Giuseppe Plazzi

• University of Bologna

Plain Language Summary What is this summary about? This is a plain language summary of a review article that looked at how different forms of a medicine called oxybate impact sleep in people with narcolepsy. People with narcolepsy often struggle with their sleep. They experience issues like sleep fragmentation or reduced sleep efficiency that may l...

The present study aimed to describe the prevalence rates of frequent (i.e., at least weekly) dream recall and nightmares with consideration for differences in age, gender and sleep duration in 16 countries using equivalent assessment methods. The study sample included 15,854 participants (69.9% women) aged 18–99 years ( M = 42.39, SD = 16.43) colle...

To study the impact of the COVID‐19 pandemic on sleep and circadian rhythms—two fundamental pillars for health—the collaboration International COVID‐19 Sleep Study (ICOSS) was established. The present overview comprehensively discusses the findings from this collaboration. Involving sleep researchers across the globe, ICOSS used a harmonised questi...

Background People with idiopathic/isolated REM sleep behavior disorder (iRBD) are highly heterogeneous, showing mild motor, cognitive, and dysautonomia symptoms. The aim of this study is to unveil the clinical heterogeneity of iRBD with a specific reference to overlapping features with prodromal Parkinson's disease (pPD) and prodromal dementia with...

Narcolepsy type 1 (NT1) is a rare neurological disorder characterized by excessive daytime sleepiness and cataplexy, thought to result from an autoimmune process targeting the hypothalamic hypocretin-producing neurons. Aiming to add clues to the latter hypothesis, we investigated circulating cell-free mitochondrial DNA (ccf-mtDNA) levels in cerebro...

Objectives: The present scoping review aims to map the existing evidence on psychological and behavioral interventions targeting patients with narcolepsy type 1 and type 2. Methods: A literature search was performed using the databases Scopus, PubMed, and PsycINFO. Studies were included if they (1) employed randomized controlled trials, non-randomi...

Sleep disturbances are common in individuals with first-episode psychosis (FEP) and have been identified as potential contributors to an increased risk of suicidal behavior. This systematic review aims to synthesize the existing evidence on the association between sleep disturbances and suicidal behavior in individuals experiencing FEP, a critical...

Social networking sites (SNS) use is associated with a range of positive outcomes, but a minority of vulnerable individuals experience problematic social networking site use (PSNSU). The relationship between PSNSU, sleep habits, and psychological distress remains insufficiently studied, particularly among older adults. As longer life expectancies a...

Background and Objectives The diagnosis of narcolepsy type 1 (NT1) currently requires the multiple sleep latency test (MSLT), or a nocturnal sleep-onset REM period (SOREMP) combined with typical cataplexy, or alternatively the determination of CSF hypocretin-1 (CSF-hcrt-1) deficiency. We evaluated the 24-hour polysomnography (PSG) recordings in adu...

Background: Adolescents with psychiatric disorders are at increased risk of suicide, with insomnia, depression, and social-personal factors playing pivotal roles. This study investigates the interplay between these factors in a sample of adolescent psychiatric inpatients in Italy, with a particular focus on their association with suicide attempts....

Introduction Narcolepsy type 1 (NT1) is a rare central sleep disorder characterized by a selective loss of hypocretin/orexin (hcrt)-producing neurons in the postero-lateral hypothalamus that project to widespread areas of the brain and brainstem. The aim of this study was to explore in a group of NT1 patients the metabolic alterations in the pons a...

Background Patients with Parkinson's Disease (PD) frequently exhibit non‐motor symptoms, particularly sleep disturbances. Sleep disorders in PD patients are intricately linked to the pathogenesis and progression of PD itself, exacerbating neurodegenerative processes and worsening patient quality of life. Objectives This review underscores the sign...

Background Spinal muscular atrophy (SMA) is a rare neuromuscular disorder characterized by progressive motor and respiratory dysfunction. Psychological disorders, including depression and suicidal ideation, frequently accompany severe chronic illnesses; however, in the context of SMA, evidence is scant. This study aimed to assess the presence of su...

