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Sleep episodes in Parkinson's disease: more questions remain
Sleep Medicine 4 (2003) 267–268 www.elsevier.com/locate/sleep
Editorial
Sleep episodes in Parkinson’s disease: more questions remain
In this issue of Sleep Medicine, Roth and colleagues assessed polysomnography and multiple sleep latency tests in 24 Parkinson disease patients taking dopamine agonists who had “significant” other observed Epworth Sleepiness Scale (ESS) scores greater than 10, indicating pathologic excessive daytime sleepiness (EDS) [1]. They separated this group into those who self-reported sleep episodes (SE) and those who did not (SE2 ). In both groups, there was a reduction in nocturnal sleep efficiency (66 – 69%). The SE and SE2 groups did not differ for any variable obtained during polysomnography suggesting that patient self-report of SE did not arise from a greater degree of sleep deprivation the night prior to MSLT. Furthermore, patients who were sleepier during the day as shown by the multiple sleep latency (MSLT) score of , 5 did not differ from those with MSLT greater than 5. This study also points out that daytime sleepiness as measured by MSLT may not reflect spouse report of sleepiness and SE as determined by the ESS, as only 42% of the patients had pathological MSLT. The article also highlights the fact that pathological sleepiness as measured by MSLT may fluctuate from day to day; 40% of the patients had only one of two MSLTs indicating pathologic sleepiness. The report by Roth and colleagues provides confirmation of previous reports in several important areas [2 – 4]. First, this report finds that PD patients who are observed to have excessive daytime sleepiness (EDS) by their significant others may not self-report EDS. Second, EDS as measured by the ESS in PD does not necessarily correlate with shortened sleep latency on the MSLT. Third, PD patients with EDS may not have sufficient nocturnal sleep disturbance as measured by PSG to account for the severity of daytime sleepiness, suggesting that other factors play a role in its pathogenesis. Fourth, the sleepiest PD patients demonstrate abnormalities in REM sleep, with intrusions of REM during daytime naps. Finally, the terminology to describe the occurrence of sudden onset of sleep during the day needs to be better defined and standardized to avoid confusion when referring to this phenomenon in PD. Roth and colleagues specifically selected PD patients for inclusion in the study if they had pathological sleepiness observed by their significant others, using the Significant Other ESS score of . 10. Yet 33% of these PD patients did not report unintended sleep episodes. Unfortunately, the 1389-9457/03/$ - see front matter q 2003 Published by Elsevier B.V. doi:10.1016/S1389-9457(03)00116-3
self-reported ESS is not given for this group. Despite the omission, this finding suggests that a more accurate determination of EDS in PD is best done with both caregiver and patient input. Without caregiver observation, one-third of PD patients may be misclassified as not sleepy and not at risk for sudden sleep onset, with the potential of putting themselves at risk for unintended sleep episodes and potential injury. The second major finding of this study is that the MSLT does not distinguish between patients with and without selfreported daytime sleepiness. The MSLT is widely accepted as the ‘gold standard’ for quantifying daytime sleepiness [5]. However, an MSLT is both expensive and cumbersome, requiring a day in the sleep laboratory. The MSLT has recently been used to assess EDS in PD, although often applied to those patients referred for sleepiness. In contrast, the ESS is a simple, eight-item questionnaire scale that is completed by the patient. It measures the likelihood of dozing in various situations (e.g. while reading, while eating). The total score is obtained by summing the scores of these eight items [6]. A score greater than 10 is generally accepted as indicative of pathologic sleepiness. The ability of the ESS to measure daytime sleepiness has been debated. In two recent studies, there has been no correlation between the MSLT and the ESS score in non-Parkinsonian patients [7,8]. However, the ESS was found to correlate with a patient’s perception of problem sleepiness and with other measures of functional status and well being [9] and likely measures different aspects of daytime sleepiness not captured by the MSLT. Recently, Hobson found that elevated scores on the ESS and the