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Background: Idiopathic rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of cit-synucleinopathies. Reliable biomarkers are needed to predict phenoconversion.Objective: The aim was to derive and validate a brain glucose metabolism pattern related to phenoconversion in iRBD (iRBDconvRP) using spatial covariance analysis (Scaled Subprofile Model and Principal Component Analysis [SSM-PCA]).Methods: Seventy-six consecutive iRBD patients (70 +/- 6 years, 15 women) were enrolled in two centers and prospectively evaluated to assess phenoconversion (30 converters, 73 +/- 6 years, 14 Parkinson's disease and 16 dementia with Lewy bodies, follow-up time: 21 +/- 14 months; 46 nonconverters, 69 +/- 6 years, follow-up time: 33 +/- 19 months). All patients underwent [F-18]FDG-PET (F-18-fluorodeoxyglucose positron emitting tomography) to investigate brain glucose metabolism at baseline. SSM-PCA was applied to obtain the iRBDconvRP; nonconverter patients were considered as the reference group. Survival analysis and Cox regression were applied to explore prediction power.Results: First, we derived and validated two distinct center-specific iRBDconvRP that were comparable and significantly able to predict phenoconversion. Then, SSM-PCA was applied to the whole set, identifying the iRBDconvRP. The iRBDconvRP included positive voxel weights in cerebellum; brainstem; anterior cingulate cortex; lentiform nucleus; and middle, mesial temporal, and postcentral areas. Negative voxel weights were found in posterior cingulate, precuneus, middle frontal gyrus, and parietal areas. Receiver operating characteristic analysis showed an area under the curve of 0.85 (sensitivity: 87%, specificity: 72%), discriminating converters from nonconverters. The iRBDconvRP significantly predicted phenoconversion (hazard ratio: 7.42, 95% confidence interval: 2.6-21.4).Conclusions: We derived and validated an iRBDconvRP to efficiently discriminate converter from nonconverter iRBD patients. [F-18]FDG-PET pattern analysis has potential as a phenoconversion biomarker in iRBD patients. (C) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Parkinson’s disease (PD) is characterized by motor symptoms often experienced in concomitance with non-motor symptoms (NMS), such as depression, apathy, pain, sleep disorders, and urinary dysfunction. The present study aimed to explore the effect of safinamide treatment on NMS and quality of life in motor-fluctuating PD patients. VALE-SAFI is an observational single-centre study performed in fluctuating PD patients starting safinamide treatment and followed for 6 months. The effects of safinamide on NMS, sleep, fatigue, depression and pain were assessed through validated sales. Changes in the scales from baseline to the 6-month follow-up visit were analysed. 60 PD patients (66.67% males) were enrolled at baseline, and 45 patients completed the 6-month follow-up. PD patients improved motor symptoms at follow-up, with the significant reduction of motor fluctuations. The global score of the NMS Scale significantly decreased between baseline and the follow-up. Regarding pain domains, patients reported a significant improvement in discolouration and oedema/swelling. Further, a significant improvement was observed from baseline to follow-up in sleep quality measured through the Pittsburgh Sleep Quality Index, while no changes were documented in daytime sleepiness. No differences were found in depression and fatigue between baseline and follow-up. Finally, the patient’s perception of the impact of PD on functioning and well-being decreased from baseline to follow-up. The present findings confirmed the beneficial effect of safinamide on both motor and non-motor symptoms, also improving the quality of life of PD patients. Furthermore, these data support the positive effects of safinamide on pain and mood, as well as on sleep quality and continuity.

Non-sleep symptoms, as depression, anxiety and overweight, are often encountered in narcoleptic patients. The purposes of this study are to evaluate mood, impulsiveness, emotion, alexithymia, and eating behavior in patients with narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2) compared to healthy controls and to investigate possible correlations between clinical-demographic data, polysomnographic parameters, and subjective questionnaires. Consecutive patients affected by NT1 and NT2 underwent to Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 Scale, Barratt Impulsivity Scale-11, Difficulties in Emotion Regulation Scale, Toronto Alexithymia Scale, and Eating Disorder Evaluation Questionnaire. Daytime sleepiness was assessed using Epworth sleepiness score. Data were compared with controls. Fourteen NT1, 10 NT2, and 24 healthy subjects were enrolled. Toronto Alexithymia Scale total score was significantly higher in NT1 than NT2. Compared to controls, NT1 patients exhibited significantly higher scores at Patient Health Questionnaire-9 and Difficulties in Emotion Regulation Scale. A positive correlation between hypnagogic hallucinations and Difficulties in emotion regulation was found. NT1 and NT2 share several psycho-emotional aspects, but whereas NT1 patients exhibit more depressive mood and emotion dysregulation compared to controls, alexithymic symptoms are more prominent in NT1 than NT2. Hypnagogic hallucinations, emotion dysregulation, and alexithymia appear to be correlated, supporting the hypothesis of mutual interaction of the above areas in narcolepsy.

