Many people with REM sleep behavior disorder (RBD), a disease associated with disturbance of sleep, eventually develop Parkinson’s disease. Dysfunction and degeneration of specific regions of the brain stem is thought to cause RBD. Degeneration of the same regions of the brain stem is also thought to contribute to postural instability and gait disturbances, such as freezing of gait (FOG), in a subset of people with PD. This project will examine the general hypothesis that RBD and PD with FOG share a common underlying cause.
Brain imaging, sleep and gait studies will be conducted to compare and contrast four groups of subjects: people with RBD alone; people with PD who have severe FOG problems; people with PD who do not have FOG, and control subjects. Diffusion tensor imaging (DTI) will be used to examine the integrity of specific regions of the brain (pedunculopontine nucleus, locus coeruleus, and substantia nigra), overnight sleep studies will be used to assess the presence of RBD, and the gait initiation and continuation tasks will be tested in a gait laboratory.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Currently, the mechanisms contributing to, or predicting, the progression of PD to a form that is dominated by postural instability and gait disturbances are poorly understood. This project will examine the relationship between RBD and PD with FOG. If it is shown that RBD and PD with FOG share common abnormalities in brain stem structure and gait, these findings will provide initial evidence that the presence of RBD predicts the presence and progression to PD with FOG. These findings could ultimately lead to the development of early screening tests and therapeutic interventions.
We anticipate that the results of this study will provide insight into the commonalities of brain stem degeneration and gait impairment between people with PD who have FOG and people with RBD. Similarly, we expect to be able to differentiate between people with PD who present with and without FOG based on differences in brain stem imaging and gait performance. The results of this study will provide a rationale for longitudinal studies examining the progression of RBD to PD with FOG.
As of January 19, 2011, we have conducted 28 experiments across 8 subjects. Six subjects have completed all four data collection components of the study: an initial screening exam, a brain imaging study (diffusion tensor imaging) study, an overnight sleep study (polysomnography), and a laboratory experiment to assess and quantify their preparation and initiation of walking and walking and turning abilities. We have developed brain imaging methods that allow us to compare the integrity of three brain stem structures (pedunculopontine nucleus, locus coeruleus, and substantia nigra) across groups. These measures will be used to examine the relationship between changes in brain structure and the presence of sleep and gait disturbances. The results of this study will provide initial insight into the commonalities of brain stem degeneration and gait impairment between people with PD who have freezing and people with RBD.
As of February 15, 2012 we will have conducted a total of 97 experiments (sleep, gait and MRI) across 34 subjects (goal = 40 subjects, 10/group). Preliminary analysis of the gait initiation data shows that the magnitude and timing of forces associated with step initiation were reduced in patients with- (PD+FOG) and without- (PD-FOG) freezing of gait compared to matched control and idiopathic REM sleep behavior disorder (iRBD) subjects. However, the iRBD group showed an abnormal pattern of fractionated muscle activity that resembled the pattern observed in the PD groups. Sleep studies showed significant abnormalities in REM sleep-related muscle activity in both the iRBD and PD+FOG groups compared to control subjects. Preliminary MRI findings show a reduction in fractional anisotropy in the posterior region of the substantia nigra (SN) in the PD-FOG group, but not the PD+FOG or iRBD groups. The iRBD group was differentiated from the PD and control groups by reductions in FA values in the region of the anterior SN and PPN. Both PD groups and the iRBD group showed changes in inferior regions of the locus coeruleus. These preliminary data provide initial evidence that there are distinct structural and functional commonalities and differences in the pathophysiology of iRBD and PD+FOG, and between PD+FOG and PD-FOG.
Presentations & Publications
L. Alibiglou, C. Marlin, A. Videnovic, P.J. Planetta, D.E. Vailancourt, and C.D. MacKinnon. (2012). Gait initiation in REM sleep behavior disorder and Parkinson's disease with freezing of gait. 16th Annual Congress of Parkinson’s Disease and Movement Disorders. Dublin, Ireland, June 2012.
A.Videnovic, C. Marlin, L. Alibiglou, P.J. Planetta, D.E. Vaillancourt, and C.D. MacKinnon. (2012). REM sleep without atonia and freezing of gait in Parkinson’s disease. 16th Annual Congress of Parkinson’s Disease and Movement Disorders. Dublin, Ireland, June 2012.