Sudden-Onset Sleep in Parkinson’s Disease: Who is at Risk?

Abstract & Commentary

Synopsis: SOS, in part, can be attributed to PD-specific pathology because disease duration and subjective disease severity have been shown to be predictors of SOS.

Sources: Korner,Y et al. Predictors of Sudden Onset of Sleep in Parkinson's Disease. Movement Disorders. 2004;19:1298-1305; Rissling I, et al. Dopamine Receptor Gene Polymorphisms in Parkinson's Disease Patients Reporting "Sleep Attacks". Movement Disorders. 2004;19:1279-1284.

Sudden onset of sleep (SOS) can occur in people with Parkinson's disease (PD), and has potentially disastrous consequences, especially while driving. Sleep attacks were initially reported in patients taking non-ergoline dopamine agonists.1 However, other medications, as well as characteristics of the disease itself, have since been implicated, and how to identify those at risk remains controversial. Two studies recently attempted to address this question and investigate a relationship to dopamine dysfunction, in very different ways. Korner and colleagues targeted 12,000 members of a nationwide German PD patient support group, with a questionnaire designed specifically for this study. The questionnaire contained items regarding disease duration and medications, the Epworth Sleepiness Scale, as well as sleep behavior at night and during the daytime. SOS was assessed based upon subjective responses to a set of questions, without the need for eyewitness account. Of 6620 respondents with PD, 42.9% reported SOS. Of these, fully 10% did not think they experienced prior warning symptoms of drowsiness. The strongest predictors of SOS were increasing age, male sex, longer disease duration, and presence of various sleep disturbances. Taking non-ergoline dopamine agonists was more strongly associated with SOS in patients below 70 years old and in those with disease duration less than 7 years. To further address a potential role for dopaminergic agents, 137 patients with SOS and 137 patients without SOS were identified from respondents by Rissling and colleagues. Blood was drawn for genetic analysis by each patient's general practitioner, and was subjected to testing for known polymorphisms in the dopamine D2 receptor family. A Taq IA polymorphism in DRD2 was significantly associated with SOS. No significant differences were observed for polymorphisms in the DRD3 and DRD4 genes.

Commentary

Daytime somnolence is a serious problem for many with PD. Brainstem pathology in PD likely impacts on sleep-wake disturbances, through dysfunction of mesocorticolimbic (and possibly mesostriatal) circuitry that contributes to wakefulness, as well as involvement of other structures such as the pedunculopontine nucleus (PPN). A Canadian study, performed by direct evaluation and interview, found 51% of highly functional, non-demented PD patients to have excessive daytime sleepiness.2 Almost 4% of those still driving had experienced at least 1 episode of falling asleep at the wheel, and some patients report sleep attacks, without warning signs of prior drowsiness. The issue is complicated by the possibility that any warning signs may be misjudged or later forgotten by patients. How then, should we counsel our patients about these occurrences? Identifying associations via observational studies is a first step. The study design utilized by Korner et al is, of course, subject to bias: we cannot be sure that respondents indeed have idiopathic PD, those with daytime drowsiness might be more likely to respond, and subjective reports in this realm are quite unreliable. However, associations of age, male sex, and disease duration, demonstrated in this study, are plausible, and are consistent with those noted previously. The study also highlights a potential contribution of dopaminergic medications. Dopamine plays a complex role in normal and pathologic sleep-wake cycles, and anti-Parkinson's medications can negatively impact both nighttime sleep and daytime alertness. How this occurs is unclear, but non-ergoline dopamine agonists have negligible binding to the dopamine D1 receptor family. Rissling et al, therefore, sought to concentrate efforts on the D2 receptor family. It is intriguing that association of a DRD2 gene polymorphism with SOS was demonstrated in this population. This needs to be confirmed, but could be a first step to better understanding the molecular underpinnings of abnormalities of sleep and wakefulness in PD. For the present, questioning about sleep habits and daytime drowsiness should be part of our clinical evaluation of a PD patient, with careful counseling and monitoring when it comes to choice of medication. — Claire Henchcliffe

Dr. Henchcliffe is Assistant Professor of the Department of Neurology, Weill Medical College of Cornell University.

References

1. Frucht S, et al. Falling Asleep at the Wheel: Motor Vehicle Mishaps in Persons Taking Pramipexole and Ropinirole. Neurology. 1999;52:1908-1910.

2. Hobson DE, et al. Excessive Daytime Sleepiness and Sudden-Onset Sleep in Parkinson Disease. JAMA. 2002;287:455-463.