Abstract Background A brain glucose metabolism pattern related to phenoconversion in patients with idiopathic/isolated REM sleep behaviour disorder (iRBDconvRP) was recently identified. However, the validation of the iRBDconvRP in an external, independent group of iRBD patients is needed to verify the reproducibility of such pattern, so to increase its importance in clinical and research settings. The aim of this work was to validate the iRBDconvRP in an independent group of iRBD patients. Methods Forty iRBD patients (70 ± 5.59 years, 19 females) underwent brain [18F]FDG-PET in Seoul National University. Thirteen patients phenoconverted at follow-up (7 Parkinson disease, 5 Dementia with Lewy bodies, 1 Multiple system atrophy; follow-up time 35 ± 20.56 months) and 27 patients were still free from parkinsonism/dementia after 62 ± 29.49 months from baseline. We applied the previously identified iRBDconvRP to validate its phenoconversion prediction power. Results The iRBDconvRP significantly discriminated converters from non-converters iRBD patients (p = 0.016; Area under the Curve 0.74, Sensitivity 0.69, Specificity 0.78), and it significantly predicted phenoconversion (Hazard ratio 4.26, C.I.95%: 1.18–15.39). Conclusions The iRBDconvRP confirmed its robustness in predicting phenoconversion in an independent group of iRBD patients, suggesting its potential role as a stratification biomarker for disease-modifying trials.

Introduction Early -onset Parkinson’s disease (EOPD) labels those cases with onset earlier than fifty. Although peculiarities emerged either in clinical or pathological features, EOPD is managed alike typical, late-onset PD. A customized approach would be, instead, better appropriate. Accordingly, a deeper characterization of the clinical course, with an estimation of the disease progression rate, the therapy flow, and the main motor and non-motor complications occurrence, is needed. Methods A longitudinal cohort of 193 EOPD patients (selected on a single-centre population of 2000 PD cases) was retrospectively analysed, providing descriptive statics on a series of clinical parameters (genetics, phenotype, comorbidities, therapies, motor and non-motor complications, marital and gender issues) and modelling the trajectories from diagnosis to 10 years later of both Hoehn and Yahr (H&Y) stage and levodopa equivalent daily dose (LEDD). Results EOPD had a prevalence of 9.7%, including few monogenic cases. It mostly appeared as a motor syndrome, with asymmetric, rigid-akinetic presentation. H&Y linearly progressed with an increment of 0.92 points/10 years; LEDD flow had a non-linear trend, increasing of 526.90 mg/day in 0–5 years, and 166.83 mg/day in 5–10 years. Motor fluctuations started 6.5 ± 3.2 years from onset, affecting up to 80% of the cohort. Neuropsychiatric troubles interested the 50%, sexual complaints the 12%. Gender-specific motor disturbances emerged. Conclusion We shaped EOPD course, modelling a “brain-first” PD subtype, slowly progressive, with non-linear dopaminergic requirement. Major burden mostly resulted from motor fluctuations, neuropsychiatric complications, sexual and marital complaints, with a considerable gender-effect.

Introduction: Parkinson’s disease (PD) is a multisystem disease, involving several brain structures. fMRI studies reported abnormal functional connectivity (FC) in PD. EEG is an accessible method to evaluate cortical activity, which may be used to estimate FC. For this aim, we analyzed differences in FC between patients at early stages of PD and healthy controls (HC) using high-density EEG (HD-EEG). Methods: We enrolled 20 early-stage PD patients and 19 age-matched HC. Data were recorded with a 64-channels HD-EEG system. A source-reconstruction method was used to identify brain-region activity. FC was calculated using a weighted phase-lag index in θ-α-β bands. Network-based statistic was used to compare FC between PD and HC. Results: No statistical-significant differences were observed in spectral analysis between groups. PD patients showed a hypoconnected network in α-band primarily composed by frontal lobe, associated with a hyperconnected network in β band, including frontal, sensorimotor, limbic and temporal areas. Moreover, correlation between β FC in sensorimotor areas and PD motor impairment was found (r = 0.80, p = 0.003). Conclusion: HD-EEG revealed FC alterations since early stages of PD, as a tool complementary to fMRI, and it could be a useful early or even preclinical diagnostic marker of disease.

