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Article ; Online: The importance of measuring cerebrospinal-fluid orexin levels: The "forgotten" studies in obstructive sleep apnea.

Liguori, Claudio

2022 Volume 102, Page(s) 31

MeSH term(s)	Humans ; Orexins ; Sleep Apnea, Obstructive/diagnosis ; Neuropeptides
Chemical Substances	Orexins ; Neuropeptides
Language	English
Publishing date	2022-12-24
Publishing country	Netherlands
Document type	Letter ; Comment
ZDB-ID	2012041-2
ISSN	1878-5506 ; 1389-9457
ISSN (online)	1878-5506
ISSN	1389-9457
DOI	10.1016/j.sleep.2022.12.020
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Article ; Online: Daridorexant treatment for chronic insomnia: a real-world retrospective single-center study.

Fernandes, Mariana / Placidi, Fabio / Mercuri, Nicola Biagio / Liguori, Claudio

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2024

Abstract: Introduction: Chronic insomnia disorder (CID) significantly impacts well-being and daily functioning. Daridorexant, a double orexin receptor blocker, has shown efficacy in randomized clinical trials and has been recently approved for the treatment of ... ...

Abstract	Introduction: Chronic insomnia disorder (CID) significantly impacts well-being and daily functioning. Daridorexant, a double orexin receptor blocker, has shown efficacy in randomized clinical trials and has been recently approved for the treatment of CID in adult patients. This retrospective observational study aimed to describe real-world data on daridorexant effectiveness and safety in adult patients with CID. Methods: Consecutive patients initiating on-label daridorexant at the Sleep Medicine Centre, University Hospital of Rome Tor Vergata were enrolled. Baseline and 30-day follow-up (FU) evaluations included patients' and CID characteristics, comorbidities, and clinicians' and patients' subjective ratings of changes with the Clinical and Patient Global Impression-Improvement scores (CGI-Is and PGI-Is), as well as Insomnia Severity Index (ISI) scores in a subgroup of patients. Results: Sixty-nine patients initiated 50-mg daily dosage. At FU, 58% of both patients and clinicians rated CID as improved on CGI-Is and PGI-Is, with no differences based on comorbidities, sex, or number of previous medications. No significant predictors of CGI-Is and PGI-Is improvement were identified. At FU, ISI scores (n = 24) significantly decreased from 18.25 ± 3.21 to 12.08 ± 6.12 (Z = 8.000; p < 0.001). Of these, eight patients (33.3%) had absence of insomnia symptoms, and no patients reported a worsening in ISI score categories. Conclusions: This study suggests daridorexant to be effective and safe in real-world CID treatment whether used as a first-ever treatment, switch, or add-on, as reflected by subjective and objective measures and the absence of serious treatment-related adverse events. Future research on larger cohorts should explore daridorexant potential across diverse patient characteristics.
Language	English
Publishing date	2024-01-27
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-024-07326-w
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Article ; Online: Role of the orexin system in the bidirectional relation between sleep and epilepsy: New chances for patients with epilepsy by the antagonism to orexin receptors?

Berteotti, Chiara / Calvello, Carmen / Liguori, Claudio

Epilepsia

2023 Volume 64, Issue 8, Page(s) 1991–2005

Abstract: Epilepsy is a common neurological disorder, affecting patients of all ages, reducing the quality of life, and associated with several comorbidities. Sleep impairment is a frequent condition in patients with epilepsy (PWE), and the relation between sleep ... ...

Abstract	Epilepsy is a common neurological disorder, affecting patients of all ages, reducing the quality of life, and associated with several comorbidities. Sleep impairment is a frequent condition in patients with epilepsy (PWE), and the relation between sleep and epilepsy has been considered bidirectional, as one can significantly influence the other, and vice versa. The orexin system was described more than 20 years ago and is implicated in several neurobiological functions other than in controlling the sleep-wake cycle. Considering the relation between epilepsy and sleep, and the significant contribution of the orexin system in regulating the sleep-wake cycle, it is conceivable that the orexin system may be affected in PWE. Preclinical studies investigated the impact of the orexin system on epileptogenesis and the effect of orexin antagonism on seizures in animal models. Conversely, clinical studies are few and propose heterogeneous results also considering the different methodological approaches to orexin levels quantification (cerebrospinal-fluid or blood samples). Because orexin system activity can be modulated by sleep, and considering the sleep impairment documented in PWE, the recently approved dual orexin receptor antagonists (DORAs) have been suggested for treating sleep impairment and insomnia in PWE. Accordingly, sleep improvement can be a therapeutic strategy for reducing seizures and better managing epilepsy. The present review analyzes the preclinical and clinical evidence linking the orexin system to epilepsy, and hypothesizes a model in which the antagonism to the orexin system by DORAs can improve epilepsy by both a direct and a sleep-mediated (indirect) effect.
MeSH term(s)	Animals ; Orexins ; Orexin Receptors/physiology ; Quality of Life ; Sleep/physiology ; Epilepsy/complications ; Epilepsy/drug therapy ; Orexin Receptor Antagonists/therapeutic use ; Orexin Receptor Antagonists/pharmacology ; Seizures/drug therapy
Chemical Substances	Orexins ; Orexin Receptors ; Orexin Receptor Antagonists
Language	English
Publishing date	2023-06-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17661
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Article: Orexin and Alzheimer's Disease.

