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Abstract Background Sarcopenia is an age-related clinical syndrome characterized by the progressive loss of muscle mass and muscle strength. It appears to be closely linked to dementia, particularly Alzheimer’s disease (AD); however, its prevalence among AD patients remains unclear. In this study, we assessed differences in sarcopenia prevalence between non-demented individuals and AD patients. Moreover, we assessed sex-specific differences in sarcopenia prevalence and explored the diagnostic value of the Muscle Quality Index (MQI) for diagnosing sarcopenia among AD patients. Method Cross-sectional study including 145 patients with probable AD and 51 older adults with normal cognition. Sarcopenia was diagnosed according to the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP1 and EWGSOP2) and of the Foundation for the National Institutes of Health (FNIH). The MQI was computed as the ratio of handgrip strength to skeletal muscle mass. Results No significant difference in sarcopenia prevalence was observed between AD patients and controls. Prevalence ranged from 3.4 to 23.4% in AD patients and from 2 to 11.8% in controls, depending on diagnostic criteria. Prevalence was higher using EWGSOP1 and decreased using EWGSOP2 and FNIH. Prevalence was higher in males than in females with AD. The MQI was lower in AD patients than in controls (95%CI: − 0.23, − 0.05, p

BackgroundSplit phenomena (SP) are characterized by patterns of differential muscle wasting and atrophy, which are highly prevalent in amyotrophic lateral sclerosis (ALS) patients. Several neurophysiological indicators, including the split-hand index (SHI), split-leg index (SLI), and split-elbow index (SEI), have been proposed to assess SP. Nevertheless, their cutoff values and the impact of age and sex on these measures remain unclear.MethodsWe prospectively collected neurophysiological data from 300 healthy adult subjects. The following indices were measured from compound muscle action potentials (CMAPs): SHI [abductor pollicis brevis (APBcmap) x first dorsal interosseous (FDI)cmap/adductor digiti minimi (ADMcmap)], SEI (BICEPScmap/TRICEPScmap), SLI (extensor digit brevis (EDB)cmap/abductor Hallucis (AH)cmap), and the neurophysiological ratios APBcmap /ADMcmap and FDIcmap/ADMcmap. Multiple linear regression analysis was used to investigate the association between age, sex, CMAPs, and neurophysiological indicators.ResultsThe median SHI was 10.4, with a median APBcmap/ADMcmap ratio of 0.9 and a median FDIcmap/ADMcmap ratio of 1.2. The median SEI was 1.6 (IQR:1.1–2.4) and the median SLI was 0.7 (IQR:0.5–1.0). Negative associations were observed between age, most of the CMAPs, and all the neurophysiological indices, except for SLI. The male subjects exhibited significantly higher CMAP values for the first dorsal interosseous (FDI), biceps, and SHI compared to the female participants.ConclusionOur findings highlight the importance of age- and sex-adjusted normative data for SP indices, which could enhance their diagnostic accuracy and clinical utility in patients with ALS. The SL index appears to be the most reliable indicator, as it showed no significant association with age or sex.