Non-motor symptoms (NMS) characterize the Parkinson’s disease (PD) clinical picture, and as well as motor fluctuations, PD patients can also experience NMS fluctuations (NMF). The aim of this observational study was to investigate the presence of NMS and NMF in patients with PD using the recently validated Non-Motor Fluctuation Assessment questionnaire (NoMoFa) and to evaluate their associations with disease characteristics and motor impairment. Patients with PD were consecutively recruited, and NMS, NMF, motor impairment, motor fluctuations, levodopa-equivalent daily dose, and motor performance were evaluated. One-third of the 25 patients included in the study (10 females, 15 males, mean age: 69.9 ± 10.3) showed NMF, and patients with NMF presented a higher number of NMS (p < 0.01). Static NMS and NoMoFa total score were positively associated with motor performance assessed with the Global Mobility Task (p < 0.01 and p < 0.001), and the latter was also correlated with motor impairment (p < 0.05) but not with motor fluctuations. Overall, this study shows evidence that NMF are frequently reported by mild-to-moderate PD patients and associated with an increased number of NMS. The relationship between NoMoFa total score and motor functioning highlights the importance of understanding the clinical role of NMS and NMF in the management of PD patients.

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 is mostly of central origin but it may coexist with sleep-related breathing disorders. However, there is no consensus on the sleep protocols to be used, assessments vary, and only a minority of patients are regularly tested or are on treatment for EDS. Our study presents data on self-reported and objective EDS in adult-onset myotonic dystrophy type 1. METHODS: Sixty-three patients with adult-onset DM1 were subjected to EDS-sleep assessments (polysomnography, Multiple Sleep Latency Test, Epworth Sleepiness Scale). Correlation coefficients were computed to assess the relationship between sleep and sleepiness test results, fatigue, and quality of life. RESULTS: 33% and 48% of patients had EDS based, respectively, on the Epworth Sleepiness Scale and the Multiple Sleep Latency Test, with a low concordance between these tests (k = 0.19). Thirteen patients (20%) displayed 2 or more sleep-onset rapid eye movement periods on Multiple Sleep Latency Test. Patients having EDS by Multiple Sleep Latency Test had a shorter disease duration (P < .05), higher total sleep time and sleep efficiency and lower wake after sleep onset on polysomnography. Patients with self-reported EDS reported significantly higher fatigue score compared with patients without EDS (P < .05). No other difference was found in demographic, clinical, and respiratory features. CONCLUSIONS: EDS test results are contradictory, making treatment options difficult. Combining quantitative tests and self-reported scales may facilitate physicians in planning EDS care with patients and families. CITATION: Sansone VA, Proserpio P, Mauro L, et al. Assessment of self-reported and objective daytime sleepiness in adult-onset myotonic dystrophy type 1. J Clin Sleep Med. 2021;17(12):2383–2391.

The aim of our study was to evaluate the diagnostic and prognostic value of Electroencephalogram (EEG), brain Magnetic Resonance Imaging (MRI) and cerebrospinal fluid features, currently representing Creutzfeldt-Jacob Disease (CJD) diagnostic criteria.A retrospective study on rapidly progressive dementia patients admitted at the Neurology Clinic of the University of Rome "Tor Vergata" between 2015 and 2020 was conducted. We evaluated clinical, EEG, cerebrospinal fluid and neuroradiological findings.Our analysis included 13 patients with probable CJD and 18 patients with non-CJD rapidly progressive dementia. Periodic sharp wave complexes were observed in 7/13 CJD and in 4/18 non-CJD patients (p =.151). The sub-analysis according to the EEG features revealed that CJD patients with earlier periodic sharp wave complexes had a significantly lower average survival time (p =.003), a shorter time to admission (p =.003) and lower levels of cerebrospinal fluid p-tau (p =.008) compared to CJD patients without periodic sharp wave complexes. Finally, they did not show signs of signal alteration on Fluid Attenuated Inversion Recovery images.Despite the lowest diagnostic specificity and sensibility among the CJD criteria, periodic sharp wave complexes could identify a distinctive phenotype hallmarked by a faster evolution, a reduced survival time and specific MRI and cerebrospinal fluid features.The early presence of the typical EEG pattern may play a prognostic role in CJD.