The aim of the present study was to examine gender and age‐specific effects on subjective daytime sleepiness (as measured by the Epworth Sleepiness Scale), body weight and eating behaviour in patients with central disorders of hypersomnolence. Based on the European Narcolepsy Network database, we compared 1035 patients with narcolepsy type I and 50...

Study Objectives This study aimed to identify novel markers of narcolepsy type 1 (NT1) using between-nap opportunity periods (‘Lights On’) and in-nap opportunity periods (‘Lights Off’) features of Multiple Sleep Latency Test (MSLT) recordings. We hypothesized that NT1 could be identified both from sleep-wake instability and patterns of sleepiness d...

Introduction Adolescents’ health and well-being are seriously threatened by suicidal behaviors, which have become a severe social issue worldwide. Suicide is one of the leading causes of mortality for adolescents in low and middle-income countries, with approximately 67,000 teenagers committing suicide yearly. Although an association between sleep...

Stretch syncope (SS) is a benign, uncommon, distinct condition described mainly in adolescent males. It is responsible for paroxysmal events started by stereotyped stretching actions with neck hyperextension, culminating in alteration of consciousness. Motor manifestations are often present and may be associated with a generalized slowing of the el...

Study Objectives The role of actigraphy in central disorders of hypersomnolence (CDH) is expanding but evidence of reliability with polysomnography (PSG) is scarce and provided only during nighttime. We explored the agreement between actigraphy and continuous 24-hour PSG at CDH diagnosis. Methods Forty-four consecutive drug-naïve patients (28 narc...

Two recent studies suggested that the APOE ε4 haplotype was associated with increased α-synuclein pathology in cell and mouse models. Genetic variants in the SNCA region have strong association with Parkinson's disease (PD), Dementia with Lewy Bodies (DLB), and idiopathic REM Sleep Behavior Disorder (iRBD), while APOE is a genetic risk determinant...

The neurological condition known as narcolepsy type 1(NT1) is an uncommon condition marked by extreme daytime sleepiness, cataplexy, sleep paralysis, hallucinations, disrupted nocturnal sleep, and low or undetectable levels of orexin in the CSF fluid. NT1 has been hypothesized to be an immunological disorder; its treatment is currently only symptom...

Since the first description of narcolepsy at the end of the 19th Century, great progress has been made. The disease is nowadays distinguished as narcolepsy type 1 and type 2. In the 1960s, the discovery of rapid eye movement sleep at sleep onset led to improved understanding of core sleep-related disease symptoms of the disease (excessive daytime s...

Narcolepsy is a chronic central disorder of hypersomnolence most frequently arising during childhood/adolescence. This review article examined the literature concerning the etiology, prevalence, clinical course, and treatment of children with type 1 narcolepsy (NT1). Core symptoms of pediatric NT1 include excessive daytime sleepiness (EDS) and cata...

People with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) often report cognitive impairment which can be quite burdensome but is rarely evaluated in routine clinical practice. In this systematic review and meta-analysis, we assessed the nature and magnitude of cognitive impairment in NT1, NT2, and IH in studies c...

Background Preliminary data suggests that obesity might hasten the decline in mRNA vaccine-induced immunity against SARS-CoV-2. However, whether this renders individuals with obesity more susceptible to long COVID symptoms post-vaccination remains uncertain. Given sleep’s critical role in immunity, exploring the associations between obesity, probab...

Narcolepsy type 1 (NT1) is a chronic neurological disorder characterized by symptoms such as excessive daytime sleepiness, sudden sleep episodes, disrupted nocturnal sleep, cataplexy, sleep paralysis, and hypnagogic hallucinations, which significantly impact the overall well-being and quality of life of individuals. While psychological factors have...

Objective Sleep problems constitute a common and heterogeneous complaint in pediatric palliative care (PPC), where they often contribute to disease morbidity and cause additional distress to children and adolescents and their families already facing the burden of life-threatening and life-limiting conditions. Despite the significant impact of slee...

Introduction Increased narcolepsy type 1 (NT1) incidence rates have been reported globally in 2010, and were linked to the type A H1N1 2009-2010 influenza pandemic and Pandemrix vaccination. A European child-specific NT1 incidence peak was additionally observed in 2013 post the H1N1 pandemic. Thus, the relationship between NT1 and influenza infecti...

