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

Influencing dreams through sensory stimulation - manuscript

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Influencing dreams through sensory stimulation - appendices

Appendices complementing the manuscrip

Influencing dreams through sensory stimulation: a systematic review

Systematic review on the subject of sensory-dependent dream changes (SDDCs) [manuscript]. Recapitulative tables for all selected publications are available [supplementary materials]. A novel tool for evaluating the methodological reliability of dream-related publications is presented, based on the Downs & Black methological assessment checklist (1998) [appendices]

Influencing dreams through sensory stimulation: a systematic review

Sleep is commonly regarded as a state of disconnection from the environment. Yet, instances of external sensory stimuli affecting the course of dreams have been reported for centuries. Importantly, understanding the impact of external stimuli on dreams could shed light on the origin and generation of dreams, the functional mechanisms that preserve sleep continuity, and the processes that underlie conscious awareness. Moreover, the possibility of using sensory stimuli for dream engineering could potentially benefit patients suffering from alterations in the intensity or content of sleep conscious experiences. Here, we performed a systematic review following PRISMA guidelines to evaluate the robustness of the current evidence regarding the influence of external sensory stimulation during sleep on dreams experiences. In a literature search using PsycNET, PubMed, ScienceDirect, and Scopus, we selected any experimental work presenting dream data obtained from a confirmed sleep episode during which visual, auditory, olfactory, gustatory, or somatosensory stimulation was administered. A methodological assessment of the included studies was performed using an adapted version of the Downs and Black’s (1998) checklist. Fifty-one publications met the inclusion criteria, of which 21 reported data related to auditory stimulation, 10 to somatosensory stimulation, 8 to olfactory stimulation, 4 to visual stimulation, 2 to vestibular stimulation, and 1 to multi-modal stimulation (audio-visual). Furthermore, 9 references involved pre-conditioned associative stimulation procedures: 6 relied on targeted memory reactivation protocols and 3 on targeted lucid reactivation protocols. The reported frequency of stimulus-dependent dream changes across studies ranged from 0% to ~90%. Such a variability likely reflects the considerable heterogeneity of experimental and methodological approaches. Overall, the literature analysis identified a lack of substantial understanding of the key mechanisms, functions, and correlates of stimulus-dependent dream changes. We believe that a paradigm shift is required for meaningful and significant advancement in the field. We hope that this review will serve as a starting point for such a shift

Influencing dreams through sensory stimulation - supplementary materials

Recapitulative tables supplementing the manuscrip

Elucidating the molecular mechanisms underlying the biological activity of rescuing peptides in MELAS mitochondrial disease

Mitochondrial Encephalopathy with Lactic Acidosis and Stroke like Episodes (MELAS) is a mitochondrial disease caused by point mutations in the tRNALeu(UUR) with a prevalence in position 3243 (A>G). These mutations cause severe impairment of mitochondrial protein synthesis due to alterations of the mutated tRNA such as reduced aminoacylation and lack of post-transcriptional modification. It has been shown that overexpression of leucyl-tRNA-synthetase (mt-LeuRS) is able to rescue defects of pathogenic mutation of tRNALeu(UUR) in MELAS cybrids [1]. The rescuing activity of human mt-LeuRS resides in a small (<70 amino acids) part of the carboxy-terminal domain (Cterm) of the enzyme and in short (15-16 aa) C-term-derived peptides. However, the molecular mechanisms underlying the rescuing process are still unknown. On these bases, we started a project aimed at elucidating the ability of mt-LeuRS C-term and its derived peptides to correct the pathological phenotype in MELAS. To address this issue we intend: i) to investigate in vivo the interactions of rescuing molecules with mutated mt-tRNA; ii) to study the effect of overexpression of rescuing molecules on the rate of synthesis and stability of de novo synthesized mt-polypeptides; iii) to investigate the effect of rescuing molecules on the steady-state level, the aminoacylation level and the post-transcriptional modifications of the mutated tRNA. To date we have characterized the profile of the de novo synthesized mt-polypeptides from MELAS cybrids, finding an overall decreased rate of synthesis and the appearance of aberrant mitochondrial translation product. We have also observed a decreased steady-state level of NDUFB8 (Complex I) and COXI (Complex IV). Finally, we have demonstrated in MELAS cybrids constitutively expressing C-term, the existence of a preferential interaction between Cterm polypeptide and tRNALeu(UUR) by means of RNA immunoprecipitation experiments

Sleep effects of Ketogenic diet in pediatric patients with migraine: Preliminary data of a prospective study

Objective/background: Ketogenic dietary therapies' effects on sleep have been poorly investigated up to date. Preliminary results of a prospective study aimed at evaluating possible sleep changes in pediatric patients with migraine treated with classic ketogenic diet are presented. Patients/methods: Included patients were aged 14-18 years and had a diagnosis of chronic migraine. A customized classic ketogenic diet was drawn up for all patients and all participants underwent neurological, nutritional and subjective and objective sleep assessment at baseline and after three months of follow-up (standardized sleep questionnaires, polysomnography, actigraphy). Results: The majority of patients reported an improvement in migraine symptoms and quality of life. As far as sleep effects, a possible sleep stabilization was evidenced according to actigraphic data, and polysomnographic data showed a slight increase in total sleep time and sleep efficiency together with a reduction in waking time during night and a trend of NREM stage 1 decrease and REM increase. Conclusions: Future analyses on a broader population are needed to shed light on the ketogenic dietary therapies' effects on sleep and future research should be devoted to identify influence of possible individual and diet characteristics, and biochemical related changes

The effects of ketogenic dietary therapies on sleep: A scoping review

: Sleep problems are common in neurological conditions for which ketogenic dietary therapies (KDTs) are recognised as an effective intervention (drug-resistant epilepsy, autism spectrum disorder, and migraine). Given the composite framework of action of ketogenic dietary therapies, the prevalence of sleep disturbance, and the importance of sleep regulation, the present scoping review aimed at identifying and mapping available evidence of the effects of ketogenic dietary therapies on sleep. A comprehensive web-based literature search was performed retrieving publications published to June 2023 using PubMed and Scopus, yielding to 277 records. Twenty papers were finally selected and included in the review. Data were abstracted by independent coders. High variability was identified in study design and sleep outcome evaluation among the selected studies. Several changes in sleep quality and sleep structure under ketogenic dietary therapies were found, namely an improvement of overall sleep quality, improvement in the difficulty falling asleep and nighttime awakenings, improvement in daytime sleepiness and an increase of REM sleep. The relevance and possible physiological explanations of these changes, clinical recommendations, and future directions in the field are discussed