Antiseizure medications (ASMs) may affect nocturnal sleep and daytime vigilance. Perampanel (PER), a third-generation ASM, showed to improve nocturnal sleep in patients with epilepsy (PWE). Although ASMs can have beneficial effects on nocturnal sleep and daytime sleepiness, no study investigated the effect of PER on both sleep-wake cycle and daytime sleepiness. Therefore, this study aimed to objectively evaluate the sleep-wake cycle and daytime sleepiness in PWE treated with PER as adjunctive therapy.This prospective study included adult PWE who received PER as add-on treatment. Sleep-wake cycle was assessed through actigraphic monitoring and daytime sleepiness by the multiple sleep latency test (MSLT) performed at the end of the actigraphic recording. All patients performed both tests at baseline and at 6-month follow-up.Ten patients (mean age: 44.50 ± 22.71 years, 50.0% female) were included. The mean monthly seizure frequency was 3.20 ± 5.94. Six of ten patients started PER as a first add-on treatment. The final PER dose was 5.11 ± 2.02 mg/day, and nine of ten patients achieved seizure freedom at follow-up. There was a significant decrease in mean monthly seizure frequency from baseline to follow-up (p = 0.004). No significant changes were found in the sleep-wake cycle parameters. An increase in sleep latency mean was observed at MSLT at 6-month follow-up (p = 0.005).This study confirms that adjunctive PER is effective on seizures without pathologically change of the sleep-wake cycle in PWE and can even improve daytime sleepiness. This effect can be mediated by the achievement of seizure control. Therefore, PER may be promising in PWE with sleep disturbances and daytime sleepiness.

Lacosamide (LCM) is a third-generation antiseizure medication (ASM), and its effect on sleep architecture was supported by a few studies in patients with drug-resistant epilepsy in which LCM was used as an add-on treatment. To gather knowledge on ASMs effects on sleep, this study aimed at evaluating the effects of LCM monotherapy on sleep in patients with focal epilepsy. Ten patients diagnosed with epilepsy (mean age 58.00 ± 14.77, 60.0% female, mean monthly seizure frequency 1.20 ± 2.48) starting LCM as monotherapy were included. Sleep architecture was assessed through polysomnography at baseline and at the 6-month follow-up visit. A significant decrease was observed in seizure frequency (p = 0.004), being all patients seizure-free at follow-up. At baseline, eight patients had poor sleep efficiency ( 85%). Sleep efficiency increased at follow-up, with only three patients having an index 85% (p = 0.022). From baseline to follow-up, a significant decrease was observed in sleep latency (p = 0.022) and wakefulness after sleep onset (p = 0.047). Moreover, a significant decrease was observed in the percentage of stage 1 (Md = 6.70 vs Md = 3.85, p = 0.005) and stage 3 (Md = 27.70 vs Md = 22.35, p = 0.01) of Non-REM sleep. This study suggests that LCM monotherapy may positively impact sleep architecture in patients with epilepsy. The sleep efficiency improvement and the decrease of sleep latency and wakefulness after sleep onset observed at follow-up highlight better sleep stability and continuity in patients treated with LCM. Notably, all patients were seizure-free at follow-up, and seizure freedom may also concur to sleep structure improvement.