Abstract Objective In Alzheimer's disease (AD), the presence of circadian dysfunction is well‐known and may occur early in the disease course. The melanopsin retinal ganglion cell (mRGC) system may play a relevant role in contributing to circadian dysfunction. In this study, we aimed at evaluating, through a multimodal approach, the mRGC system in AD at an early stage of disease. Methods We included 29 mild–moderate AD (70.9 ± 11 years) and 26 (70.5 ± 8 years) control subjects. We performed an extensive neurophtalmological evaluation including optical coherence tomography with ganglion cell layer segmentation, actigraphic evaluation of the rest‐activity rhythm, chromatic pupillometry analyzed with a new data‐fitting approach, and brain functional MRI combined with light stimuli assessing the mRGC system. Results We demonstrated a significant thinning of the infero‐temporal sector of the ganglion cell layer in AD compared to controls. Moreover, we documented by actigraphy the presence of a circadian‐impaired AD subgroup. Overall, circadian measurements worsened by age. Chromatic pupillometry evaluation highlighted the presence of a pupil‐light response reduction in the rod condition pointing to mRGC dendropathy. Finally, brain fMRI showed a reduced occipital cortex activation with blue light particularly for the sustained responses. Interpretation Overall, the results of this multimodal innovative approach clearly document a dysfunctional mRGC system at early stages of disease as a relevant contributing factor for circadian impairment in AD providing also support to the use of light therapy in AD.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects both motor and non-motor functions, including sleep regulation. Emerging evidence suggests that the hypothalamus, a brain region that plays a critical role in sleep-wake regulation, may be involved in the pathogenesis of ALS-related sleep disturbances. In this review, we have summarized results of studies on sleep disorders in ALS published between 2000 and 2023. Thereafter, we examined possible mechanisms by which hypothalamic dysfunctions may contribute to ALS-related sleep disturbances. Achieving a deeper understanding of the relationship between hypothalamic dysfunction and sleep disturbances in ALS can help improve the overall management of ALS and reduce the burden on patients and their families.

Abstract Background The 3-item SARC-F (SARC-F-3) and the 5-item Mini Sarcopenia Risk Assessment (MSRA-5) questionnaires have been recently proposed to screen elderly people regarding the risk of sarcopenia. However, no studies have investigated their performances in Alzheimer’s disease (AD). Methods We conducted a single-center observational study, including 130 consecutive AD patients (mean age: 70.71 ± 8.50 y, 54.6% women) who attended a center for neurodegenerative diseases. Sarcopenia was diagnosed using the European Working Group on Sarcopenia in Older People of 2010 (EWGSOP1) and of 2018 (EWGSOP2) criteria. Sensitivity, specificity, positive and negative likelihood ratio, and the area under the receiver operating characteristic curve (AUC) were used to assess the diagnostic performance of SARC-F-3 and MSRA-5. Results SARC-F-3 showed a sensitivity of 9.7%, a specificity of 82.8% and an AUC of 0.41 using EWGSOP1, whereas the sensitivity was of 16.7%, specificity of 84.7% and AUC of 0.58 using EWGSOP2. The MSRA-5 displayed a sensitivity of 3.2%, a specificity of 89.9% and an AUC of 0.41 using EWGSOP1, whereas sensitivity was of 0%, specificity of 91.1% and the AUC of 0.55 using EWGSOP2 criteria. The questionnaires showed a moderate agreement (Cohen's k = 0.53). Conclusions In our sample of AD patients, a sizable number of sarcopenic individuals were misidentified by SARC-F-3 and MSRA-5, making those questionnaires unsuitable for sarcopenia screening. Considering that sarcopenia has a high prevalence in dementia and that its correct and timely identification is paramount for optimal management of patients, the development and validation of an ad-hoc sarcopenia screening tool for AD patients is highly desirable.

Abstract Background Currently, there is a lack of knowledge concerning where the pathological process starts and how the neurodegeneration spreads during the course of amyotrophic lateral sclerosis (ALS). Aims This study aims to evaluate the spreading direction of the disease and the corresponding clinical characteristics in a cohort of patients with limb‐onset ALS. Patients and methods Consecutive incident ALS patients referring to an ALS tertiary center from Southern Italy, between 2015 and 2021, were recruited in the study. According to the initial directions of spread, patients were dichotomized into horizontal spreading pattern (HSP) or vertical spreading pattern (VSP) groups. Results Among 137 newly diagnosed ALS, 87 presented a spinal onset. Ten patients with pure LMN were not included in the study. All cases reported a clear spread direction. The frequency of HSP and VSP spreading was similar overall (47 vs. 30). The prevalence of HSP was higher (74% vs. 50%) in patients with upper limb‐onset (UL‐ALS), compared to patients with lower limb‐onset (LL‐ALS; p < .05). Conversely, the occurrence of VSP spread was threefold higher in patients with LL‐ALS, compared to UL‐ALS (p < .05). Patients with VSP showed a wider upper motor neuron impairment, whereas the involvement of LMN resulted greater in patients with HSP. Patients with HSP exhibited a greater drop of ALSFRS‐r sub‐score in the region of onset, while VSP showed a slighter but more diffuse reduction of ASLFRS‐r subscore in more body districts beyond the site of onset. Patients with VSP were also characterized by a higher median progression rate and an earlier median bulbar involvement, compared to HSP. Conclusions Our findings suggested investigating the spreading direction of ALS among patients with spinal onset, to better delineate the clinical profiles of patients with ALS, and predict an earlier impairment of bulbar muscle and a more rapid progression of the disease

