The articles listed on this page are from a variety of sources. 
1. The staff of DBS-STN often attends conferences or educational opportunities both nationally and internationally, and a brief understandable write-up of the information presented at the event will be provided for our readers to review. 
2. DBS-STN staff also identifies or writes various articles related to topics that are thought to be of interest for the reader of www.DBS-STN.org. 

Browse by Topic:
Search:

The 9th International Congress of Parkinson's Disease and Movement Disorders - Part Two: Sleep Disorders in Parkinson's Disease

The Parkinson Alliance/DBS-STN Research Team

The summary to follow includes information presented by David Rye, M.D., Ph.D. from the Department of Neurology at Emory University in Atlanta, Georgia, Cynthia Comella, M.D. from the Department of Neurology at Rush University Medical Center in Chicago, Illinois, Brad Boeve, M.D. from the Mayo Clinic's Sleep Disorders Center in Rochester, Minneapolis, and Claudia Trenkwalder, MD from Paracelsus-Elena-Klinik in Kassel, Germany. Additionally, some information that was included in some of the poster sessions is cited.

Between 60 and 98% of people with Parkinson's disease (PD) experience sleep-related disturbances (Partinen, 1997; Tandberg, 1998). For individuals with PD, the most common forms of sleep disturbances include nocturnal sleep disruption and excessive daytime sleepiness, restless legs syndrome, rapid eye movement sleep behavior disorder, sleep apnea, nightmares, sleep terrors, and panic attacks. Sleep/wake abnormalities are common in the elderly, but are more common and more severe in those with PD. The majority of patients with Parkinson's disease complain of nocturnal sleep disturbances and about 15% report excessive daytime sleepiness (EDS). The sleep disturbances discussed at the conference included insomnia, narcolepsy, excessive daytime sleepiness, and rapid eye movement sleep behavior disorder.

Insomnia:

Insomnia can be described as having difficulty initiating and/or maintaining sleep. Moreover, difficulty falling asleep, staying asleep and waking earlier than desired are all symptoms of insomnia. Anti-parkinsonian drugs also play a role in insomnia by increasing daytime sleepiness and affecting motor symptoms and depression. Although insomnia can occur for a number of reasons, such as stress, depression, and pain, most commonly, sleep may be disrupted at night due to the movement disturbances caused by PD. Furthermore, the loss of the medication effect during the night can lead to feeling uncomfortable in bed, restlessness, and/or periodic limb movements.

Dr. Brad Boeve from Mayo Sleep Disorders Center addressed the importance of understanding the impact of medications on sleep disturbances. For example, he indicated that carbidopa/levadopa can cause insomnia. Additionally, antidepressants, such as Prozac, Wellbutrin, and Effexor have activating properties that may cause individuals to have sleeping difficulties. Further descriptions of pharmacologic effects on sleep are addressed in the section entitled "Treatment" that follows.

Narcolepsy:

Narcolepsy is a medical condition that makes individuals go to sleep suddenly and unexpectedly. Narcolepsy is characterized by episodes of frequent, uncontrollable daytime sleeping, usually preceded by drowsiness. The episodes usually occur after meals, but sudden onset of sleep may occur while working or driving a vehicle, having a conversation, or being in any sedentary or non-stimulating situation. During a narcoleptic moment, there is a brief period of sleep, and the person awakens feeling refreshed. However, the person may again become uncontrollably sleepy a short time later.

Narcolepsy can also be associated with cataplexy, which is a brief episode of severe loss of tone of various muscles. Generalized weakness may occur for a few moments during the transition between sleep and wake (sleep-paralysis). Many people with narcolepsy also have dreamlike hallucinations in the transition between sleep and wakefulness.

The exact cause of narcolepsy is unknown. Studies have indicated that the disorder may be genetic, with studies showing gene markers that may indicate a tendency to develop narcolepsy (Rissling et al, 2004; Wieczorek et al., 2004). A small group of neurons in the brain has been implicated in producing transitions from sleep to wakefulness and vice-versa, and people with narcolepsy may have fewer of these neurons or the neurons may have been damaged. It is believed that the diminished neurotransmitters (chemicals in the brain) involved in PD may have an effect on the increased experience of narcolepsy.

Excessive Daytime Sleepiness:

Excessive daytime sleepiness (ESD), which has also been referred to as "sleep attacks," is reported to occur in approximately 40% of patients with PD (Aldrich, 1994). Others have found the prevalence to occur between 16% (Tanbeg et al., 1999) and 57% (Ondo, 2002; Comella, 2002). Furthermore, Dr. Cynthia Comella highlighted the point that in earlier stages of PD, individuals may not have any symptomatic sleep disturbances; however, in the later stages of PD, 60 to 90% of individuals may experience sleep disturbance. To support her point, she cited Gjserstad and colleagues (2002) who found that the development of EDS correlated with more advanced disease. In other words, the longer the disease duration, the greater the likelihood that a patient with PD will experience EDS.