Introduction Restless Legs Syndrome (RLS) is a widely prevalent and complex neurological disorder. Despite notable advancements in managing RLS, the disorder continues to face challenges related to its recognition and management. Objective This study seeks to gain comprehensive insights into the knowledge and clinical practices among Italian neuro...

Objective: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). Methods: In this multicenter study of the International RBD study group, 173 patients...

Narcolepsy type 1 is a central disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy and other rapid eye movement sleep-related manifestations. Neurophysiological studies suggest that narcolepsy type 1 patients may experience impairment in emotional processing due to structural and functional changes in limbic structu...

The association between nightmare frequency (NMF) and suicidal ideation (SI) is well known, yet the impact of the COVID-19 pandemic on this relation is inconsistent. This study aimed to investigate changes in NMF, SI, and their association during the COVID-19 pandemic. Data were collected in 16 countries using a harmonised questionnaire. The sample...

Narcolepsy type 1 is a chronic central disorder of hypersomnolence, and it is frequently accompanied by overweight, but the association between narcolepsy type 1 and eating disorders is controversial. Our study aims to compare patients with narcolepsy type 1 and controls on the symptomatology of eating disorders and to evaluate the association betw...

Background Isolated rapid‐eye‐movement sleep behavior disorder (iRBD) is associated with a high risk for phenoconversion to a neurodegenerative disorder, but the optimal approach for disclosure of this risk to patients is still debated. Objectives The aim of this study was to explore views and experiences of iRBD experts regarding risk disclosure....

Accurate measurement of habitual sleep duration (HSD) is crucial for understanding the relationship between sleep and health. This study aimed to assess the bias and agreement limits between two commonly used short HSD self-report methods, considering sleep quality (SQ) and social jetlag (SJL) as potential predictors of bias. Data from 10,268 parti...

To investigate potential sex-related differences in patients with narcolepsy type 1, we carried out an analysis of baseline data from 93 women and 89 men with narcolepsy type 1 who participated in the TElemedicine for NARcolepsy (TENAR) trial. The following data were considered: sociodemographics; diagnostic (disease history, polysomnography, orexi...

Background and Objectives Narcolepsy type 1 (NT1) is still largely underdiagnosed or diagnosed too late in children. Difficulties in obtaining rapid and reliable diagnostic evaluations of the condition in clinical practice partially explain this problem. Predictors of NT1 include cataplexy and sleep-onset REM periods (SOREMPs), documented during no...

The aim of this study was to assess work productivity and activity impairments and to explore their association with excessive daytime sleepiness, body mass index (BMI), depression, and anxiety in patients with narcolepsy type 1. We carried out a cross‐sectional study in which patients with narcolepsy type 1 and matched controls for sex, age, and e...

Study objectives: To examine body mass index (BMI) changes associated with sodium oxybate treatment (SXB) in pediatric patients with narcolepsy with cataplexy who participated in a double-blind, placebo-controlled, randomized withdrawal study and an open-label continuation period (OLC). Methods: Participants were aged 7-16 years at screening. SX...

Glycoproteomic analysis is always challenging because of low abundance and complex site-specific heterogeneity. Glycoproteins are involved in various biological processes such as cell signaling, adhesion, and cell–cell communication and may serve as potential biomarkers when analyzing different diseases. Here, we investigate glycoproteins in narcol...

Narcolepsy type 1 (NT1) is a central disorder of hypersomnolence often arising inchildhood and adolescence. NT1 has a significant, but poorly defined, psychologicalimpact. We aimed to investigate the psycho-social functioning of children and ado-lescents with NT1. We performed a cross-sectional, child and parent-reported ques-tionnaire survey in 37...

Objective Individuals with fibromyalgia report alarming levels of suicidal ideation, and comorbidity with other chronic health conditions such as obesity - a risk factor for suicidal ideation per se- could further complicate the clinical picture. The aim of this study is to determine, in a sample of women with fibromyalgia and comorbid obesity, the...

Study objectives: Preliminary evidence suggests that the risk of Long COVID is higher among people with pre-existing medical conditions. Based on its proven adjuvant role in immunity, habitual sleep duration may alter the risk for developing Long COVID. The objective of this study was to determine whether the odds of Long COVID are higher amongst...