IntroductionPrimary Progressive Aphasia (PPA) is a neurological disease characterized by linguistic deficits. Semantic (svPPA) and non-fluent/agrammatic (nfvPPA) variants are the two main clinical subtypes. We applied a novel analytical framework, based on radiomic analysis, to investigate White Matter (WM) asymmetry and to examine whether asymmetry is associated with verbal fluency performance.MethodsAnalyses were performed on T1-weighted images including 56 patients with PPA (31 svPPA and 25 nfvPPA) and 53 age- and sex-matched controls. Asymmetry Index (AI) was computed for 86 radiomics features in 34 white matter regions. The relationships between AI, verbal fluency performance (semantic and phonemic) and Boston Naming Test score (BNT) were explored through Spearman correlation analysis.ResultsRelative to controls, WM asymmetry in svPPA patients involved regions adjacent to middle temporal cortex as part of the inferior longitudinal (ILF), fronto-occipital (IFOF) and superior longitudinal fasciculi. Conversely, nfvPPA patients showed an asymmetry of WM in lateral occipital regions (ILF/IFOF). A higher lateralization involving IFOF, cingulum and forceps minor was found in nfvPPA compared to svPPA patients. In nfvPPA patients, semantic fluency was positively correlated to asymmetry in ILF/IFOF tracts. Performances at BNT were associated with AI values of the middle temporal (ILF/SLF) and parahippocampal (ILF/IFOF) gyri in svPPA patients.DiscussionRadiomics features depicted distinct pathways of asymmetry in svPPA and nfvPPA involving damage of principal fiber tracts associated with speech and language. Assessing asymmetry of radiomics in PPA allows achieving a deeper insight into the neuroanatomical damage and may represent a candidate severity marker for language impairments in PPA patients.

Abstract Background The clinical diagnosis of behavioral variant frontotemporal dementia (bvFTD) in patients with a history of primary psychiatric disorder (PPD) is challenging. PPD shows the typical cognitive impairments observed in patients with bvFTD. Therefore, the correct identification of bvFTD onset in patients with a lifetime history of PPD is pivotal for an optimal management. Methods Twenty‐nine patients with PPD were included in this study. After clinical and neuropsychological evaluations, 16 patients with PPD were clinically classified as bvFTD (PPD‐bvFTD+), while in 13 cases clinical symptoms were associated with the typical course of the psychiatric disorder itself (PPD‐bvFTD–). Voxel‐ and surface‐based investigations were used to characterize gray matter changes. Volumetric and cortical thickness measures were used to predict the clinical diagnosis at a single‐subject level using a support vector machine (SVM) classification framework. Finally, we compared classification performances of magnetic resonance imaging (MRI) data with automatic visual rating scale of frontal and temporal atrophy. Results PPD‐bvFTD+ showed a gray matter decrease in thalamus, hippocampus, temporal pole, lingual, occipital, and superior frontal gyri compared to PPD‐bvFTD– (p

