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What's Hot in PD? Is light therapy a potential treatment modality in Parkinson’s disease?

Recent research has indicated that there may be unexplored symptomatic benefits by using light therapy to treat Parkinson’s disease patients. This “light” approach is particularly appealing in Parkinson’s disease because patients commonly suffer from excessive daytime sleepiness A chronic condition characterized by difficulty staying awake or paying attention; may be due to underlying sleep disorders, depression or some medications., fatigue, sleep disorders, as well as depression A mood disorder whose symptoms can include a persistent sad or empty mood, feelings of hopelessness or pessimism, irritability and loss of interest or pleasure in previously enjoyable activities.—and all have been reported to potentially improve. In this month’s What’s Hot Column, we explore the scientific underpinnings of the brain’s natural sleep-wake cycle; called the circadian rhythm. The scientific term circadian rhythm is derived from the Latin words circa which means approximately, and diem which means day. The human sleep wake cycle has this been referred to as a circadian rhythm as it occurs everyday. Melatonin A hormone made in the pineal gland that is tied to the sleep-wake cycle; levels rise toward the end of the day, signaling nighttime, and drop in the early morning, causing you to wake up. has been heavily implicated in the human sleep-wake cycle, and we will review both melantonin and light therapy, as potential symptomatic approaches for Parkinson’s disease.

Many investigators have focused on melatonin as an important chemical in the human sleep-wake circadian rhythm. Melatonin is manufactured in the center of the brain in a structure called the pineal gland. René Descartes referred to the pineal gland as the “seat of the soul.” Melatonin from the pineal gland can trigger sleepiness, and can also lower body temperature. The manufacture of melantonin is disrupted by exposure to light. Researchers have postulated that by intervening in the melatonin pathways by exposing people to bright light could have a therapeutic benefit.

Videnovic and colleagues at the Parkinson's Foundation Center of Excellence in Northwestern University recently explored blood melatonin tests sampled over 24 hours. The tests were designed to uncover some of the mysteries of fatigue, and the sleep-wake disturbances in Parkinson’s disease. The researchers studied twenty Parkinson’s patients and twenty control patients without Parkinson’s. Melatonin blood levels were checked every thirty minutes for twenty-four straight hours. Parkinson’s patients were observed not to secrete melatonin in a normal pattern. Parkinson’s disease patients in the study who suffered from excessive daytime sleepiness or fatigue had more dysfunction in the patterns of melatonin than those without excessive daytime sleepiness or fatigue. How long you had Parkinson’s disease, how severe your motor symptoms were, and what medications you were taking, were not related to the circadian rhythm. The author’s postulated that sleep-wake circadian function could be improved by timed exposure to bright light, and also potentially by exercise. There have been several other small studies that have also suggested Parkinson’s disease motor, as well as non-motor symptoms, may improve with light therapy.

In May 2014, at the 66th Annual Meeting of the American Academy of Neurology (AAN), Videnovic and colleagues presented another study on the preliminary results of light therapy for excessive daytime sleepiness or fatigue. There were thirty patients included with an average duration of disease of approximately seven years. The study intervention was bright light therapy (5000 lux) or dim red-light therapy (300 lux) delivered for two hours a day for fourteen days. The results did not reveal a difference between the groups, however a closer look at the scores in this small study revealed that the Epworth Excessive Sleepiness Scale improved by 2.3 points in the dim red light group, and 4.3 points in the bright light therapy group. Though these results were not robust, they suggested, at least the possibility, that light therapy could be optimized for better results in Parkinson’s disease. Some researchers have suggested that better penetrance of light therapy could be delivered through other techniques including deep brain electrodes, but this remains highly investigational and has only been attempted in animals.

If melatonin release is blocked by exposure to light, and exposing patients to light may improve Parkinson’s disease symptoms, why would patients intentionally take melatonin? Melatonin (N-acetyl-5-methoxy-tryptamine) is also an antioxidant. Neurodegenerative disorders such as Parkinson’s disease have been linked to oxidative damage and free radical generation, and some people believe that melatonin may help in blocking neurodegeneration. There are however no human studies to support the notion that melatonin slows or blocks neurodegeneration. Some patients also use melatonin for sleep issues, though again there are no large well-controlled studies to support this notion, and in many cases reports have surfaced that melatonin replacement may actually worsen sleep in Parkinson’s disease. I have personally listened to several patients who have tried melatonin, and reported worsening in sleep. If you decide to try melatonin (which is over the counter) for sleep, you should do it under the guidance of a physician. Until more data is published, we cannot make a recommendation as to the usefulness of melatonin replacement for sleep issues.

The bottom line is that there is accumulating evidence that melatonin is important to sleep and to excessive daytime sleepiness in Parkinson’s disease. Melatonin can possibly be powerfully modulated by light therapy and also possibly by exercise. Melatonin pills may not be the answer for many patients with Parkinson’s disease and could potentially worsen symptoms. More research will be needed to clarify how shining a light on Parkinson’s disease may provide a new option for patients, especially those with excessive daytime sleepiness.

Selected References

Videnovic A, Noble C, Reid KJ, Peng J, Turek FW, Marconi A, Rademaker AW, Simuni T, Zadikoff C, Zee PC. Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease. JAMA Neurol. 2014 Apr;71(4):463-9. doi: 10.1001/jamaneurol.2013.6239. PubMed PMID: 24566763.

Bolitho SJ, Naismith SL, Rajaratnam SM, Grunstein RR, Hodges JR, Terpening Z, Rogers N, Lewis SJ. Disturbances in melatonin secretion and circadian sleep-wake regulation in Parkinson disease. Sleep Med. 2014 Mar;15(3):342-7. doi: 10.1016/j.sleep.2013.10.016. Epub 2014 Jan 21. PubMed PMID: 24529544.

Cardinali DP, Pagano ES, Scacchi Bernasconi PA, Reynoso R, Scacchi P. Melatonin and mitochondrial dysfunction in the central nervous system. Horm Behav. 2013 Feb;63(2):322-30. doi: 10.1016/j.yhbeh.2012.02.020. Epub 2012 Feb 25. Review. PubMed PMID: 22391273.

Ortiz GG, Benítez-King GA, Rosales-Corral SA, Pacheco-Moisés FP,Velázquez-Brizuela IE. Cellular and biochemical actions of melatonin which protect against free radicals: role in neurodegenerative disorders. Curr Neuropharmacol. 2008 Sep;6(3):203-14. doi: 10.2174/157015908785777201. PubMed PMID: 19506721; PubMed Central PMCID: PMC2687933.


You can find out more about our National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease.

What's Hot in PD?
Mon, 06/02/2014
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