Our findings demonstrate that the frequency of probable REM sleep behavior disorder was much greater in people with Parkinson’s disease than those with restless legs syndrome, essential tremor, and controls. There is now substantial data establishing RBD as a synucleinopathy and pre-motor finding in PD, dementia with Lewy bodies, and multiple system atrophy.[2
] RBD is usually diagnosed by polysomnography, but recently, Boeve et al.[13
] have shown that with the Mayo Sleep Questionnaire pRBD can reliably be diagnosed without the sleep study. As polysomnography is time consuming and expensive, a screening questionnaire allows for investigating pRBD in larger populations.
The BSHRI cohort is predominantly volunteers from the community enrolled with the intent of donating their brains and bodies for research purposes. While patients with PD are recruited in some cases, there is no recruitment of ET or RLS cases. All subjects receive extensive annual assessments and the sleep questionnaire was added to this assessment in 2006. The findings in this study are unique as all subjects (PD, ET, RLS, and controls) were similarly assessed and there are no previous systematic studies of RLS or ET nor previous data comparing subjects with PD and controls. Given the evidence that RBD is a synucleinopathy it was of great interest to determine whether RBD is more common in ET or RLS.
Some have hypothesized that ET is a risk factor for PD and that there may be a “Lewy body variant” of ET[19
] although follow-up data was less suggestive of this hypothesis.[20
] This hypothesis has not been supported by our own work which did not find an increase in Lewy bodies in ET,[17
] nor did we find an increase in ET prevalence in a series of incidental Lewy body disease cases when compared to controls.[21
] A more detailed review of this lack of an association between ET and PD was recently published.[22
] If ET was a variant of PD, or a risk factor for developing PD, given the prevalence of ET we would have expected some increase in the occurrence of RBD in the ET group, and this was not found.
The coexistence of RLS in PD patients has been reported although whether RLS is more frequent in PD remains unclear.[23
] No data is available to show that RLS patients are at increased risk for developing PD and nor that RLS is a synucleinopathy. Our data showing that pRBD was not increased in RLS cases suggests it is unlikely to be pre-motor PD.
Excessive daytime sleepiness in PD has been well documented.[28
] Our data showing a higher overall mean for the Epworth Sleepiness Scale, and a higher percentage of cases having an abnormal score (≥10) than controls is thus confirmatory. The finding that subjects with RLS had a higher mean score and a higher percentage of cases with a score ≥10, confirms results from other recent studies.[30
] While the mean score was only minimally, but significantly elevated, the percentage of cases with a score ≥10 suggests a correlation. No evidence was found for EDS in ET, and to date there are no published reports of this.
One limitation to this study is sample size although the difference in the frequency in pRBD in PD is extremely large suggesting a clear difference between groups. A second limitation is our inability to determine whether medications may have impacted MSQ or ESS scores given the original design of the database (medications were not systematically recorded at the time the questionnaire was completed). While the use of the MSQ with a single question for RBD was used, the data presented was all from informant responses and this has previously been shown to have 98% sensitivity for RBD when validated with a sleep study.[13
] A further limitation is the paucity of longitudinal follow-up data on the subjects to determine whether ET or RLS cases with RBD are at increased risk of developing PD. As all cases are enrolled in our brain and body donation program longitudinal data is being collected and may eventually be enough for analysis. Additionally, as the number of cases with ET plus RLS is small, the possibility that subjects with both these disorders may be at increased risk for PD cannot be determined.
The lack of an association between pRBD and either ET or RLS suggests that the majority of patients with ET or RLS likely do not have a synucleinopathy. Larger numbers of cases, further longitudinal assessments, and neuropathologic examination of these cases will eventually further increase the accuracy of these results.