Assessing whole brain perfusion changes in patients with REM sleep behavior disorder S. Mazza, PhD; J.P. Soucy, MD, MSc, FRCPS(c); P. Gravel, BEng; M. Michaud, PhD; R. Postuma, MD; J. Massicotte-Marquez, BSc; A. Decary, PhD; and J. Montplaisir, MD, PhD, CRCPc Abstract—Objective: To investigate the regional cerebral perfusion in patients with idiopathic REM behavior disorder (RBD) in order to establish the topography of networks involved. Methods: We performed cerebral blood flow evaluation using 99m Tc-Ethylene Cysteinate Dimer (ECD) SPECT on eight patients with polysomnographically confirmed RBD and nine age-matched controls. Comparisons were made using SPM2. Results: We found increased perfusion in the pons and putamen bilaterally and in the right hippocampus. In addition, we observed a decreased perfusion in frontal (Brodmann area [BA] 4, 6, 10, 43, 44, 47 bilaterally and left BA 9, 46) and temporo-parietal (BA 13, 22, 43 bilaterally and left BA 7, 19, 20, 21, 39, 40, 41, 42) cortices. Conclusion: Perfusional abnormalities in patients with REM behavior disorder were located in the brainstem, striatum, and cortex. These abnormalities are consistent with the anatomic metabolic profile of Parkinson disease. NEUROLOGY 2006;67:1618–1622 REM behavior disorder (RBD) is a parasomnia char- acterized by intermittent loss of normal skeletal muscle atonia during REM sleep, and elaborate mo- tor activity associated with dream mentation. Abnor- malities observed during REM sleep result from impairment of a tonic system that controls REM atonia, and a phasic system that controls motor pat- tern generators. 1 Loss of REM sleep atonia has been attributed to loss of the inhibition of motor activity normally me- diated by pontine centers. Behavior release during REM also requires disinhibition of brainstem motor pattern generators, resulting in over-excitation of phasic motor activity. 2 These two sets of structures provide an anatomic basis for RBD. 3 Recent studies have also revealed a reduction of striatal presynaptic dopamine transporters in idio- pathic RBD. 4-6 Impaired cortical EEG activation dur- ing waking in association with cognitive impairment has also been found in idiopathic RBD. 7,8 Cumulative findings strongly suggest that RBD is more than a mere parasomnia, and could be a pro- dromal feature of neurodegenerative disorders. 9,10 Up to two-thirds of patients with RBD will eventually manifest symptoms of a neurodegenerative disorder. In many cases, RBD symptoms occur several years to decades before the onset of that subsequent dis- ease. 11 Most often, the associated disorder is one of the alpha-synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], and multi- ple system atrophy [MSA]). In this study, we investigated regional cerebral perfusion with SPECT using 99m Tc-Ethylene Cys- teinate Dimer (ECD) in untreated patients with idio- pathic RBD, to define the distribution of the networks involved. Methods. Patients and healthy control subjects. We studied eight patients (seven men and one woman; mean age  SD: 69.9  8.2 years) with idiopathic RBD confirmed by polysomnography (PSG), and nine healthy control subjects matched for sex and age (mean age  SD: 67.4  6.82 years). Patients with RBD had a mean symptom duration of 7.5  4.8 years. They showed a mean body mass index (BMI) of 26.2  2.6, similar to the BMI of con- trols (mean 26.3  5.3) (table 1). In order to rule out neurologic conditions, both patients and controls underwent a standard neurologic interview and examina- tion prior to the PSG recording. In addition, patients with sus- pected RBD were further tested for extrapyramidal dysfunction and parkinsonism by a movement disorders specialist. Subjects with probable PD or MSA were excluded. Probable PD was de- fined according to the UK brain bank criteria, as the presence of bradykinesia in association with one of the following: rigidity, rest tremor, or postural instability. 12 Subjects’ scores on the Unified PD Rating Scale (UPDRS) were recorded. 13 Subjects without any evidence of parkinsonism and an UPDRS score 10 in section III were included. Since the UPDRS was not 0 in all subjects, some RBD patients had very subtle motor signs not warranting, how- ever, a diagnosis of mild PD. Cerebral MRI was also performed for each patient and each control subject. Except for minor nonspe- cific lesions (such as single white matter lacunes or mild cortical From Centre d’E ´ tude du Sommeil et des Rythmes Biologiques (S.M., M.M., R.P., J.M.-M., A.D., J.M.), Ho ˆpital du Sacre ´-Cœur de Montre ´al; Department of Nuclear Medicine (J.P.S.), Centre Hospitalier de l’Universite ´ de Montre ´al; Department of Neurology and Neurosurgery (P.G.), McGill University, Montre ´al; and Department of Neurology (R.P.), Montreal General Hospital, Montreal, Quebec, Canada. Supported by the Canadian Institute of Health Research and The Canadian Senior Chair on Sleep Disorders. Disclosure: The authors report no conflicts of interest. Received January 12, 2006. Accepted in final form July 5, 2006. Address correspondence and reprint requests to Dr. Jacques Montplaisir, Centre d’E ´ tude du Sommeil et des Rythmes Biologiques, Ho ˆpital du Sacre ´-Cœur de Montre ´al, 5400 Boul. Gouin Ouest, Montre ´al, Que ´bec, Canada, H4J 1C5; e-mail: JY.Montplaisir@UMontreal.CA 1618 Copyright © 2006 by AAN Enterprises, Inc.