Inappropriate Sleep Composite Score (ISCS) (a modification of the ESS measuring probability of dozing during active tasks such as eating, driving, working, conversing and doing household activities) was both sensitive and specific in identifying patients at risk for falling asleep while driving, suggesting that these may be more accurate tools than the MSLT in capturing the clinically important aspects of EDS in PD [10]. Roth et al.’s observation that PD patients with pathological sleepiness measured either by self-report or by MSLT did not differ in any of the PSG variables reported suggests that factors besides nocturnal sleep quality or deprivation play a role in the development of EDS in PD and
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C. Comella / Sleep Medicine 4 (2003) 267–268
confirms the observations previously made by Arnulf and Rye. Arnulf studied 54 levodopa treated PD patients (50% also receiving dopamine agonists) with EDS and found no correlation between mean sleep latency and any measure on nocturnal polysomnography [4]. Similar results were reported by Rye [3]. However, all three studies evaluated patients currently treated with dopaminergic drugs—the direct dopamine agonists, levodopa or both—and lacked a control group of sleepy non-PD elderly. Hence, distinguishing between EDS related directly to the disease process versus EDS arising as side effects of antiparkinson medications is not addressed. Further studies assessing EDS in untreated PD and using an appropriate control group may clarify this important issue. One of the more intriguing phenomena found in PD is the occurrence of REM during daytime MSLT nap opportunities. Roth found that 29% of the patients evaluated had REM onsets and that these patients were sleepier on MSLT. Rye described REM onset naps in 22% of the 27 PD patients evaluated [3]. Arnulf observed REM onset naps in 30% of 20 PD patients assessed, with all but one having daytime hallucinations. Daytime hallucinations were observed to be associated with REM onsets [2]. The common feature in all three studies is that the patients with REM onset naps were sleepier during the day than those without. The occurrence of REM sleep during the MSLT is a characteristic finding in narcolepsy, with EDS and hypnogogic and hypnopompic hallucinations as additional clinical characteristics. Taken together, these three studies strongly suggest that there is a subgroup of PD patients with a narcoleptic like phenotype. The factors that distinguish this subgroup may provide important insights into the pathogenic mechanisms of EDS and dopaminergic hallucinations in PD. Finally, the study by Roth et al. emphasizes the need for a definition and standardization of terminology related to the episodes of sudden, unexpected onset of sleep without ambient drowsiness and dozing off with drowsiness. Roth uses the term ‘undesired sleep episodes’, defined as falling asleep in inappropriate situations or at unwanted times. Whether these are sudden or gradual onset is not clarified. The term ‘sleep attacks’ has been defined as ‘an event of overwhelming sleepiness that occurs without warning, or that occurs with a prodrome that is sufficiently short or overpowering to prevent the patient from taking appropriate protective measures’ [11]. This term has been criticized with the argument that sudden sleep arises from drowsiness for which the patient may be amnestic [12]. However, the transition in a PD patient from wakefulness to stage 2 sleep within a 10-second time span has been shown using polysomnography, indicating that sudden sleep onset may occur without warning [13]. The concept that PD patients may suddenly sleep without warning appears to be a rare phenomenon [10] but carries with it serious implications
for driving and engaging in other potentially dangerous activities. Comparisons of results among studies assessing EDS and sleep episodes in PD can only be done if the terminology utilized is consistent across studies. Finally, as is acknowledged by the investigators, it is important to recognize that these study results are only applicable to the particular group of patients assessed, namely, sleepy PD patients treated with dopaminergic drugs. Lacking a control group, it may be that these findings are not specific for PD, but may also be found in other sleepy elderly groups. Future investigations into the sleep problems of PD patients will help to clarify whether there is a unique aspect of EDS in PD that is intrinsic to the disease process or its treatments.
