Clinical and dopaminergic imaging characteristics of the FARPRESTO cohort of trial-ready idiopathic rapid eye movement sleep behavior patients

Introduction: Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is considered the prodromal stage of alpha-synucleinopathies. Thus, iRBD patients are the ideal target for disease-modifying therapy. The risk FActoRs PREdictive of phenoconversion in iRBD Italian STudy (FARPRESTO) is an ongoing Italian database aimed at identifying risk factors of phenoconversion, and eventually to ease clinical trial enrollment of well-characterized subjects.Methods: Polysomnography-confirmed iRBD patients were retrospectively and prospectively enrolled. Baseline harmonized clinical and nigrostriatal functioning data were collected at baseline. Nigrostriatal functioning was evaluated by dopamine transporter-single-photon emission computed tomography (DaT-SPECT) and categorized with visual semi-quantification. Longitudinal data were evaluated to assess phenoconversion. Cox regressions were applied to calculate hazard ratios.Results: 365 patients were enrolled, and 289 patients with follow-up (age 67.7 & PLUSMN; 7.3 years, 237 males, mean follow-up 40 & PLUSMN; 37 months) were included in this study. At follow-up, 97 iRBD patients (33.6%) phenoconverted to an overt synucleinopathy. Older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression, and visual semi-quantification of nigrostriatal functioning predicted phenoconversion. The remaining 268 patients are in follow-up within the FARPRESTO project.Conclusions: Clinical data (older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression) predicted phenoconversion in this multicenter, longitudinal, observational study. A standardized visual approach for semi-quantification of DaT-SPECT is proposed as a practical risk factor for phenoconversion in iRBD patients. Of note, non-converted and newly diagnosed iRBD patients, who represent a trial-ready cohort for upcoming disease-modification trials, are currently being enrolled and followed in the FARPRESTO study. New data are expected to allow better risk characterization

Twenty-four-hour blood pressure profile in idiopathic REM sleep behavior disorder

Study objectives: To determine whether autonomic dysfunction in idiopathic REM sleep behavior disorder (iRBD) affects circadian blood pressure (BP) profile. Methods: Twenty-one iRBD (mean age 68.8 ± 6.4, mean age at onset 62.2 ± 9.3), 21 drug-free de novo Parkinson's disease (PD) and 21 control participants (HCs), comparable for age and sex, underwent 24-h ambulatory BP monitoring. A prospective follow-up study was performed to evaluate the occurrence of neurodegenerative disorders in the iRBD cohort. Results: In the iRBD group, nighttime systolic BP (SBP) was higher (124.0 ± 20.0, p = .026), nocturnal BP decrease lower (4.0 ± 8.7% for SBP and 8.7 ± 8.0% for diastolic BP [DBP], p = .001), and nondipping status more frequent (71.4% for SBP and 52.4% for DBP; p = .001 and p = .01, respectively) than in the HCs. Reverse dipping of SBP was found in 23.8% (p = .048) of the iRBD participants. Nondipping status was not associated with differences in gender, age, disease duration, age at disease onset, UPDRS score, presence of antihypertensive therapy, or polysomnographic measures. Patients with PD showed daytime and nighttime BP profiles comparable to those observed in iRBD. A subgroup analysis considering only the participants without antihypertensive therapy (12 iRBD, 12 PD) showed results superimposable on those of the whole iRBD and PD groups. Longitudinal follow-up (mean 5.1 ± 1.9 years) showed no differences in BP profile at baseline between converters (n = 6) and nonconverters. Conclusions: Twenty-four-hour BP control was impaired in iRBD. This impairment, similar to patterns observed in de novo PD, consisted of reduced amplitude of nocturnal dipping and increased frequency of nondipping status. These findings could have implications for cardiovascular morbidity and mortality in iRBD

Evidence of Dissociated Arousal States During NREM Parasomnia from an Intracerebral Neurophysiological Study

Study Objectives: Arousal parasomnias are expressions of sleep/ wake state dissociations in which wakefulness and NREM sleep seem to coexist. We describe the results of a neurophysiological (intracerebral EEG) investigation that captured an episode of confusional arousal. Design: Observational analysis. Setting: Tertiary sleep center. Subject: A 20-year-old male with refractory focal epilepsy. Measurements and Results: The intracerebral EEG findings documented the presence of a local arousal of the motor and cingulate cortices associated with increased delta activity in the frontoparietal associative cortices; these findings were noted preceding the onset and persisting throughout the episode. Conclusions: The presence of dissociated sleep/wake states in confusional arousals is the expression not of a global phenomenon, but rather of the coexistence of different local states of being: arousal of the motor and cingulate cortices and inhibition of the associative ones. Whether this is an exclusive feature of NREM parasomnias, or a common substrate on which other triggering elements act, needs to be clarified

Assessment of cognitive profile as a prodromal marker of the evolution of rapid eye movement sleep behavior disorder

To search for a specific neuropsychological profile in idiopathic REM sleep behavior disorder (iRBD), able to predict the onset of neurodegenerative disorders

Neurophysiological evaluation of visual function in iRBD: potential role in stratifying RBD conversion risk

Study objectives: To evaluate neurophysiological alterations of visual function in idiopathic REM sleep Behavior Disorder (iRBD) both as markers and predictors of neurodegenerative disorders.Methods: In a longitudinal follow-up study of 46 consecutive iRBD patients (follow-up duration 8.4 +/- 3.4 years), the baseline parameters in luminance-contrast pattern (VEPp), red-green color (VEPc) and motion-onset (VEPm) Visual Evoked Potentials in iRBD were compared to early (ePD) and advanced (aPD) Parkinson's Disease subjects. Parameters of latency and amplitude of iRBD converters to neurodegenerative disease were compared with those of the non-converters.Results: The VEP P100 mean latency values for both eyes and for both stimulation checks (30' and 15') were significantly longer in all the three groups of patients as compared to controls; moreover latencies were longer in aPD than in the iRBD group who did not differ from the ePD group. The same held true when we analyzed the number of abnormal subjects belonging to each diagnostic group with a higher number of abnormal subjects in the aPD group compared to both the ePD and in iRBD groups. Chromatic and motion potentials were not different from controls and did not differ in the 3 diagnostic groups. The iRBD subjects who converted to a neurodegenerative disorder showed longer P100 latencies and a higher occurrence of VEPp abnormalities than those who did not convert. Again chromatic and motion VEPs were not different depending on conversion.Conclusions: In iRBD patients the detection of an abnormal VEPp should be considered as a red flag for possible synnucleinopathy, eventually contributing in stratifying the risk of phenoconversion. (C) 2021 Elsevier B.V. All rights reserved