Subclinical REM Sleep Behavior Disorder and Its Clinical and Research Implications

The recent report by Miyamoto et al.1 on comparably reduced cardiac 123I-MIBG accumulation in idiopathic REM sleep behavior disorder (iRBD), Parkinson's disease (PD), and Dementia with Lewy bodies, which implicates parkinsonian pathology (Lewy bodies; α-synuclein) in cardiac postganglionic sympathetic and intrinsic neurons, contains the following comment on the 31 iRBD patients (mean age, 66 yrs; 23 males): “In most cases, a marked reduction in 123I-MIBG accumulation occurred soon after the onset of the disease.” Therefore, most iRBD patients presumably had cardiac neuronal parkinsonian pathology present around the time that their RBD emerged. This finding can be considered together with findings from a SPECT brain imaging study of iRBD and subclinical iRBD by Eisensehr et al.2 in which decreased striatal presynaptic dopamine transporters correlated negatively with increased electromyographic (EMG) muscle activity during REM sleep. In that study, significant differences in striatal presynaptic dopamine transporters were found across a gradient in 4 groups: PD patients, iRBD patients, subclinical iRBD patients (i.e., those with increased EMG activity in REM sleep without clinical RBD behaviors), and normal controls.2 The 8 subclinical iRBD patients (mean age, 62 years; 6 males) had a significant decrease of striatal presynaptic dopamine transporters compared to normal controls. These findings in a small sample, though not yet replicated, represent an objective marker of presumed parkinsonian involvement in subclinical iRBD, which carries clinical and research implications, particularly since most middle aged and older patients with iRBD will eventually develop a parkinsonian disorder. 3,4 PSG scoring criteria for identifying subclinical RBD exist, which utilize a threshold value of 15%–20% of REM sleep with increased EMG muscle activity.2,5 Subclinical RBD includes either PSG abnormalities alone or with non-clinical behaviors in REM sleep, such as limb twitching and jerking, and simple behaviors. Since subclinical RBD is usually an incidental finding during a clinical PSG study, sleep clinicians who review and interpret PSG studies should be aware that subclinical RBD may carry a risk not only for future clinical RBD but also for parkinsonism in middle-aged and older patients. Therefore, we recommend that patients with subclinical RBD undergo a neurologic history and exam, and have their primary care physicians be informed about the possible implications associated with age-related subclinical RBD, with the caveat that medication-induced cases may not carry a parkinsonian risk.3 The longitudinal course of subclinical RBD is unknown. Subclinical RBD (also called preclinical RBD, and REM sleep without atonia [RWA]) may remain asymptomatic or resolve partially or completely, or it could progress to i) clinical iRBD; ii) clinical iRBD with progression to PD/other parkinsonism; or iii) PD/other parkinsonism directly without any clinical RBD. The RBD and parkinsonian implications are currently not known for subclinical RBD associated with younger age groups, and also for all age groups with subclinical RBD associated with medications, alcohol and drug abuse, narcolepsy, and other neurologic disorders. A growing number of non-motor abnormalities found in PD are also found in iRBD, besides the two mentioned above, including olfactory dysfunction, visuospatial constructional dysfunction and visuospatial memory impairment, etc.4 Middle-aged and older adults with subclinical iRBD may be suitable candidates for research studies probing for the non-motor abnormalities already found in iRBD and PD. Results of such studies may indicate that a future clinical research goal already recognized for iRBD also pertains to subclinical iRBD (in middle-aged and older adults), viz. to enroll patients in studies utilizing neuro-protective agents that would retard or prevent progression to future parkinsonism.3 As yet, no effective neuroprotective agent has been found, however.