Mild cognitive impairment (MCI) is frequently diagnosed in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), although the extent of MCI-associated neuropathology has not yet been quantified. The present study compared the differences in neuropsychiatric, neuropsychological, and neuroimaging markers of neurodegeneration in MCI-iRBD and iRBD patients with normal cognition.Sixty-one patients with iRBD were included in the study: 30 patients were included in the MCI subgroup (RBD-MCI) and 31 in the normal cognition subgroup (RBD-NC). Both groups underwent neuropsychiatric and neuropsychological assessments to evaluate psychopathological symptoms and neuropsychological functions. Brain [18F]FDG PET and 123I-FP-CIT-SPECT were performed to evaluate brain glucose metabolism and nigrostriatal dopaminergic function in convenient subgroups of patients, respectively.Neuropsychological measures generally confirmed overall cognitive decline in patients with iRBD-MCI. Immediate long-term verbal memory and visuospatial functions, as well as attentional-executive impairment were evident in the MCI group compared to the NC group. Neuroimaging results indicated reduced brain glucose uptake in the bilateral posterior cingulate cortex and more evident nigrostriatal deafferentation in the RBD-MCI group. There were no differences in psychopathological symptoms between the two groups.This study confirmed that iRBD patients with MCI had a more impaired cognitive status that those with NC. Moreover, the MCI subgroup presented reduced cerebral glucose consumption in brain areas critical for cognition, and a more severe deafferentation of the nigro-striatal regions, highlighting the importance of identifying iRBD patients with MCI for urgent neuroprotective trials.

Non-motor symptoms (NMS) frequently impact health-related quality of life (HRQoL) in patients with Parkinson's Disease (PD). Sleep problems represent one of the main NMS complained by PD patients. In this observation study, sleep problems measured by Parkinson's Disease Sleep Scale - 2nd version (PDSS-2), and HRQoL measured by Parkinson's Disease Questionnaire-39 (PDQ39) were quantified in patients with PD ranging from mild to moderate-advanced disease stages, and correlated to motor impairment and anti-PD therapy.We included idiopathic PD patients who underwent PDSS-2 and PDQ39. Moreover, we assessed patients' motor symptoms by rating the Unified Parkinson's Disease Rating Scale (UPDRS) - III section (motor examination), patients' PD status following HY stage, and levodopa equivalent daily dose (LEDD).One-hundred and fifty-four patients with PD were included and distributed for HY stage. PDSS-2 and PDQ39 total and sub-items scores significantly increased with the HY stage. PDSS-2 total score significantly correlated with PDQ39 total score (γ = 0.63, P 0.01). Finally, distributing PD patients according to the PDSS-2 cut-off for detecting sleep disturbances, we found in poor sleepers (n = 58) higher PDQ39 scores than good sleepers (n = 89).Sleep problems are very common in patients with PD and severely impact on HRQoL. Sleep impairment and low HRQoL occur from the early stages of the disease and deteriorate along disease progression. Further studies investigating sleep and quality of life should be planned for targeting sleep improvement to increase HRQoL and possibly reduce motor impairment.

Introduction Dysregulation of cerebral glucose consumption, alterations in cerebrospinal fluid (CSF) biomarkers, and cognitive impairment have been reported in patients with obstructive sleep apnoea (OSA). On these bases, OSA has been considered a risk factor for Alzheimer’s disease (AD). This study aimed to measure cognitive performance, CSF biomarkers, and cerebral glucose consumption in OSA patients and to evaluate the effects of continuous positive airway pressure (CPAP) treatment on these biomarkers over a 12-month period. Methods Thirty-four OSA patients and 34 controls underwent 18F-fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET), cognitive evaluation, and CSF analysis. A subgroup of 12 OSA patients treated with beneficial CPAP and performing the 12-month follow-up was included in the longitudinal analysis, and cognitive evaluation and 18F-FDG PET were repeated. Results Significantly reduced glucose consumption was observed in the bilateral praecuneus, posterior cingulate cortex, and frontal areas in OSA patients than controls. At baseline, OSA patients also showed lower β-amyloid42 and higher phosphorylated-tau CSF levels than controls. Increased total tau and phosphorylated tau levels correlated with a reduction in brain glucose consumption in a cluster of different brain areas. In the longitudinal analysis, OSA patients showed an improvement in cognition and a global increase in cerebral 18F-FDG uptake. Conclusions Cognitive impairment, reduced cerebral glucose consumption, and alterations in CSF biomarkers were observed in OSA patients, which may reinforce the hypothesis of AD neurodegenerative processes triggered by OSA. Notably, cognition and brain glucose consumption improved after beneficial CPAP treatment. Further studies are needed to evaluate the long-term effects of CPAP treatment on these AD biomarkers.