References [1] Roth T, Rye DB, Borchert LD et al. Assessment of sleepiness and unintended sleep in Parkinson’s disease patients taking dopamine agonists. Sleep Med S1389-9457(03)00068-3. [2] Arnulf I, Bonnet AM, Damier P, allucinations REM, et al. sleep, and Parkinson’s disease. A medical hypothesis. Neurology 2000;55: 281 –8. [3] Rye DB, Bliwise DL, Dihenia B, et al. Daytime sleepiness in Parkinson’s disease. J Sleep Res 2000;9:63–9. [4] Arnulf I, Konofal E, Merino-Amdreu M, et al. Parkinson’s disease and sleepiness. An integral part of PD. Neurology 2002;58:1019 –24. [5] Carskadon MA, Dement WK, Mitler MM, et al. Guidelines for the multiple sleep latency tests (MSLT): a standard measure of sleepiness. Sleep 1986;9:519– 24. [6] Johns MW. A new Method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991;14:540 –5. [7] Benbadis SR, Mascha E, Perry MC, et al. Association between the Epworth Sleepiness Scale and the Multiple Sleep Latency Test in a clinical population. Ann Intern Med 1999;130:289– 92. [8] Chervin RD, Aldrich MS. The Epworth Sleepiness Scale may not reflect objective measures of sleepiness or sleep apnea. Neurology 1999;52:125–31. [9] Briones N, Adams N, Strauss M, et al. Relationship between sleepiness and general health status. Sleep 1996;19:583–8. [10] Hobson DE, Lang AE, Martin WR, et al. Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease. A survey by the Canadian movement disorders group. J Am Med Assoc 2002;287: 455 –63. [11] Frucht SJ, Greene PE, Fahn S. Sleep episodes in Parkinson’s disease: a wake up call. Mov Disord 2000;15:601–3. [12] Olanow CW, Schapira AHV, Roth T. Waking up to sleep episodes in Parkinson’s disease. Mov Disord 2000;15:212– 5. [13] Tracik F, Ebersbach G. Sudden daytime sleep onset in Parkinson’s disease: Polysomnographic recordings. Mov Disord 2001;16:500–6.
Cynthia Comella Departments of Neurological Sciences and Psychology, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL, USA Received 8 May 2003; Accepted 8 May 2003
Editorial
Sleep episodes in Parkinson’s disease: more questions remain
In this issue of Sleep Medicine, Roth and colleagues assessed polysomnography and multiple sleep latency tests in 24 Parkinson disease patients taking dopamine agonists who had “significant” other observed Epworth Sleepiness Scale (ESS) scores greater than 10, indicating pathologic excessive daytime sleepiness (EDS) [1]. They separated this group into those who self-reported sleep episodes (SE) and those who did not (SE2 ). In both groups, there was a reduction in nocturnal sleep efficiency (66 – 69%). The SE and SE2 groups did not differ for any variable obtained during polysomnography suggesting that patient self-report of SE did not arise from a greater degree of sleep deprivation the night prior to MSLT. Furthermore, patients who were sleepier during the day as shown by the multiple sleep latency (MSLT) score of , 5 did not differ from those with MSLT greater than 5. This study also points out that daytime sleepiness as measured by MSLT may not reflect spouse report of sleepiness and SE as determined by the ESS, as only 42% of the patients had pathological MSLT. The article also highlights the fact that pathological sleepiness as measured by MSLT may fluctuate from day to day; 40% of the patients had only one of two MSLTs indicating pathologic sleepiness. The report by Roth and colleagues provides confirmation of previous reports in several important areas [2 – 4]. First, this report finds that PD patients who are observed to have excessive daytime sleepiness (EDS) by their significant others may not self-report EDS. Second, EDS as measured by the ESS in PD does not necessarily correlate with shortened sleep latency on the MSLT. Third, PD patients with EDS may not have sufficient nocturnal sleep disturbance as measured by PSG to account for the severity of daytime sleepiness, suggesting that other factors play a role in its pathogenesis. Fourth, the sleepiest PD patients demonstrate abnormalities in REM sleep, with intrusions of REM during daytime naps. Finally, the terminology to describe the occurrence of sudden onset of sleep during the day needs to be better defined and standardized to avoid confusion when referring to this phenomenon in PD. Roth and colleagues specifically selected PD patients for inclusion in the study if they had pathological sleepiness observed by their significant others, using the Significant Other ESS score of . 10. Yet 33% of these PD patients did not report unintended sleep episodes. Unfortunately, the 1389-9457/03/$ - see front matter q 2003 Published by Elsevier B.V. doi:10.1016/S1389-9457(03)00116-3
