Table.

Features/Symptoms, Associated Clinical and Ancillary Test Findings, and Their Interpretation in Patients with “Idiopathic” REM Sleep Behavior Disorder

Clinical Feature or Symptom	Findings Detectable on Measurement Techniques/Biomarkers	Interpretation
Dysnosmia/anosmia	Smell testing – impaired odor identification and discrimination	Degeneration of olfactory structures (begin in Stage 1)
Orthostatic hypotension Constipation Erectile dysfunction Urinary incontinence Decreased sweating	Peripheral and central autonomic function testing Cardiac MIBG imaging – reduced cardiac sympathetic activity	Degeneration of structures in the brainstem, intermediolateral cell column, and peripheral ganglia involved in autonomic functioning (? begin in Stage 1)
REM sleep behavior disorder	Polysomnography – degree of REM sleep without atonia	Degeneration of the brainstem structures (sublaterodorsal nucleus, precoeruleus, and magnocellular reticular formation) involved in REM sleep circuitry (begins in Stage 2)
Depression	Various measures for assessing mood	Degeneration of raphe nucleus and/or locus coeruleus (begins in Stage 2)
Apathy	Various measures for assessing apathy	? degeneration of raphe nucleus and/or locus coeruleus (begins in Stage 2)
Anxiety	Various measures for assessing apathy	? degeneration of raphe nucleus and/or locus coeruleus (begins in Stage 2)
Sleep fragmentation with insomnia	Polysomnography – frequent arousals for no apparent reason	? degeneration of raphe nucleus, locus coeruleus, sublaterodorsal nucleus, precoeruleus, pedunculopontine nucleus, laterodorsal nucleus, tuberomamillary nucleus (begins in Stage 2/3)
Hypersomnia	Epworth Sleepiness Scale – increased tendency to doze Multiple Sleep Latency Test or Maintenance of Wakefulness Test – reduced initial sleep latency	? degeneration of brainstem nuclei (begins in Stage 2/3) Degeneration of hypocretin-1 cells in the lateral hypothalamus (begins in Stage 3)
Parkinsonism	Timed up and go Gait testing – increased variability in gait measures Clinical examination/Unified Parkinson’s Disease Rating Scale – rest tremor, bradykinesia, rigidity, postural instability, reduced armswing, masked facies Dopamine transporter scan (DaTscan) – reduced striatonigral uptake of dopamine transporter on SPECT imaging Fluorodopa positron emission tomography (FD-PET) – reduced fluorodopa metabolism in nigrostriatal system Transcranial ultrasonography (TCS) – midbrain echogeneity	Degeneration of substantia nigra (begins in Stage 3)
Cognitive impairment	Neuropsychological testing – impairment in one or more cognitive domains	Degeneration of the cholinergic basal forebrain and limbic/neocortical structures and their efferent/afferent connections (begins in Stage 4)
Color vision	Farnsworth-Munsell-100-Hue test (FM-100) – impaired color vision testing	Degeneration of retinal and/or visual cortex structures (begins in Stage 6)
Asymptomatic – electrophysiologic and imaging measures	Electroencephalography (EEG) – diffuse slowing, increased theta/delta power Magnetic resonance spectroscopy (MRS) – altered metabolic ratios in key regions of interest Magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) – altered fractional inosotropy and mean diffusivity in key brain regions MRI voxel based morphometry (VBM) – altered gray matter density of hippocampus MRI based corticometery – decreased neocortical thickness in frontal and/or parietal regions Brain single photon emission computed tomorgraphy (SPECT) – hypoperfusion of cortical structures, particularly occipital region Fluorodeoxyglucose positron emission tomography (FDG-PET) – hypometabolism of cerebral cortex, particularly occipital region	Degeneration of various brain structures (begins in Stages 2–4)