Although EDS has been thought to be an under-recognized condition, it has been studied in greater depths in recent years, as the prevalence and the impact of EDS in patients with PD continue to become more pronounced. With regard to the latter, EDS often presents a considerable burden to patients and caregivers, limiting social interactions, creating potentially dangerous situations, and influencing tolerance to anti-Parkinson medications.

Dr. Cynthia Comella provided an excellent presentation that led to a better understanding about the potential causes of EDS. In sum, she stated, EDS in patients with PD can be due to three factors: 1. PD related nocturnal sleep deprivation (as noted in the aforementioned section "insomnia"), 2. medications, and/or 3. changes of the brain secondary to the disease process (as noted in the aforementioned section "narcolepsy"). With regard to the medications, there continues to be controversy as to whether or not medications induce sleep attacks. For example, controversial reports of sudden onset 'sleep attacks' resulting in road traffic accidents have recently been reported in patients with PD taking certain medications, such as Pramipexole and Ropinirole (Chaudhuri et al., 2002; Frucht, et al. 1999). These reports have generated considerable debate as the concept of EDS is disputed amongst sleep specialists, and most believe that isolated 'sleep attacks' not preceded by warning on the background of chronic sleepiness or 'unintended sleepiness' do not exist. During Dr. Comella's presentation, there was notation of a series of case reports suggesting that EDS is very likely influenced by medications, at least in part. Further, the phenomenon may not be exclusive to Pramipexole or Ropinirole and indeed may occur with most medications with dopaminergic agents (chemicals within medications to treat Parkinson's disease ( e.g., Levodopa). Once again, there is also recent evidence suggests that sleepiness in reaction to dopaminergic therapy may be related to underlying dopamine deficiency of PD rather than a drug effect. The take home message is that EDS is recognized and further investigations need to be conducted to discern the cause of EDS.

Rapid Eye Movement Sleep Behavior Disorder (RBD):

Rapid Eye Movement Sleep Behavior Disorder (RBD) was discussed at great length during this conference. RBD is a sleep disturbance that is not uncommon in patients with Parkinson's disease. It is characterized by aggressive nocturnal behavior during rapid eye movement (REM) sleep. Although the clinicians who treat PD patients are hearing about RBD in greater frequency, the prevalence of RBD in this population remains poorly defined. At this point, the scientific literature has reported that the occurrence of RBD in Parkinson's disease varies from 15 to 47%. Interestingly and of note, sometimes RBD has been reported to precede the onset of parkinsonism (e.g., motor disturbances).

Dr. Claudia M Trenkwalder provided multiple videos illustrating the violent and disruptive behavior during REM sleep. She noted that the movements during this sleep disturbance tend to be related to the dream content. Specifically, she indicated that many PD patients will laugh out loud if they are dreaming about something comical, or they may scream and swing their arms if they are feeling threatened in their dreams. She also reported that RBD may be an early indicator of PD, but future research is needed to prove this hypothesis.

A research project that was presented at this conference assessed dream content and gender in REM sleep behavior disorder in Parkinson's disease (Borek et al., 2005). The objective was to determine whether dream content differs between males and females with RBD and between those with RBD and those without RBD in patients with idiopathic Parkinson's disease (PD). A secondary aim was to evaluate whether RBD is associated with depression and anxiety. The results of the study found that dream content of males with RBD was violent and included being chased, attacked by people and animals, and fighting the aggressor. Dream content of females was nonviolent and involved being chased but did not include physical confrontation. The majority of patients without RBD had dreams that involved feelings of loneliness and loss of control. RBD was found to be more common in males and the frequency of RBD increased as the duration of PD increased. Additionally, depression, anxiety, and duration of PD were significantly related to poor sleep quality and nightmare distress. Furthermore, those who reported nightmares also reported increased daytime somnolence.

Simuni and colleagues (2005) conducted a study on the prevalence of rapid eye movement behavior disorder (RBD). Specifically, their study involved a retrospective study based on the review of clinical records and polysomnography (the process of monitoring and recording physiologic (brain wave) data during sleep). Their objective was to establish prevalence of RBD in patients referred to a large tertiary sleep disorders center, to establish prevalence of parkinsonism in patients with RBD, and to evaluate co-morbidity of RBD with other sleep disorders. A total of 6, 436 records were reviewed for this study. Thirty-three subjects with a clinical diagnosis of probable RBD were identified. Three of the thirty-three people reviewed carried a diagnosis of parkinsonism. The investigators concluded that the prevalence of RBD in their cohort was .36%. These investigators believe that clinical diagnosis of probable RBD overestimates the prevalence of this disorder. Additionally, prevalence of parkinsonism in their cohort was much lower than reported in the literature. They indicated that this finding likely reflects the limitations of retrospective sleep records based data collection.