The Coronavirus 2019 (COVID‐19) pandemic significantly influenced physical and mental health worldwide. The present study aimed to investigate changes in sleep problems across three waves of the COVID‐19 pandemic, and to identify potential predictors of the inter‐individual variability around these changes, with a particular focus on the role of de...

Study objectives: Pseudocataplexy is a rare functional neurological disorder that mimics cataplexy, pathognomonic for narcolepsy type 1 (NT1). We describe the psychiatric comorbidity and personality traits of patients with pseudocataplexy versus NT1 cases. Methods: The case-control observational study enrolled consecutive patients with pseudocat...

DNA methyltransferase type 1 (DNMT1) is a major enzyme involved in maintaining the methylation pattern after DNA replication. Mutations in DNMT1 have been associated with autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN). We used fibroblasts, induced pluripotent stem cells (iPSCs) and induced neurons (iNs) generated from pati...

Introduction: Idiopathic/isolated 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...

INTRODUCTION Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a powerful early predictor of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). This provides an opportunity to directly observe the evolution of prodromal DLB and to identify which cognitive variables are the strongest predictors of evolving dementia....

Synucleinopathies-related disorders such as Lewy body dementia (LBD) and isolated/idiopathic REM sleep behavior disorder (iRBD) have been associated with neuroinflammation. In this study, we examined whether the human leukocyte antigen (HLA) locus plays a role in iRBD and LBD. In iRBD, HLA-DRB1*11:01 was the only allele passing FDR correction (OR =...

Introduction Narcolepsy Type 1 (NT1) is a rare hypersomnia of central origin linked to hypocretin deficiency, most frequently arising at pediatric age. NT1 could be associated with endocrine comorbidities involving the neuroendocrine axis, predominantly obesity, and Central Precocious Puberty (CPP). The primary aim of this study is the evaluation o...

Purpose COVID-19 pandemic waves have strongly influenced individuals’ behaviors and mental health. Here, we analyzed longitudinal data collected in the Spring 2020 and 2021 from a large Italian sample with the aim of assessing changes in dream features between the first and third wave. Specifically, we evaluated the modifications of pandemic dream...

Disturbed nocturnal sleep contributes to the central sensitization of pain, thus predisposing to orofacial pain. Central disorders of hypersomnolence are characterized by excessive daytime sleepiness (EDS) not linked to impairment of nocturnal sleep or misaligned circadian rhythms. The main disorder of this group is narcolepsy type 1 (NT1), which s...

Introduction The COVID-19 pandemic caused several psychological consequences for the general population. In particular, long-term and persistent psychopathological detriments were observed in those who were infected by acute forms of the virus and need specialistic care in the Intensive Care Unit (ICU). Imagery rehearsal therapy (IRT) has shown pro...

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals withi...

Background: The COVID-19 pandemic and related restriction measures have affected our daily life, sleep, and circadian rhythms worldwide. Their effects on hypersomnolence and fatigue remain unclear. Methods: The International COVID-19 Sleep Study questionnaire which included items on hypersomnolence such as excessive daytime sleepiness (EDS), and...

The COVID-19 pandemic posed a significant challenge to the global organization of health systems. The reallocation and concentration of available resources on the management of COVID-19 had a significant impact on all other health conditions due to the suspension or cancellation of screening and routine examinations, the reduction of referrals, and...

Background: The gold standard for the diagnosis of sleep bruxism (SB) is laboratory polysomnography (L-PSG) recording. However, many clinicians still define SB using patients' self-assessment and/or clinical tooth wear (TW). The purpose of this cross-sectional controlled study was to compare the prevalence of TW, head-neck muscles sensitivity and...

Actigraphy has a consolidated role in Insomnia and Circadian Rhythm Sleep-Wake Disorders (CRSWD) and recent studies have highlighted the use of actigraphy for narcolepsy and REM sleep behaviour disorder (RBD). This review aims at summarising the results of studies published over the last decade regarding the use of actigraphy. Thirty-five studies p...