Background: Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of upper (UMN) and lower motor neurons (LMN) in four different body regions (bulbar, cervical, thoracic, and lumbosacral). Over the past decades, several clinical scoring systems have been developed to assess the UMN and LMN burden in ALS. However, concerning the bulbar LMN burden, the available scoring systems solely assess the presence/absence of bulbar LMN signs without providing a degree of impairment. Therefore, in this study, we proposed a novel scale to stratify subjects with ALS according to the bulbar LMN involvement and assessed its prognostic value. Methods: We developed a four-item scale based on the LMN signs according to the El Escorial criteria. Ten raters, specializing in ALS or neurocognitive disorders, retrospectively applied the scale to the first evaluation of 195 patients with ALS. Cohen’s kappa (Cohen’s k) and an intra-class correlation coefficient (ICC) were used to assess the inter-rater reliability. The Kaplan–Mayer estimator was used to estimate survival distribution according to the bulbar scale scores. Results: The raters showed a substantial to excellent agreement with Cohen’s k, ranging from 0.834 to 0.975, with an overall ICC of 0.922 (95% CI = 0.906–0.936). The survival distribution was statistically different across the three bulbar scale scores (χ2(2) = 9.50, p < 0.01). Conclusions: Our bulbar LMN scale represents a reliable measure of the bulbar LMN signs in ALS. This easy-to-administer clinical scale could provide unique information in phenotyping and predicting survival in ALS.

Alzheimer’s disease (AD) is characterized by reduced fast brain oscillations in the gamma band (γ, > 30 Hz). Several animal studies show that inducing gamma oscillations through (multi)sensory stimulation at 40 Hz has the potential to impact AD-related cognitive decline and neuropathological processes, including amyloid plaques deposition, neurofibrillary tangles formation, and neuronal and synaptic loss. Therefore Gamma Entrainment Using Sensory stimulation (GENUS) is among the most promising approaches for AD patients’ treatment. This review summarizes the evidence on GENUS effectiveness, from animal models to AD patients. Despite the application on human is in its infancy, the available findings suggest its feasibility for the treatment of AD. We discuss such results in light of parameter improvement and possible underlying mechanisms. We finally emphasize the need for further research for its development as a disease-modifying non-pharmacological intervention.

Frontotemporal dementia (FTD) is a spectrum of clinical syndromes that affects personality, behavior, language, and cognition. The current diagnostic criteria recognize three main clinical subtypes: the behavioral variant of FTD (bvFTD), the semantic variant of primary progressive aphasia (svPPA), and the non-fluent/agrammatic variant of PPA (nfvPPA). Patients with FTD display heterogeneous clinical and neuropsychological features that highly overlap with those presented by psychiatric syndromes and other types of dementia. Moreover, up to now there are no reliable disease biomarkers, which makes the diagnosis of FTD particularly challenging. To overcome this issue, different studies have adopted metrics derived from magnetic resonance imaging (MRI) to characterize structural and functional brain abnormalities. Within this field, a growing body of scientific literature has shown that graph theory analysis applied to MRI data displays unique potentialities in unveiling brain network abnormalities of FTD subtypes. Here, we provide a critical overview of studies that adopted graph theory to examine the topological changes of large-scale brain networks in FTD. Moreover, we also discuss the possible role of information arising from brain network organization in the diagnostic algorithm of FTD-spectrum disorders and in investigating the neural correlates of clinical symptoms and cognitive deficits experienced by patients.

