness and fatigue, as assessed by standardized rating scales, and to assess the relationship between these latter symptoms. In an effort to augment our understanding of potential correlates and outcomes of fatigue and daytime sleepiness in DM1, we also explored the association of fatigue and daytime sleepiness to sleep-related complaints, habitual sleep duration, personality patterns, intensity of depressive symptoms, Intellectual Quotient (IQ), and Health-Related Quality of Life (HRQoL).

Section snippets

Methods

The study cohort included two-hundred patients with adult DM1 (79 men, 121 women; 47.0 ± 11.8 years, range 20–81) followed at the Neuromuscular Clinic of the Centre de Santé et de Services Sociaux (CSSS) de Jonquière (Québec, Canada). Patients with congenital and infantile forms of DM1 were excluded. All patients were examined by a neurologist and had their muscular impairment categorized according to the Muscular Impairment Rating Scale (MIRS) [19]: grade 1 (no sign of muscular impairment, n = 

Fatigue and daytime sleepiness levels

The mean (SD) scores were 8.1 (5.0) for ESS, 4.9 (3.0) for DSS, 4.6 (1.7) for FSS, and 5.1 (2.6) for VAS. The proportion of DM1 patients with EDS is 30.0% according to the ESS and 30.5% according to the DSS. The proportion of DM1 patients with excessive fatigue is 62.5% according to the FSS. Table 1 presents the relationships between fatigue and daytime sleepiness scores of DM1 patients on the four scales used herein. More specifically, the use of validated cutoff scores showed that DM1

Discussion

This study assesses the relationship of fatigue to daytime sleepiness in a large sample of patients affected by DM1 and confirms the unequivocal presence of these symptoms in this condition. Indeed, about 60% and 30% of patients reported fatigue and EDS, in accordance with previous estimates based on samples unselected with regards to these symptoms [5], [10], [14], [22]. It is noteworthy that the prevalence of fatigue doubles that of EDS. In the field of sleep medicine, the incongruence of

Competing interests

The authors report no conflict of interests.

Acknowledgements

This research was supported by the Neuromuscular Partnership Program of Muscular Dystrophy Canada, the Canadian Institutes of Health Research (CIHR) (#MOP49556) and ECOGENE-21, a research program in community genetics and genomics supported by the Canada Research Chairs Program and the CIHR (#CAR43283), and by the Fonds de la Recherche en Santé du Québec (S.J.).

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