Treatment:

When a patient or a family member begins to notice sleep disruption, an evaluation by a specialist is very important. Moreover, treatment for sleep disturbance may not only increase one's physical activity, social activity, and safety while operating a motor vehicle, but it will also improve one's quality of life. Dr. Boeve indicated that a thorough assessment should include complete medical and psychiatric histories, sleep history, and a 1- to 2-week sleep diary or Epworth Sleepiness Scale evaluation (a scale that helps to assess sleep disturbance). Polysomnography or actigraphy (actigraphy provides a means for clinicians and researchers to measure sleep quality by using an instrument that records motor activity) may also be indicated. Furthermore, treatment should address underlying factors such as possible depression, anxiety or pain.

It is also important to be knowledgeable about the impact that medications may be having on sleeping habits. In some cases, medications have been found to increase somnolence (e.g., Pramipexole; Ropinirole). In other cases, medications have been found to be very helpful in the treatment of sleep disturbance. For example, in the treatment of Rapid Eye Movement Sleep Behavior Disorder (RBD), Clonazepam has been found to be quite effective in treating RBD in PD patients (Schenck et al., 1993). Melatonin has also been found to be helpful for insomnia (Dowling et al., 2003). Medications such as Remeron, Paxil, and Amitriptyline may also be helpful in treating insomnia, but some of these medications may have side effects that can cause confusion. Pharmacological treatment for "arousal for no apparent reason" (AFNARs) includes Trazadone, Chloral Hydrate, and Zolipedem (medications to help individuals sleep). For daytime sleepiness, psychostimulants (e.g., Ritalin) have been found to be helpful. Furthermore, phototherapy (also known as light therapy) has been shown to help individuals with PD. For example, in individuals with some sleep syndromes, phototherapy in the mid to late afternoon for 45 minutes to 1 hour can help improve both mood and sleep quality.
Of note, some medications such as Selective Serotonin Reuptake Inhibitors (SSRIs) can exacerbate sleep disturbances (e.g., RBD). In other cases, some medications have activating effects, and consuming the medications at specific times of the day is recommended. For example, Aricept and Reminyl (often prescribed to benefit memory and thinking) should be taken earlier in the day, as taking them in the evening may cause individuals to have trouble falling to sleep at night. In conclusion, it is important to talk to a doctor about any sleep disruption and inquire as to the effects that some of the medications may be having on your sleep.

 

References

Aldrich M., (1994). Parkinsonism. In: Kryger MH, Roth T, Dement WC, eds. Principles and practice of sleep medicine. Philadelphia: WB Saunders Co, 783789.

Borek, L., Kohn, R., & Freidman, J. (2005). Dream content and gender in REM sleep behavior disorder in Parkinson's disease: Preliminary findings. Presented at the 9th International Congress of Parkinson's Disease & Movement Disorders, New Orleans.

Overeem, S.C. Steens, C.D. Good et al., Voxel-based morphometry in hypocretin-deficient narcolepsy. Sleep 26 (2003), pp. 44 & 46.

C. Kaufmann, A. Schuld, T. Pollmacher et al., Reduced cortical gray matter in narcolepsy: preliminary findings with voxel-based morphometry. Neurology 58 (2002), pp. 1852 &1855.
Chaudhuri, K. R., S. Pal, et al. (2002). 'Sleep attacks' or 'unintended sleep episodes' occur with dopamine agonists: is this a class effect?" Drug Safety, 25(7): 473-83.

Dowling, G., Mastick, J., & Aminoff, M. (2003). Melatonin Treatment for Insomnia in Parkinson's disease: A pilot study. Sleep Research Online, 5(3), 99-103).

Frucht S, Rogers JD, Greene PE, Gordon MF, & Fahn S. (1999). Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology, 52(9):1908-1910.

Gjerstad M.D, Aarsland D., & Larsen J.P. (2002). Development of daytime somnolence over time in Parkinson's disease. Neurology, 58 (10), 1544-1546.
Partinen, M. (1997). Sleep disorder related to Parkinson's disease. Adv. In Neurology, 40, 271-277.

Rissling, I., Geller, F., Bandmann, O., Stiasny-Kolster, K., Korner, Y., Meindorfner, C., Kruger, H.P., Oertel, W.H., & Moller, J.C. (2004). Dopamine receptor gene polymorphisms in Parkinson's disease patients reporting "sleep attacks". Movement Disorders, 19(11), 1279-1284.

Schenck C.H., Hurwitz T.D., & Mahowald, M.W. (1993). Symposium: Normal and abnormal REM sleep regulation: REM sleep behaviour disorder: an update on a series of 96 patients and a review of the world literature. J. Sleep Res. 2(4), 224-231.

Tandberg, E., Larsen, J.P., & Karlsen, K.A. (1998). A community-based study of sleep disorders in patients with Parkinson's disease. Movement Disorders, 13, 895-899.

Wieczorek, S., Jagiello, P., Arning, L., Dahmen, N., & Epplen, J.T. (2004). Screening for candidate gene regions in narcolepsy using a microsatellite based approach and pooled DNA. Journal of Molecular Medicine, 82(10), 696-705.



Article Archive

back