Radiomics has been proposed as a useful approach to extrapolate novel morphological and textural information from brain Magnetic resonance images (MRI). Radiomics analysis has shown unique potential in the diagnostic work-up and in the follow-up of patients suffering from neurodegenerative diseases. However, the potentiality of this technique in distinguishing frontotemporal dementia (FTD) subtypes has so far not been investigated. In this study, we explored the usefulness of radiomic features in differentiating FTD subtypes, namely, the behavioral variant of FTD (bvFTD), the non-fluent and/or agrammatic (PNFA) and semantic (svPPA) variants of a primary progressive aphasia (PPA). Classification analyses were performed on 3 Tesla T1-weighted images obtained from the Frontotemporal Lobar Degeneration Neuroimaging Initiative. We included 49 patients with bvFTD, 25 patients with PNFA, 34 patients with svPPA, and 60 healthy controls. Texture analyses were conducted to define the first-order statistic and textural features in cortical and subcortical brain regions. Recursive feature elimination was used to select the radiomics signature for each pairwise comparison followed by a classification framework based on a support vector machine. Finally, 10-fold cross-validation was used to assess classification performances. The radiomics-based approach successfully identified the brain regions typically involved in each FTD subtype, achieving a mean accuracy of more than 80% in distinguishing between patient groups. Note mentioning is that radiomics features extracted in the left temporal regions allowed achieving an accuracy of 91 and 94% in distinguishing patients with svPPA from those with PNFA and bvFTD, respectively. Radiomics features show excellent classification performances in distinguishing FTD subtypes, supporting the clinical usefulness of this approach in the diagnostic work-up of FTD.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive cognitive decline, mostly prominent in the domain of memory, but also associated with other cognitive deficits and non-cognitive symptoms. Reduced muscle strength is common in AD. However, the current understanding of its relationship with cognitive decline is limited. This study investigates the relationship between muscle strength and cognition in patients with AD and mild cognitive impairment (MCI). We enrolled 148 consecutive subjects, including 74 patients with probable AD dementia, 37 MCI, and 37 controls. Participants underwent neuropsychological evaluation focused on attention, working memory, declarative memory and learning. Muscle strength and muscle mass were measured through hand dynamometer and bio-electrical impedance analysis, respectively. Patients with AD dementia were divided with respect to the severity of cognitive impairment into mild and moderate-to-severe patients. Moderate-to-severe patients with AD presented lower handgrip strength than MCI and controls. No differences were observed in muscle mass. In MCI and AD dementia, handgrip strength was associated with overall cognitive functioning, attentional and memory performance. The routine implementation of handgrip strength assessment in the clinical work-up of patients with MCI and AD could potentially represent a simple method to monitor functional and cognitive decline along the disease course.

Delusions are part of the neuropsychiatric symptoms that patients suffering from neurodegenerative conditions frequently develop at some point of the disease course and are associated with an increased risk of cognitive and functional decline. Delirium is a syndrome characterized by acute onset of deficits in attention, awareness, and cognition that fluctuate in severity over a short time period. Delusions and delirium are frequently observed in the context of neurodegeneration, and their presence can easily mislead clinicians toward a misdiagnosis of psychiatric disorder further delaying the proper treatment. Risk factors for developing delusion and delirium in neurodegenerative conditions have been investigated separately while the possible interplay between these two conditions has not been explored so far. With this study, we aim to achieve a more comprehensive picture of the relationship between delusions and delirium in neurodegeneration by analyzing prevalence and subtypes of delusions in different neurodegenerative disorders; providing an overview of clinical tools to assess delusions in neurodegenerative patients and how delusions are covered by delirium assessment tools and discussing the possible common pathophysiology mechanisms between delusion and delirium in neurodegenerative patients. A more extensive characterization of the relationship between delusions and delirium may help to understand whether delusions may constitute a risk factor for delirium and may ameliorate the management of both conditions in patients with neurodegenerative disorders.

Abstract To search for discriminating biomarkers, 30 patients with idiopathic rapid‐eye‐movements sleep behavior disorder (iRBD) were compared with 17 patients with RBD within narcolepsy type 1. Both groups underwent extensive examinations, including skin biopsy searching for phosphorylated α‐synuclein deposits and whole‐night video‐polysomnography. Skin biopsy was positive for phosphorylated α‐synuclein deposits in 86.7% of iRBD patients and in none of narcoleptic patients. The analysis of video‐polysomnographic motor events showed differences in their occurrence throughout the night in the two groups. iRBD and RBD due to narcolepsy do have different clinical and pathological findings, confirming a different pathophysiology.

Narcolepsy type 1 (NT1) deeply impacts on quality of life, especially during adolescence, with NT1 children and adolescents that frequently report difficulties in integration with peers and decreased participation in after-school activities. Here we describe the case of NT1 teenager girl presenting with severe physical and social withdrawal, fulfilling the proposed diagnostic criteria for hikikomori, together with the classic NT1 symptoms. Social withdrawal is an overlooked phenomenon among NT1 children and adolescents that, if present, require a multidisciplinary approach and personalized interventions, but patients can benefit from NT1 pharmacological treatment.