Liguori, Claudio

Current topics in behavioral neurosciences

2017 Volume 33, Page(s) 305–322

Abstract: Alzheimer's disease (AD) is the most frequent age-related dementia. It prevalently causes cognitive decline, although it is frequently associated with secondary behavioral disturbances. AD neurodegeneration characteristically produces a remarkable ... ...

Abstract	Alzheimer's disease (AD) is the most frequent age-related dementia. It prevalently causes cognitive decline, although it is frequently associated with secondary behavioral disturbances. AD neurodegeneration characteristically produces a remarkable destruction of the sleep-wake cycle, with diurnal napping, nighttime arousals, sleep fragmentation, and REM sleep impairment. It was recently hypothesized that the orexinergic system was involved in AD pathology. Accordingly, recent papers showed the association between orexinergic neurotransmission dysfunction, sleep impairment, and cognitive decline in AD. Orexin is a hypothalamic neurotransmitter which physiologically produces wakefulness and reduces REM sleep and may alter the sleep-wake cycle in AD patients. Furthermore, the orexinergic system seems to interact with CSF AD biomarkers, such as beta-amyloid and tau proteins. Beta-amyloid accumulation is the main hallmark of AD pathology, while tau proteins mark brain neuronal injury due to AD pathology. Investigations so far suggest that orexinergic signaling overexpression alters the sleep-wake cycle and secondarily induces beta-amyloid accumulation and tau-mediated neurodegeneration. Therefore, considering that orexinergic system dysregulation impairs sleep-wake rhythms and may influence AD pathology, it is hypothesized that orexin receptor antagonists are likely potential preventive/therapeutic options in AD patients.
MeSH term(s)	Alzheimer Disease/metabolism ; Alzheimer Disease/physiopathology ; Animals ; Brain/metabolism ; Brain/physiopathology ; Humans ; Orexins/metabolism
Chemical Substances	Orexins
Language	English
Publishing date	2017-09-25
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	1866-3370
ISSN	1866-3370
DOI	10.1007/7854_2016_50
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Article ; Online: Sleep Biomarkers for Predicting Cognitive Decline and Alzheimer's Disease: A Systematic Review of Longitudinal Studies.

Carpi, Matteo / Fernandes, Mariana / Mercuri, Nicola Biagio / Liguori, Claudio

Journal of Alzheimer's disease : JAD

2023 Volume 97, Issue 1, Page(s) 121–143

Abstract: Background: Sleep disturbances are considered a hallmark of dementia, and strong evidence supports the association between alterations in sleep parameters and cognitive decline in patients with mild cognitive impairment and Alzheimer's disease (AD).: ... ...

Abstract	Background: Sleep disturbances are considered a hallmark of dementia, and strong evidence supports the association between alterations in sleep parameters and cognitive decline in patients with mild cognitive impairment and Alzheimer's disease (AD). Objective: This systematic review aims to summarize the existing evidence on the longitudinal association between sleep parameters and cognitive decline, with the goal of identifying potential sleep biomarkers of AD-related neurodegeneration. Methods: Literature search was conducted in PubMed, Web of Science, and Scopus databases from inception to 28 March 2023. Longitudinal studies investigating the association between baseline objectively-measured sleep parameters and cognitive decline were assessed for eligibility. Results: Seventeen studies were included in the qualitative synthesis. Sleep fragmentation, reduced sleep efficiency, reduced REM sleep, increased light sleep, and sleep-disordered breathing were identified as predictors of cognitive decline. Sleep duration exhibited a U-shaped relation with subsequent neurodegeneration. Additionally, several sleep microstructural parameters were associated with cognitive decline, although inconsistencies were observed across studies. Conclusions: These findings suggest that sleep alterations hold promise as early biomarker of cognitive decline, but the current evidence is limited due to substantial methodological heterogeneity among studies. Further research is necessary to identify the most reliable sleep parameters for predicting cognitive impairment and AD, and to investigate interventions targeting sleep that can assist clinicians in the early recognition and treatment of cognitive decline. Standardized procedures for longitudinal studies evaluating sleep and cognition should be developed and the use of continuous sleep monitoring techniques, such as actigraphy or EEG headband, might be encouraged.
MeSH term(s)	Humans ; Alzheimer Disease/psychology ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/complications ; Sleep ; Cognition ; Biomarkers ; Longitudinal Studies
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-12-04
Publishing country	Netherlands
Document type	Systematic Review
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-230933
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Article: Upper Airway Characteristics and Morphological Changes by Different MADs in OSA Adult Subjects Assessed by CBCT 3D Imaging.