self-reported ESS is not given for this group. Despite the omission, this finding suggests that a more accurate determination of EDS in PD is best done with both caregiver and patient input. Without caregiver observation, one-third of PD patients may be misclassified as not sleepy and not at risk for sudden sleep onset, with the potential of putting themselves at risk for unintended sleep episodes and potential injury. The second major finding of this study is that the MSLT does not distinguish between patients with and without selfreported daytime sleepiness. The MSLT is widely accepted as the ‘gold standard’ for quantifying daytime sleepiness [5]. However, an MSLT is both expensive and cumbersome, requiring a day in the sleep laboratory. The MSLT has recently been used to assess EDS in PD, although often applied to those patients referred for sleepiness. In contrast, the ESS is a simple, eight-item questionnaire scale that is completed by the patient. It measures the likelihood of dozing in various situations (e.g. while reading, while eating). The total score is obtained by summing the scores of these eight items [6]. A score greater than 10 is generally accepted as indicative of pathologic sleepiness. The ability of the ESS to measure daytime sleepiness has been debated. In two recent studies, there has been no correlation between the MSLT and the ESS score in non-Parkinsonian patients [7,8]. However, the ESS was found to correlate with a patient’s perception of problem sleepiness and with other measures of functional status and well being [9] and likely measures different aspects of daytime sleepiness not captured by the MSLT. Recently, Hobson found that elevated scores on the ESS and the Inappropriate Sleep Composite Score (ISCS) (a modification of the ESS measuring probability of dozing during active tasks such as eating, driving, working, conversing and doing household activities) was both sensitive and specific in identifying patients at risk for falling asleep while driving, suggesting that these may be more accurate tools than the MSLT in capturing the clinically important aspects of EDS in PD [10]. Roth et al.’s observation that PD patients with pathological sleepiness measured either by self-report or by MSLT did not differ in any of the PSG variables reported suggests that factors besides nocturnal sleep quality or deprivation play a role in the development of EDS in PD and
268
C. Comella / Sleep Medicine 4 (2003) 267–268
confirms the observations previously made by Arnulf and Rye. Arnulf studied 54 levodopa treated PD patients (50% also receiving dopamine agonists) with EDS and found no correlation between mean sleep latency and any measure on nocturnal polysomnography [4]. Similar results were reported by Rye [3]. However, all three studies evaluated patients currently treated with dopaminergic drugs—the direct dopamine agonists, levodopa or both—and lacked a control group of sleepy non-PD elderly. Hence, distinguishing between EDS related directly to the disease process versus EDS arising as side effects of antiparkinson medications is not addressed. Further studies assessing EDS in untreated PD and using an appropriate control group may clarify this important issue. One of the more intriguing phenomena found in PD is the occurrence of REM during daytime MSLT nap opportunities. Roth found that 29% of the patients evaluated had REM onsets and that these patients were sleepier on MSLT. Rye described REM onset naps in 22% of the 27 PD patients evaluated [3]. Arnulf observed REM onset naps in 30% of 20 PD patients assessed, with all but one having daytime hallucinations. Daytime hallucinations were observed to be associated with REM onsets [2]. The common feature in all three studies is that the patients with REM onset naps were sleepier during the day than those without. The occurrence of REM sleep during the MSLT is a characteristic finding in narcolepsy, with