Epilepsy is increasing, being more common in older adults, with more than 20% of late-onset cases with unknown aetiology (LOEU). Although epilepsy was associated with cognitive impairment, few studies evaluated the trajectories of cognitive decline in patients with LOEU. The present study aimed at assessing biomarkers of Alzheimer's disease (AD) in patients with LOEU and evaluating their cognitive performance for 12 months. For this study, 55 patients diagnosed with LOEU and 21 controls were included. Participants underwent cognitive evaluation and cerebrospinal fluid (CSF) biomarker analysis (ß-amyloid

Introduction Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients’ subgroups based on current drug prescription (drug-naïve patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). Methods We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. Results One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. Conclusion Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach.

Objective Quantitative EEG (qEEG) is an established technique used as objective measure for evaluating the effect of antiseizure medications (ASMs) on EEG background activity and monitoring cognitive effects of ASMs. Perampanel (PER) has been associated with relatively more tolerable cognitive effects in patients with epilepsy. The primary aim of the present study was to verify the effect of PER as first add-on ASM on qEEG in child and adult patients affected by epilepsy. The secondary aim of this study was to verify the effectiveness of the drug as first add-on treatment in both child and adult patients with epilepsy. Methods We collected data from 17 adults and 10 children treated with PER as first add-on treatment, who underwent qEEG analysis before starting PER and at 3-month follow-up under stable treatment. Results PER resulted with significant effectiveness in reducing seizures in both children and adults. Considering qEEG analysis, we observed at follow-up the significant increase in beta1 and beta total bands both in children and adult patients. In particular, children showed the significant increase of beta band frequencies predominantly in the occipital regions, whereas adults showed a widespread increase of beta activity. Moreover, we documented in both child and adult patients the global reduction of delta bands activity. Conclusions This qEEG study documented the relative increase of cortical EEG fast activity in both children and adult patients affected by epilepsy and treated by PER. This result may suggest a potential less negative impact of PER on cognition in patients affected by epilepsy, other than demonstrating effectiveness of the drug when used as first add-on treatment in both children and adult patients.

Introduction The relationship between dyspnea and COVID-19 is unknown. In COVID-19 patients, the higher prevalence of neurological symptoms and the lack of dyspnea may suggest common underlying pathogenetic mechanisms. The aim of this preliminary study is to address whether there is a lack of dyspnea in COVID-19 patients and if there is a relationship between neurological symptoms and the perception of dyspnea. Methods A structured interview regarding the occurrence of subjective neurological symptoms was performed and coupled with a questionnaire about the intensity and qualities of dyspnea. Respiratory rate (RR) and an arterial blood gas on room air were concurrently evaluated. Results Twenty-two patients (age 68.4 ± 13.9 years, 13 males and 9 females) were included and divided into two groups according to the Borg dyspnea scale: dyspneic patients BU ≥ 1(DYSP) and non-dyspneic patients BU

Background Sleep-related symptoms, especially insomnia, are frequently reported by patients with Parkinson’s disease (PD) and can markedly affect motor symptoms and impair patients’ quality of life. Melatonin has been shown to improve sleep in PD patients. This pilot study aimed at evaluating the effects of a 3-month treatment with 2 mg melatonin prolonged-release (PR) on sleep and motor disability in PD patients. Materials and methods Twelve PD patients under stable antiparkinsonian treatment were enrolled in the study. Before treatment (T0), motor dysfunction was assessed with Unified Parkinson’s Disease Rating Scale (UPDRS-III) and sleep architecture with polysomnography. Subjective sleep quality was also assessed through Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence with Epworth Sleepiness Scale (ESS). Patients then started melatonin PR and all measures were repeated at the end of treatment after 3 months (T1). Results Sleep latency significantly decreased from T0 to T1, but no other significant differences were found in PSG parameters. Melatonin PR treatment significantly reduced the ESS scores from T0 to T1, while the PSQI scores presented a trend of improvement from T0 to T1. Motor dysfunction was not improved by melatonin PR, although there was a trend in decreasing UPDRS-III. Both clinical global improvement and patient clinical global impression documented an improvement in insomnia symptoms at T1. Conclusions These findings suggest that melatonin may improve sleep symptoms in PD patients, although further evidence is needed in larger controlled studies to confirm these results and explore the possible direct and indirect influence of sleep improvement on motor dysfunction.

