Combinations of Markers Provide Clues to the Underlying Neurodegenerative Disorder in REM Sleep Behavior Disorder

Abstract

Idiopathic REM sleep behavior disorder (iRBD) is a parasomnia related to REM sleep that is characterized by nocturnal behaviors in which patients appear to act out their dreams. RBD in PD occurs in 46-50% of PD patients. In about 20% of cases it occurs before the onset of classic walking motor symptoms. Several longitudinal studies have reported the natural course of iRBD. Several procedures such as positron emission tomography (PET), SPECT studies, transcranial ultrasound imaging of the substantia nigra, and cardiac MIBG scintigraphy have been proposed to identify subjects in early stage of Parkinson disease (PD) or dementia with Lewy bodies (DLB). In our study, 6-[18F]-fluorometa- tyrosine PET (FMT/PET) template superimposed onto the each individual brain MRI in PD, iRBD, and controls. Regions of interests (ROIs) for striatum and cerebellum were placed over each individual brain template. ROIs were manually drawn on the FMT/PET after overlapping with each individual brain MRI, and striatal ROI was divided into the putamen and caudate. We performed FMT-PET imaging can assess the level of presynaptic dopaminergic nerve for iRBD, PD, and controls. IRBD patients have no signs of parkinsonism and have neuroimaging evidence of almost intact striatal dopaminergic innervations such as controls. Whereas PD patients have parkinsonism by definition and have loss of striatal dopaminergic innervation, as evidenced by decreased striatal uptake. Reduced 123I-MIBG uptake by postganglionic cardiac sympathetic neurons in patients with early stage PD has made this technique a useful early marker of this disease. We determined that these same 123I-MIBG findings were present in patients with iRBD. H/M ratio was significantly lower in RBD, PD and DLB subjects compared to essential tremor and multiple system atrophy (MSA) and PSP. It has been speculated that iRBD might represent a prodromal form of neurodegenerative diseases referred to as synucleinopathies such as PD, MSA, and DLB.