EDS and hypnogogic and hypnopompic hallucinations as additional clinical characteristics. Taken together, these three studies strongly suggest that there is a subgroup of PD patients with a narcoleptic like phenotype. The factors that distinguish this subgroup may provide important insights into the pathogenic mechanisms of EDS and dopaminergic hallucinations in PD. Finally, the study by Roth et al. emphasizes the need for a definition and standardization of terminology related to the episodes of sudden, unexpected onset of sleep without ambient drowsiness and dozing off with drowsiness. Roth uses the term ‘undesired sleep episodes’, defined as falling asleep in inappropriate situations or at unwanted times. Whether these are sudden or gradual onset is not clarified. The term ‘sleep attacks’ has been defined as ‘an event of overwhelming sleepiness that occurs without warning, or that occurs with a prodrome that is sufficiently short or overpowering to prevent the patient from taking appropriate protective measures’ [11]. This term has been criticized with the argument that sudden sleep arises from drowsiness for which the patient may be amnestic [12]. However, the transition in a PD patient from wakefulness to stage 2 sleep within a 10-second time span has been shown using polysomnography, indicating that sudden sleep onset may occur without warning [13]. The concept that PD patients may suddenly sleep without warning appears to be a rare phenomenon [10] but carries with it serious implications
for driving and engaging in other potentially dangerous activities. Comparisons of results among studies assessing EDS and sleep episodes in PD can only be done if the terminology utilized is consistent across studies. Finally, as is acknowledged by the investigators, it is important to recognize that these study results are only applicable to the particular group of patients assessed, namely, sleepy PD patients treated with dopaminergic drugs. Lacking a control group, it may be that these findings are not specific for PD, but may also be found in other sleepy elderly groups. Future investigations into the sleep problems of PD patients will help to clarify whether there is a unique aspect of EDS in PD that is intrinsic to the disease process or its treatments.
References [1] Roth T, Rye DB, Borchert LD et al. Assessment of sleepiness and unintended sleep in Parkinson’s disease patients taking dopamine agonists. Sleep Med S1389-9457(03)00068-3. [2] Arnulf I, Bonnet AM, Damier P, allucinations REM, et al. sleep, and Parkinson’s disease. A medical hypothesis. Neurology 2000;55: 281 –8. [3] Rye DB, Bliwise DL, Dihenia B, et al. Daytime sleepiness in Parkinson’s disease. J Sleep Res 2000;9:63–9. [4] Arnulf I, Konofal E, Merino-Amdreu M, et al. Parkinson’s disease and sleepiness. An integral part of PD. Neurology 2002;58:1019 –24. [5] Carskadon MA, Dement WK, Mitler MM, et al. Guidelines for the multiple sleep latency tests (MSLT): a standard measure of sleepiness. Sleep 1986;9:519– 24. [6] Johns MW. A new Method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991;14:540 –5. [7] Benbadis SR, Mascha E, Perry MC, et al. Association between the Epworth Sleepiness Scale and the Multiple Sleep Latency Test in a clinical population. Ann Intern Med 1999;130:289– 92. [8] Chervin RD, Aldrich MS. The Epworth Sleepiness Scale may not reflect objective measures of sleepiness or sleep apnea. Neurology 1999;52:125–31. [9] Briones N, Adams N, Strauss M, et al. Relationship between sleepiness and general health status. Sleep 1996;19:583–8. [10] Hobson DE, Lang AE, Martin WR, et al. Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease. A survey by the Canadian movement disorders group. J Am Med Assoc 2002;287: 455 –63. [11] Frucht SJ, Greene PE, Fahn S. Sleep episodes in Parkinson’s disease: a wake up call. Mov Disord 2000;15:601–3. [12] Olanow CW, Schapira AHV, Roth T. Waking up to sleep episodes in Parkinson’s disease. Mov Disord 2000;15:212– 5. [13] Tracik F, Ebersbach G. Sudden daytime sleep onset in Parkinson’s disease: Polysomnographic recordings. Mov Disord 2001;16:500–6.
Cynthia Comella Departments of Neurological Sciences and Psychology, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL, USA Received 8 May 2003; Accepted 8 May 2003