Background: Narcolepsy is a life-long disorder characterised by excessive daytime sleepiness and cataplexy, often arising in childhood or adolescence. Pitolisant, a selective histamine H3 receptor inverse agonist, has been approved in Europe and USA for adults with narcolepsy with or without cataplexy, with a favourable safety profile. This phase...

The neurodegenerative synucleinopathies, including Parkinson’s disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore r...

Background: First symptoms of narcolepsy mostly present during childhood. Pharmacological management options in children are limited, also due to approval status. Pitolisant is an inverse histamine 3 receptor agonist and has been approved for the treatment of adult narcolepsy with or without cataplexy by EMA and FDA. Clinical experience indicates...

NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C (NPC), a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed...

Narcolepsy type 1 (NT1) is the most common type of narcolepsy known to be caused by the loss of specific neurons responsible for producing peptide neurotransmitters (orexins/hypocretins), resulting in a sleep-wake cycle disorder. It is characterized by its association with cataplexy and abnormalities in rapid eye movement. To date, no cure has been...

Isolated/idiopathic REM sleep behavior disorder (iRBD) and Lewy body dementia (LBD) are synucleinopathies that have partial genetic overlap with Parkinson’s disease (PD). In this study, we examined if the human leukocyte antigen ( HLA ) locus plays a similar role in iRBD, LBD and PD. The DQA1*01:02∼DQB1*06:02∼DRB1*15:01 haplotype is associated with...

Study objectives: This study aimed to explore resilience and its possible association with sociodemographic and clinical features in patients with narcolepsy type 1 (NT1). Methods: Cross-sectional study involving patients with NT1 and age/sex-matched controls (comparison group). Sociodemographic and clinical data were collected through semi-stru...

Background and objective: Daridorexant is a dual orexin receptor antagonist for the treatment of insomnia. In two phase III, 12-week studies in patients with insomnia disorder, daridorexant improved sleep and daytime functioning while maintaining a favorable safety profile. The objective of this 40-week extension study was to assess the long-term...

Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD ri...

Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD ri...

Narcolepsy type 1 is a central disorder of hypersomnolence characterized by excessive daytime sleepiness, rapid eye movement sleep-related manifestations, and cataplexy. In the current literature there is general agreement regarding neural correlates of Narcolepsy type 1 that appear to be related to anatomical and functional abnormalities in the hy...

The present study had two main aims. First, to investigate whether shift/night workers had a higher prevalence and severity of COVID-19 compared with day workers. Second, to investigate whether people regularly working in face-to-face settings during the pandemic exhibited a higher prevalence and severity of COVID-19 compared with those having no n...

NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C, a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed to ev...

Recent investigations show that many people affected by SARS‐CoV2 (COVID‐19) report persistent symptoms 2–3 months from the onset of the infection. Here, we report the Italian findings from the second International COVID‐19 Sleep Study survey, aiming to investigate sleep and dream alterations in participants with post‐acute symptoms, and identify t...

Objective To investigate adolescents’ and parents’ preferences concerning information on narcolepsy. Methods During a one-year cross-sectional study, adolescents (12–20 years old) with narcolepsy and parents attending the Narcolepsy Center of Bologna (Italy) were invited to fill in a questionnaire including 28 pieces of information regarding narco...

Background: Narcolepsy type 1 (NT1) is a rare neurological sleep disorder caused by the loss of neurons that produce hypocretin-a peptide that plays a crucial role in addictive behaviors. We aimed to compare, for the first time, levels of problematic online gaming, problematic social media use, and compulsive Internet use between NT1 patients and...

Many people report suffering from post‐acute sequelae of COVID‐19 or “long‐COVID”, but there are still open questions on what actually constitutes long‐COVID and how prevalent it is. The current definition of post‐acute sequelae of COVID‐19 is based on voting using the Delphi‐method by the WHO post‐COVID‐19 working group. It emphasizes long‐lasting...

Study objectives The assay currently used worldwide to measure cerebrospinal fluid hypocretin-1 (CSF-hcrt-1) for diagnosing narcolepsy uses a competitive radioimmunoassay with polyclonal anti-hcrt-1 antibodies. This assay detects multiple hypocretin-1 immunoreactive species in the CSF that are all derived from full-length hcrt-1. We aimed to revali...