Medical Comorbidity of Sleep Disorders

Dimitris Dikeos; Georgios Georgantopoulos


Curr Opin Psychiatry. 2011;24(4):346-354. 

In This Article

Hypersomnias and Excessive Daytime Sleepiness

All hypersomnias are characterized by the presence of EDS, one of the most commonly reported symptoms concerning sleep. The diminished alertness, attention and concentration that accompany EDS increase significantly the risk of occupational and motor vehicle accidents.[83–85] Validated questionnaires as the Epworth Sleepiness Scale (ESS) and the Stanford Sleepiness Scale (SSS) are used in order to assess EDS, whereas laboratory evaluation of sleep by methods such as all-night Polysomnography (PSG), Multiple Sleep Latency Test (MSLT) or Maintenance of Wakefulness Test (MWT) is used to objectively evaluate reduced alertness and excessive sleepiness, and to assist in the identification of their cause(s).[85]

EDS can be a result of a number of intrinsic or extrinsic conditions.[85,86,87•] It can be due to one of the primary hypersomnias [narcolepsy, idiopathic hypersomnia and recurrent hypersomnia (Kleine–Levin syndrome)]; insufficient sleep time due to lifestyle and sleep habits, shift work, circadian rhythm disorders or other conditions characterized by reduced night-sleep (such as fragmented sleep, sleep apnoea, RLS or PLMS); and secondary to psychiatric disorders, medications (benzodiazepines, antidepressants, antipsychotics, antihistamines, opioids, beta-blockers, etc.) and certain medical conditions.[85,86,87•]


Narcolepsy is the main idiopathic condition causing EDS. It can be primary (associated with the HLA DQB1*0602 allele) or secondary resulting from neurological disorders and other conditions affecting the central nervous system (CNS), such as brain tumours (especially diencephalic and midbrain ones), stroke, multiple sclerosis, cerebral trauma or encephalitis.[88,89•,90] Furthermore, the risk of narcolepsy in the presence of a history of streptococcal throat infection before the age of 21 years was estimated to be 5.4 times higher, suggesting that rheumatic fever might induce narcolepsy, probably in a similar manner as it does Syndenham's chorea.[91,92] The risk for narcolepsy was also found to be increased (OR = 5.1) for individuals who had lived with two or more household smokers (a factor known to aggravate strep-throat infections) before age 21; the finding was more pronounced among genetically susceptible individuals bearing the HLA narcolepsy-associated haplotype.[92]

Hypersomnia in Other Neurological Disorders

EDS seems to be quite prominent among Parkinson's disease patients, with a frequency ranging from 8% to more than 50% in various studies.[31••,93,94] Considering the association of EDS with Parkinson's disease, it has been suggested that the reason behind the EDS might be the neurodegenerative mechanism itself (including dopamine pathways and other neurochemical components of the ascending reticular activation system) and/or the various drugs used.[95] Indeed, a multicentre control study on Japanese patients provided data suggesting that sleepiness in Parkinson's disease is dependent on the disease itself and on the dopaminergic treatment rather than nocturnal disturbances.[96] EDS, in addition, was found to be a predictor for the development of Parkinson's disease in a large cohort of more than 3000 older men followed for 7 years.[97] In another study among 30 consecutive patients with Parkinson's disease examined in the sleep laboratory by MSLT, 57% had an ESS score greater than 10 and 37% had a mean sleep latency of less than 5 min during the MSLT; none of these patients exhibited a sleep onset REM episode, indicating that their hypersomnia was not due to comorbid narcolepsy.[94]

In addition to Parkinson's disease, neurological diseases that are frequently found among patients with EDS include various other neurodegenerative disorders (dementias, Huntington's disease, progressive supranuclear palsy, multiple sclerosis, spinocerebellar ataxia), stroke, epilepsy, structural brain lesions (TBI or brain tumours, especially diencephalic, midbrain, hypothalamic, pituitary), infections of the CNS (especially African trypanosomiasis and encephalitis lethargica) and neuromuscular diseases (including myasthenia gravis, polyneuropathies, poliomyelitis, etc.).[85,87•,88,89•,98–101]

Hypersomnia in Other Medical Disorders

Regarding the comorbidity of EDS with nonneurological medical disorders, in a study of consecutively recruited adult type 2 diabetic patients, the proportion of diabetic patients with elevated ESSs (> or =12) was higher than that of the controls (15.5 vs. 2.1%, P = 0.02).[19] A secondary analysis on individuals drawn from the National Sleep Foundation's Sleep and Aging poll indicated that sleep disturbances affect not only sleep quality but also daytime function in older adults with diabetes;[102] in another study, although the association between glycated haemoglobin (HbA1c) values and ESS score has been found to be significant, the causality of the effect was considered to be uncertain, as hypersomnolence in diabetic patients may be mediated by RLS, nocturia or snoring/OSAS.[103] OSAS patients suffer frequently from hypersomnolence; concomitant presence of diabetes, cardiovascular disease or depression is associated with persistence of daytime sleepiness even after the successful treatment of sleep apnoeas by C-PAP.[104] In a study evaluating the sleep/wake cycle of individuals with asthma, it was concluded that asthma, as a chronic inflammatory disease, can affect daytime wakefulness;[105] furthermore, data on 470 asthmatic patients indicated that women were much more likely to exhibit EDS than men.[106] EDS in renal dialysis patients has been shown to be correlated with higher blood urea nitrogen (BUN), high frequency of PLM and sleep apnoea.[107–109] Other medical disorders associated with EDS are rheumatological, respiratory, cardiovascular, urinary (such as lower urinary tract symptoms or any other disorders associated with nocturia), malignancy and general fatigue.[85,87•,88,110–113]

In a study examining the relationship of EDS with common medical disorders in an unselected community-based sample, the authors assessed responses of 2612 individuals (aged 18–65) after excluding shift workers and those with suspected sleep disordered breathing or narcolepsy. Participants across a range of medical disorders were evaluated using the ESS and patient reports of nocturnal sleep. Individuals with ulcers [OR = 2.21, 95% confidence interval (CI) = 1.35–3.61] and migraine (OR = 1.36, 95% CI = 1.08–1.72) were shown to have independently and clinically significantly higher levels of EDS relative to other common medical disorders.[114•]

Relationship of Hypersomnia with General Morbidity and Mortality

Finally, a relationship seems to exist between EDS and general morbidity and mortality. In the National Health Interview Survey 2005, a cross-sectional study of 30 397 participants, it was demonstrated that there is a positive association between daily sleep being longer than 9 h and cardiovascular disease, compared with sleep duration of 7 h per day (OR = 1.57, 95% CI = 1.31–1.89).[115••] Similarly, in a cohort study on 98 634 participants in Japan (the Japan Collaborative Cohort study), it was concluded that long sleep duration (>10 h) was associated with 1.5 to two-fold increase of mortality from stroke, total cardiovascular disease and other causes of death except cancer, suggesting that, although mechanisms are not clear, long sleep duration may be an early symptom of various disorders with high mortality rates.[116]


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