Venza, Nicolò / Malara, Arianna / Liguori, Claudio / Cozza, Paola / Laganà, Giuseppina

Journal of clinical medicine

2023 Volume 12, Issue 16

Abstract: This study aimed to analyse the effectiveness of four different designs of the Mandibular Advancement Device (MAD) and the morphological changes on upper airway characteristics of Obstructive Sleep Apnea (OSA) patients inducted by each of them, detected ... ...

Abstract	This study aimed to analyse the effectiveness of four different designs of the Mandibular Advancement Device (MAD) and the morphological changes on upper airway characteristics of Obstructive Sleep Apnea (OSA) patients inducted by each of them, detected by Cone Beam Computer Tomography (CBCT) 3D imaging. Twenty-two patients were recruited after an OSA diagnosis with PSG. Four different customised and titratable MADs were used and an initial CBCT scan was obtained for each patient. Six months after the end of the MAD titration phase, all the subjects performed a second PSG with the MAD in situ; the second PSG showed an Apnoea-Hypopnoea Index (AHI) of <5 or a decrease of 50% in AHI when compared with the initial AHI. Moreover, a second CBCT scan with the MAD in situ was performed. DICOM files were imported into the airway analysis software programme and the pharyngeal area around the oropharynx was highlighted. The area and volume of the oropharynx with and without the device was evaluated. A considerable improvement of the airway was observed (+33.76%), and a significant difference in the enlargement ratio between the posterior soft palate (+32.41%) and the posterior tongue (+36.96%) region was also found. The greatest increase in airway volume was achieved in patients treated with the MAD Forward and TAP (+42.77% and +41.63%, respectively). MAD therapy is effective to treat moderate to severe OSA with an increased upper airway volume. The design of the MAD can influence the effectiveness of the treatment.
Language	English
Publishing date	2023-08-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12165315
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Article ; Online: Sex differences in Parkinson's disease-related non motor symptoms: a focus on sleep problems.

Bovenzi, Roberta / Conti, Matteo / De Franco, Valentino / Pierantozzi, Mariangela / Schirinzi, Tommaso / Cerroni, Rocco / Stefani, Alessandro / Mercuri, Nicola Biagio / Liguori, Claudio

Acta neurologica Belgica

2024

Abstract: Parkinson's disease (PD) symptomatology differs between females and males, yet the contribution of sex on sleep problems needs further analysis. Here, we aimed to investigate sex-specific patterns in the relationship between sleep problems, assessed ... ...

Abstract	Parkinson's disease (PD) symptomatology differs between females and males, yet the contribution of sex on sleep problems needs further analysis. Here, we aimed to investigate sex-specific patterns in the relationship between sleep problems, assessed using the Parkinson's disease sleep scale (PDSS-2), non motor symptoms (NMS), measured by the NMS scale (NMSS), and health-related quality of life (HR-QoL), evaluated by the Parkinson's disease questionnaire (PDQ-39), in a large cohort of PD patients. One-hundred-fifty-four PD patients were included in the study. Female PD patients (n = 62) exhibited a higher prevalence of sleep problems than males (n = 92), with nocturnal motor-related sleep issues being the most frequent. Sleep disturbances differently correlated with a range of NMS between the two sexes. In females, sleep problems mostly correlated with pain; on the other hand, sleep disturbances were linked to a frailer phenotype characterized by global dysautonomia, perception disturbances, and impaired cognitive function in males. Whether female PD patients experienced a lower HR-QoL than males, sleep disturbances were associated with a worse HR-QoL in both sexes. In conclusion, sleep problems in PD differently burden the two sexes, suggesting possible different etiopathogenesis, diagnostic investigations, and possibly tailored approaches.
Language	English
Publishing date	2024-04-04
Publishing country	Italy
Document type	Journal Article
ZDB-ID	127315-2
ISSN	2240-2993 ; 0300-9009
ISSN (online)	2240-2993
ISSN	0300-9009
DOI	10.1007/s13760-024-02535-8
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Article: Assessment of Psychometric Characteristics of Parkinson's Disease Sleep Scale 2 and Analysis of a Cut-Off Score for Detecting Insomnia in Italian Patients with Parkinson's Disease: A Validation Study.

Liguori, Claudio / Frontani, Francesco / Francescangeli, Giulia / Pierantozzi, Mariangela / Cerroni, Rocco / Schirinzi, Tommaso / Stefani, Alessandro / Mercuri, Nicola Biagio / Galeoto, Giovanni

Journal of personalized medicine

2024 Volume 14, Issue 3

Abstract: Introduction: Sleep disorders are frequent non-motor symptoms affecting patients with Parkinson's disease (PD). Insomnia represents the most common sleep disorder. Parkinson's disease Sleep Scale 2 (PDSS-2) is a specific tool to investigate sleep ... ...

