Nigrostriatal Dopaminergic System and REM Sleep Behavior Disorder
Nigrostriatal Dopaminergic System and REM Sleep Behavior Disorder
Abstract & Commentary
By Charles P. Pollak, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Pollak reports no financial relationships relevant to this field of study.
Synopsis: REM sleep behavior disorder may be an early manifestation of a more generalized neurodegenerative disorder that involves the nigrostriatal system.
Source: Kim YK, et al. The implication of nigrostriatal dopaminergic degeneration in the pathogenesis of REM sleep behavior disorder. European J Neurology doi:10.1111/j.1468-1331.2009.02854.x.
Rem sleep behavior disorder (RBD) is an intriguing disorder of older men (mainly) who enact dreams that are uniquely active and violent. Violent behavior during sleep may result from the loss of normal inhibition of motor systems during REM sleep. RBD may herald the development of neurodegenerative disorders (synucleinopathies) such as Parkinson disease (PD), multiple system atrophy (MSA), and Lewy Body dementia (DLB). The pathogenesis of RBD is therefore of particular interest.
One question concerns the role of the nigrostriatal dopaminergic system in the pathogenesis of RBD. The pharmacologic evidence is confusing. RBD readily responds to clonazepam, but that agent has no clear effects on dopamine neurotransmission. By contrast, pramipexole (Mirapex) is known to be a full D2-D4 agonist, but is ineffective in RBD associated with PD.
To clarify any role of dopamine physiology in RBD, investigators at Seoul National University in Korea subjected three groups of subjects to single-photon emission computer tomography (SPECT) after injection of [123I]FP-CIT. The groups were 14 patients with idiopathic RBD, 14 patients with PD and 12 normal controls. Group differences of [123I]FB-CIT uptake were significantly depressed for the putamen as a region of interest (ROI) and for the caudate/putamen ratio. Putamenal uptake was lowest for the PD group and intermediate for the RBD subjects. No significant correlation was observed between EMG activity during REM sleep and dopamine transporter (DAT) densities. The investigators interpret this to mean that there was no relation between DAT density and the severity of RBD. They suggest that a pathway other than the nigrostriatal dopaminergic one exists but the identity of this alternate influence on polysomnographic EMG activity is not identified.
Commentary
This is not the first time brain scanning has been used to assess dopaminergic function in RBD, but the samples reported here may be the largest to date. The findings are consistent with those of earlier studies, namely decreased striatal binding in RBD compared with healthy controls, though not PD. The observation that RBD often heralds the development of neurodegenerative disorders with parkinsonism is consistent. As is well known, RBD also accompanies established PD along with other, often severe sleep difficulties of the sleep-maintenance type. This may occur independent of any medications used to treat PD and is not simply a dopaminergic effect.
Clearly, the time is long past when PD or other neurodegenerative disorders can be managed without taking a careful sleep history and performing an overnight sleep recording to assess the EMG component for signs of disinhibition as well as the respiratory component for signs of sleep apnea.
REM sleep behavior disorder may be an early manifestation of a more generalized neurodegenerative disorder that involves the nigrostriatal system.Subscribe Now for Access
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