Background: Several biomarkers have been evaluated in Parkinson’s disease (PD); cerebrospinal fluid (CSF) levels of lactate may reflect cerebral metabolism function and CSF amyloid-β42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau) concentrations may detect an underlying neurodegenerative process. Objective: CSF levels of lactate, Aβ42, t-tau, and p-tau were measured in patients with mild to moderate PD. CSF levels of dopamine (DA) and its metabolite 3,4-Dihydroxyphenylacetic acid (DOPAC) were also assessed, exploring their relations with the other CSF biomarkers. Methods: 101 drug-naive PD patients and 60 controls were included. Participants underwent clinical assessments and CSF biomarker analysis. Patients were divided into subgroups according to their Hoehn & Yahr stage (PD-1, PD-2, PD-3). Results: PD patients showed higher lactate levels (M = 1.91; p = 0.03) and lower Aβ42 (M = 595; p

This study aimed to assess the sleep-wake pattern in patients with epilepsy compared to controls.Patients with epilepsy and controls underwent a 14-day actigraphic recording to evaluate the rest-activity cycle. A sleep medicine interview was performed to exclude conditions interfering with the sleep-wake cycle in both patients and controls. Patients presenting seizures during the actigraphic recording were excluded. Daytime activity, nocturnal sleep, and non-parametric circadian rhythm activity (NPCRA) were analysed.Twenty-two patients (mean age 49.5 ± 19.84 years; 50% female) and 17 controls were included. Patients showed lower sleep efficiency and longer sleep latency than controls. NPCRA analysis showed lower inter-daily stability and higher intra-daily variability in patients, who also presented lower daytime activity and a longer central phase measure (CPM) than controls.Patients showed a significant alteration of the sleep-wake pattern, featured by lower synchronization and higher fragmentation of the rest-activity rhythm. Moreover, patients showed a delayed CPM compared with controls, corresponding to an evening chronotype tendency. Nocturnal sleep alteration and lower daytime activity were also evident. Therefore, patients with epilepsy present an alteration of the sleep-wake pattern and clinicians should increase their awareness about circadian rhythmicity dysregulation in epilepsy.

Neuropeptides orexin A and B (OX-A/B, also called hypocretin 1 and 2) are released selectively by a population of neurons which projects widely into the entire central nervous system but are localized in a restricted area of the tuberal region of the hypothalamus, caudal to the paraventricular nucleus. The OX system prominently targets brain structures involved in the regulation of wake-sleep state switching, and also orchestrates multiple physiological functions. The degeneration and dysregulation of the OX system promotes narcoleptic phenotypes both in humans and animals. Hence, this review begins with the already proven involvement of OX in narcolepsy, but it mainly discusses the new pre-clinical and clinical insights of the role of OX in three major neurological disorders characterized by sleep impairment which have been recently associated with OX dysfunction, such as Alzheimer's disease, stroke and Prader Willi syndrome, and have been emerged over the past 10 years to be strongly associated with the OX dysfunction and should be more considered in the future. In the light of the impairment of the OX system in these neurological disorders, it is conceivable to speculate that the integrity of the OX system is necessary for a healthy functioning body.

Objective Epilepsy treatment during pregnancy is still challenging. The study is aimed at comparing the efficacy and safety of carbamazepine (CBZ), lamotrigine (LTG) and levetiracetam (LEV) monotherapies during pregnancy in women with focal (FE) or generalized (GE) epilepsy. Methods A multicentre retrospective study was conducted to evaluate seizures frequency and seizure freedom (SF) rate during 3 months before pregnancy, each trimester of gestation and post-partum period in women on monotherapy with CBZ, LTG and LEV. Results Fifty-seven pregnancies (45 FE, 12 GE) on monotherapy (29 CBZ, 11 LTG, 17 LEV) were included. A significant reduction of seizure frequency was found in the first trimester of pregnancy as compared with that one before pregnancy (p = 0.004), more evident in GE (p = 0.003) and in LEV group (p = 0.004). The SF rate significantly increased in the first trimester in comparison to that one before pregnancy and persisted in the post-partum period in the whole sample (p p = 0.004). Besides, 88.57% of SF women before pregnancy remained unchanged during gestation and the post-partum period. One major heart malformation in CBZ and no major malformations in LTG and LEV groups were found. Conclusions A better clinical outcome during pregnancy emerged since the first trimester in comparison to the before-pregnancy period, mostly evident in women with GE and LEV therapy, reinforcing the hypothesis of a protective role of pregnancy versus seizures. SF before pregnancy represents a significant predictive factor of good clinical outcome during gestation and the post-partum period. Compared to CBZ, LTG and LEV showed a better safety profile.