Abstract	Introduction: Sleep disorders are frequent non-motor symptoms affecting patients with Parkinson's disease (PD). Insomnia represents the most common sleep disorder. Parkinson's disease Sleep Scale 2 (PDSS-2) is a specific tool to investigate sleep problems in PD. The General Sleep Disturbances Scale (GSDS) was a general scale validated for the Italian population. Our goal was to assess the psychometric characteristics of PDSS-2 and the GSDS in this population, calculating a cut-off score for insomnia symptoms by using subitems of PDSS-2. Methods: Patients admitted at the PD Unit of the Hospital of Rome Tor Vergata outpatient clinic and those afferent to PD associations were asked to complete PDSS-2 and GSDS to be correlated to identify a cut-off for insomnia symptoms. Items 1,2,3,8,13 of PDSS-2 were used to detect insomnia. An ROC curve to assess a cut-off score for insomnia was determined. A cross-cultural analysis of PD population characteristics was performed. Results: In total, 350 PD patients were recruited. Cronbach's alpha was high for the total score (0.828 for PDSS-2 and 0.832 for GSDS). A cross-cultural analysis did not show any significant Discussion: PDSS-2 is demonstrated to be a valid, specific tool to address sleep disturbances in PD patients. A cut-off score of 10 for items 1,2,3,8,13 was identified for detecting insomnia symptoms in PD patients.
Language	English
Publishing date	2024-03-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm14030298
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Article ; Online: Effects of anti-seizure medications on sleep architecture and daytime sleepiness in patients with epilepsy: A literature review.

Liguori, Claudio / Toledo, Manuel / Kothare, Sanjeev

Sleep medicine reviews

2021 Volume 60, Page(s) 101559

Abstract: Anti-seizure medications (ASMs) may improve or be detrimental to sleep. A literature review (as an update to the 2014 review by Jain and Glauser [https://doi.org/10.1111/epi.12478]) of 25 ASMs of interest (articles from 12 ASMs included) on the effect of ...

Abstract	Anti-seizure medications (ASMs) may improve or be detrimental to sleep. A literature review (as an update to the 2014 review by Jain and Glauser [https://doi.org/10.1111/epi.12478]) of 25 ASMs of interest (articles from 12 ASMs included) on the effect of ASMs/non-drug treatments on sleep in patients with epilepsy was conducted. The most common objective instrument was polysomnography, and the most common subjective measures were the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index. Eslicarbazepine acetate, lacosamide, and perampanel improved or had no effect on sleep. Perampanel was associated with low incidence of insomnia, and lacosamide with low incidence of daytime sleepiness adverse events. Clonazepam, felbamate, lamotrigine, oxcarbazepine, and phenobarbital worsened or had no effect on sleep. Lamotrigine may be associated with insomnia risk and phenobarbital with daytime sleepiness. Data for valproic acid were mixed. Overall, cannabidiol, carbamazepine, and levetiracetam had no effect on sleep. Epilepsy surgery may benefit sleep in patients with a good surgical outcome. Some ASMs, and, possibly, epilepsy surgery, may have positive effects on sleep, possibly linked to achieving seizure control. Nonetheless, other ASMs may worsen sleep in some settings. Clinicians should consider such observations when making treatment decisions, particularly for patients with comorbid sleep disorders.
MeSH term(s)	Anticonvulsants/pharmacology ; Anticonvulsants/therapeutic use ; Disorders of Excessive Somnolence/drug therapy ; Epilepsy/complications ; Epilepsy/drug therapy ; Humans ; Lamotrigine/pharmacology ; Lamotrigine/therapeutic use ; Sleep
Chemical Substances	Anticonvulsants ; Lamotrigine (U3H27498KS)
Language	English
Publishing date	2021-10-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1414211-9
ISSN	1532-2955 ; 1087-0792
ISSN (online)	1532-2955
ISSN	1087-0792
DOI	10.1016/j.smrv.2021.101559
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Article ; Online: PAP use in mild cognitive impairment to delay progression to dementia.

Maestri, Michelangelo / Liguori, Claudio / Bonanni, Enrica / Guarnieri, Biancamaria

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine

2020 Volume 16, Issue 8, Page(s) 1397

MeSH term(s)	Cognitive Dysfunction ; Dementia/complications ; Disease Progression ; Humans
Language	English
Publishing date	2020-04-24
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2397213-0
ISSN	1550-9397 ; 1550-9389
ISSN (online)	1550-9397
ISSN	1550-9389
DOI	10.5664/jcsm.8536
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