Abstract Study Objectives Narcolepsy type 1 (NT1) is a chronic rare hypersomnia of central origin requiring a combination of behavioral and pharmacological treatments. During the coronavirus disease 2019 (COVID‐19) pandemic, in Italy the population was forced into a lockdown. With this study, we aimed to describe the lockdown impact on NT1 symptom management, according to different patients' working schedule. Methods In the period between 10 April and 15 May 2020, we performed routine follow‐up visits by telephone (as recommended during the COVID‐19 emergency) to 50 patients >18 years old (40% males) under stable long‐term treatment. We divided patients into three groups: unchanged working schedule, forced working/studying at home, and those who lost their job (“lost occupation”). Current sleep–wake habit and symptom severity were compared with prelockdown assessment (six months before) in the three patient groups. Results At assessment, 20, 22, and eight patients belonged to the unchanged, working/studying at home, and lost occupation groups, respectively. While in the lost occupation group, there were no significant differences compared with prepandemic assessment, the patients with unchanged schedules reported more nocturnal awakenings, and NT1 patients working/studying at home showed an extension of nocturnal sleep time, more frequent daytime napping, improvement of daytime sleepiness, and a significant increase in their body mass index. Sleep‐related paralysis/hallucinations, automatic behaviors, cataplexy, and disturbed nocturnal sleep did not differ. Conclusions Narcolepsy type 1 patients working/studying at home intensified behavioral interventions (increased nocturnal sleep time and daytime napping) and ameliorated daytime sleepiness despite presenting with a slight, but significant, increase of weight.

We investigated the association between the Magnetic Resonance Parkinsonism Index (MRPI) and REM sleep behavior disorder (RBD). We included 226 de novo PD patients (82 PD-RBD and 144 PD-noRBD) and 19 idiopathic RBD patients. Furthermore, 3T T1-weighted MR images were used for automated brainstem calculations. MRPI values were higher in the PD-RBD (p = 0.004) compared to PD-noRBD patients. Moreover, MRPI proved to be a significant predictor of REM Behavior Disorder Screening Questionnaire scores in PD (β = 0.195, p = 0.007) and iRBD patients (β = 0.582, p = 0.003). MRPI can be used as an imaging marker of RBD in patients with de novo PD and iRBD.

Sleep paralysis (SP) is a condition where a person is paralyzed upon waking or falling asleep. SP afflicts ~20% of people, and is also one of the typical symptoms in narcolepsy. During SP the sleeper may experience hallucinations. Unsurprisingly, SP is associated with great fear globally. To date, there are no published clinical trials or outcome data for treating this condition. However, few non-pharmacological interventions have been proposed, including cognitive behavioral approaches, and case studies showing clinical amelioration with auto-hypnosis and Meditation-Relaxation (MR) therapy. The latter for instance showed positive preliminary results; when applied for 8 weeks it reduced SP frequency and anxiety/worry symptoms. With this paper we aimed to evaluate, with a small-scale pilot study, the efficacy of MR therapy for SP in patients with narcolepsy. Ten patients with narcolepsy and SP were enrolled in the study. Notably, MR therapy (n = 6), applied for 8 weeks, resulted in a dramatic decrease in the number of days SP occurred (50% reduction); and the total number of SP episodes (54% reduction) in the last month of the study (demonstrated by large within-group effect sizes); unlike the control intervention (deep breathing) (n = 4). These findings are preliminary and exploratory given the small sample. Nonetheless, they represent the first proof of concept at providing empirically-guided insights into the possible efficacy of a novel treatment for frequently occurring SP. Although the study was conducted in patients with narcolepsy we cautiously suggest that the findings may generalize to individuals with isolated SP.

