24 Sep 2010

Having nightmares is bad enough, but some people actually act out their dreams while asleep, a syndrome known as rapid eye movement (REM) sleep behavior disorder (RBD). Diving out of bed to make a winning “catch” in a dream football game may seem innocuous to some, but recent work has solidified connections between RBD and diagnosis of Parkinson disease and other synucleinopathies decades later (Claassen et al., 2010). A more recent report published online September 15 in The Lancet Neurology suggests that neuroimaging could help pinpoint which RBD patients may develop dementia soonest. Using brain scans on people with the syndrome, scientists in Europe found PD-like changes lurking within the substantia nigra of those who were cognitively normal but went on to develop PD or a related disorder within 2.5 years. The findings suggest it may be possible to identify people with high short-term risk of PD or related disorders. “This would be of great importance when neuroprotective strategies become available,” lead researcher Alex Iranzo of the Hospital Clinic of Barcelona, Spain, told ARF via e-mail.

In both retrospective (Iranzo et al., 2006) and prospective (Postuma et al., 2009) analyses, researchers have found that about half of RBD patients develop PD or another synucleinopathy within a decade or so. However, not nearly everyone with RBD has an evolving neurodegenerative disorder, said Bradley Boeve of Mayo Clinic, Rochester, Minnesota, in an interview with ARF. Furthermore, the interval between an initial report of sleep problems and first signs of cognitive decline can vary considerably—from 15 to 50 years in Boeve’s recent retrospective of long-duration RBD (Claassen et al., 2010 and ARF related news story). So what is a clinician to tell someone with RBD?

Aiming to narrow down who may truly be on the verge of developing PD or other synucleinopathies, Iranzo and colleagues put two brain imaging tools to the test in a longitudinal study of 43 people with diagnosed RBD. In one method, single photon emission computed tomography (SPECT) imaging uses a 123I-radiolabeled ligand to measure levels of dopamine transporter (DAT), which are typically reduced in the substantia nigra of PD patients due to steep cell loss in this brain area. In addition, the researchers looked for brain abnormalities in the RBD patients using an ultrasound method that detects regions with increased iron deposition, which has been suggested to be involved in PD (Walter et al., 2010). The trouble spots in the substantia nigra bounce echo unusually well and show up on the sonogram as “hyperechogenicities.”

Iranzo and colleagues found that they were correct to suspect that these neuroimaging changes typical of early PD would also show up in people with the sleep disorder. When assessed 2.5 years after brain imaging, 27 of the 43 RBD patients had either reduced striatal dopamine activity, midbrain hyperechogenicity, or both. Among these 27 with PD-like brain changes, eight developed a synucleinopathy after 2.5 years follow-up. Five had PD, two had dementia with Lewy bodies, and one had multiple system atrophy. Of the 15 participants who looked normal by both brain imaging tools, none developed a neurological syndrome during follow-up.

An obvious question is whether those who had something amiss in their neuroimaging, but remained neurologically sound during this study, will eventually show signs of PD or the other disorders. Continued clinical follow-up of these patients should help address this issue, Iranzo said.

The current work adds to a growing body of literature supporting the use of DAT imaging for clinical as well as research purposes, Boeve told ARF. The technique is approved in Europe, and used mainly on patients who have atypical PD symptoms and/or lack cardinal clinical features, though also sometimes for routine diagnosis. In the U.S., though, DAT imaging has not even entered the research arena. The Peripheral and Central Nervous System Drugs advisory committee of the U.S. Food and Drug Administration (FDA) has voted to recommend DAT imaging to the FDA, and the FDA decision is pending. Many clinicians and researchers in the U.S. are planning to use DAT imaging once approved.”

To date, the ultrasound method has been used in Europe as well, Boeve noted, with comparatively few U.S. studies featuring the technique.

The current work “underscores the usefulness of studying adequate numbers of patients longitudinally with a spectrum of clinical tests and potential biomarkers to assess the natural history of RBD and prepare for future clinical trials,” Boeve wrote in an accompanying editorial.—Esther Landhuis

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References

News Citations

1. Paralysis Lost: Acting-Out Dreams Precede Parkinson’s Dementia 6 Aug 2010

Paper Citations

1. Claassen DO, Josephs KA, Ahlskog JE, Silber MH, Tippmann-Peikert M, Boeve BF. REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. 2010 Aug 10;75(6):494-9. PubMed.
2. Iranzo A, Molinuevo JL, Santamaría J, Serradell M, Martí MJ, Valldeoriola F, Tolosa E. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006 Jul;5(7):572-7. PubMed.
3. Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology. 2009 Apr 14;72(15):1296-300. PubMed.
4. Walter U, Skoloudík D, Berg D. Transcranial sonography findings related to non-motor features of Parkinson's disease. J Neurol Sci. 2010 Feb 15;289(1-2):123-7. PubMed.

External Citations

1. accompanying editorial

Further Reading

Papers

1. Claassen DO, Josephs KA, Ahlskog JE, Silber MH, Tippmann-Peikert M, Boeve BF. REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. 2010 Aug 10;75(6):494-9. PubMed.
2. Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology. 2009 Apr 14;72(15):1296-300. PubMed.
3. Iranzo A, Molinuevo JL, Santamaría J, Serradell M, Martí MJ, Valldeoriola F, Tolosa E. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006 Jul;5(7):572-7. PubMed.

News

1. Paralysis Lost: Acting-Out Dreams Precede Parkinson’s Dementia 6 Aug 2010