IntroductionNarcolepsy type 1 (NT1) is a chronic and rare sleep disorder typically arising during adolescence and young adulthood. The main symptoms are excessive daytime sleepiness and cataplexy, a prototypical fall down elicited by huge emotions. Social relationships, school, work, and general health perception are frequently impaired in patients, who often show lower quality-of-life scores. We report which management strategies a young patient (DMG) adopted to cope with NT1 during his growth, avoiding exhibiting serious impairments to his global functioning.MethodsA clinical psychologist explores the history of the patient’s disease and the self-acquired strategies used to cope with the symptoms. The patient’s global adaptation to the disease, stress-related managing skills, and overall well-being are assessed by standardized scales [Illness Behavior Questionnaire (IBQ); Coping Orientations to Problems Experienced (COPE); and Psychological General Well-Being Index (PGWBI)]. We conducted a qualitative analysis of the patient’s narration of his illness according to the procedure of the Grounded Theory. The MAXQDA software program was used to code the verbatim transcript.ResultsFrom the qualitative analysis of the interview, three thematic cores emerged: 1) the disease history; 2) the patient’s friendship with AD, a friend of his age diagnosed with NT1 since childhood; 3) the strategies used to deal with his symptoms before the diagnosis of NT1 and the related treatment. From the psychometric tests, the patient presents good coping strategies in dealing with stressful problems and events based mainly on acceptance and positive reinterpretation of the stressful situation.ConclusionThis case shows that comparing peers of the same age and suffering from the same illness improve the patient’s self-management ability to cope and live well with NT1.

Objectives: Regular physical activity is routinely recommended in children and adolescents suffering from narcolepsy type 1 (NT1), but controlled studies analyzing its influence on sleep/wake behavior, metabolic, and anthropometric profile in pediatric NT1 are lacking.Methods: Fifty consecutive drug-naïve NT1 children and adolescents were assessed through actigraphic, clinical, and metabolic evaluations. Patients were compared with respect to their engagement in leisure-time physical activities (LTPA): patients engaged in LTPA (n = 30) and patients not engaged (No-LTPA, n = 20), respectively.Results: LTPA patients presented lower BMI, with different BMI categories distribution and higher HDL cholesterol, when compared with No-LTPA subjects. Increased night-sleep duration, higher sleep quality, and reduction of nap frequency were documented through actigraphy in LTPA subjects. Subjective sleepiness, as measured by ESS-CHAD, was also lower in LTPA subjects while cataplexy frequency proved similar between the two groups.Discussion: In pediatric NT1 patients, regular engagement in LTPA is associated with significant differences on sleepiness, anthropometric and metabolic profile and objectively assessed sleep/wake behavior. Engagement in LTPA is beneficial and should be strongly encouraged in pediatric NT1 patients.

Attentional complaints are common in narcolepsy patients and can overlap with daytime sleepiness features. Few studies attempted to characterize attentional domains in narcolepsy leading to controversial results. We aimed to assess the impact of hypocretin deficiency on attentional functioning by comparing performances on the attention network test (ANT) of narcoleptic patients with hypocretin deficiency (narcolepsy type 1-NT1) versus patients without hypocretin deficiency (narcolepsy type 2-NT2) and healthy controls. We also addressed frequency and severity of psychopathological symptoms and their influence on performances on ANT.Twenty-one NT1 patients, fifteen NT2 patients and twenty-two healthy controls underwent the ANT, which allows assessing three separate attentional processes (alerting, orienting and executive control), and a psychometric assessment including questionnaires on attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, anxiety and depression symptoms.NT1 and NT2 patients presented with slower reaction times compared to controls. NT1 patients exhibited an impairment of alerting network relative to NT2 and healthy controls, while orienting and executive control networks efficiency were comparable between groups. NT1 and NT2 displayed higher severity of ADHD inattentive domain than controls, NT1 patients also displayed higher severity of ADHD hyperactive domain and depressive symptoms. In NT1, ADHD and depressive symptoms were positively correlated.Despite a shared slowing of reaction times in both NT1 and NT2, a selective impairment of alerting network was present only in hypocretin deficient patients. Clinicians should carefully consider attentional deficits and psychopathological symptoms, including ADHD symptoms, in the clinical assessment and management of patients with narcolepsy.