Epidemiology of seropositive myasthenia gravis in Sardinia: A population-based study in the district of Sassari.

INTRODUCTION/AIMS: The global incidence and prevalence of myasthenia gravis (MG) range between 6-31/million and 10-37/100,000, respectively. Sardinia is a high-risk region for different immune-mediated disorders, but the epidemiology of MG remains unclear. We determined the epidemiology of MG with acetylcholine receptor (AChR)-immunoglobulin G (IgG) and muscle-specific tyrosine kinase (MuSK)-IgG in the district of Sassari (North-Western Sardinia; population, 325,288). METHODS: From the laboratory of the University Hospital of Sassari (reference for AChR/MuSK-IgG testing in Sardinia since 1998) and the main neurology units in Sardinia, we retrospectively identified MG patients with (1) AChR-IgG and/or MuSK-IgG positivity by radioimmunoprecipitation assay; and (2) residency in the district of Sassari. Incidence (January 2010-December 2019) and prevalence (December 31, 2019) were calculated. RESULTS: A total of 202 patients were included (incident, 107; prevalent, 180). Antibody specificities were AChR (n = 187 [93%]) and MuSK (n = 15 [7%]). The crude MG incidence (95% confidence interval) was 32.6 (26.8-39.2)/million, while prevalence was 55.3 (47.7-63.9)/100,000. After age-standardization to the world population, incidence decreased to 18.4 (14.3-22.5)/million, while prevalence decreased to 31.6 (26.1-37.0)/100,000. Among incident cases, age strata (years) at MG onset were: <18 (2%), 18-49 (14%), 50-64 (21%), and ≥65 (63%). DISCUSSION: Sardinia is a high-risk region for MG, with a prevalence that exceeds the European threshold for rare disease. Identification of the environmental and genetic determinants of this risk may improve our understanding of disease pathophysiology.

Prevalence of sleep disruption and determinants of sleepiness in a cohort of Italian hospital physicians: The PRESOMO study.

Nightshift work can cause daytime somnolence and decreased alertness, and can increase risk of medical errors, occupational injuries and car accidents. We used a structured questionnaire, including the Epworth Sleepiness Scale (ESS), to assess the prevalence and the determinants of sleep disruption in 268 Italian University hospital physicians from Cagliari (N = 57), Milan (N = 180) and Pisa (N = 31), who participated in the multicentre study on the prevalence of sleep disturbance among hospital physicians (PRESOMO); 198 of them (74%) were engaged in nightshift work. We explored the association between history of nightshift work and poor sleep quality and daytime somnolence with multivariate logistic regression, adjusting by personal and lifestyle covariates. Age, female gender, taking medication interfering with sleep and an elevated ESS score were significant predictors of poor sleep quality and daytime somnolence. Nightshift work was associated with a higher prevalence of unrestful sleep (84% versus 70%; odds ratio [OR] = 2.4, 95% confidence interval [CI] 1.18-5.05) and daytime dozing (57% versus 35%; OR = 1.9, 95% CI 1.03-3.64), with an upward trend by years of engagement in nightshift work for both conditions (p = .043 and 0.017, respectively), and by number of nightshifts/year for unrestful sleep (p = .024). Such an association was not detected with the ESS scale. Our results suggest that nightshift work significantly affects sleep quality and daytime somnolence in hospital physicians, who might underestimate their daytime dozing problem, when asked to subjectively scale it.

Predictive risk factors of phenoconversion in idiopathic REM sleep behavior disorder: the Italian study "FARPRESTO".

Most patients with idiopathic REM sleep behavior disorder (iRBD) will develop an overt α-synucleinopathy over time, with a rate of phenoconversion of 73.5% after 12 years from diagnosis. Several markers of phenoconversion were identified; however, most studies investigated biomarkers separately, with retrospective study designs, in small cohorts or without standardized data collection methods. The risk FActoRs PREdictive of phenoconversion in idiopathic REM sleep behavior disorder: the Italian STudy (FARPRESTO) is a multicentric longitudinal retrospective and prospective study with a cohort of incident (prospective recruitment) and prevalent (retrospective recruitment) iRBD patients, whose primary aim is to stratify the risk of phenoconversion, through the systematic collection by means of electronic case report forms of different biomarkers. Secondary aims are to (1) describe the sociodemographic and clinical characteristics of patients with iRBD; (2) collect longitudinal data about the development of α-synucleinopathies; (3) monitor the impact of iRBD on quality of life and sleep quality; (4) assess the correlation between phenoconversion, cognitive performance, and loss of normal muscle atony during REM sleep; (5) identify RBD phenotypes through evaluating clinical, biological, neurophysiological, neuropsychological, and imaging biomarkers; and (6) validate vPSG criteria for RBD diagnosis. The FARPRESTO study will collect a large and harmonized dataset, assessing the role of different biomarkers providing a unique opportunity for a holistic, multidimensional, and personalized approach to iRBD, with several possible application and impact at different levels, from basic to clinical research, and from prevention to management. The FARPRESTO has been registered at clinicaltrials.gov (NCT05262543).

Prolonged epileptic discharges predict seizure recurrence in JME: Insights from prolonged ambulatory EEG.

OBJECTIVE: Markers of seizure recurrence are needed to personalize antiseizure medication (ASM) therapy. In the clinical practice, EEG features are considered to be related to the risk of seizure recurrence for genetic generalized epilepsies (GGE). However, to our knowledge, there are no studies analyzing systematically specific EEG features as indices of ASM efficacy in GGE. In this study, we aimed at identifying EEG indicators of ASM responsiveness in Juvenile Myoclonic Epilepsy (JME), which, among GGE, is characterized by specific electroclinical features. METHODS: We compared the features of prolonged ambulatory EEG (paEEG, 22 h of recording) of JME patients experiencing seizure recurrence within a year ("cases") after EEG recording, with those of patients with sustained seizure freedom for at least 1 year after EEG ("controls"). We included only EEG recordings of patients who had maintained the same ASM regimen (dosage and type) throughout the whole time period from the EEG recording up to the outcome events (which was seizure recurrence for the "cases", or 1-year seizure freedom for "controls"). As predictors, we evaluated the total number, frequency, mean and maximum duration of epileptiform discharges (EDs) and spike density (i.e. total EDs duration/artifact-free EEG duration) recorded during the paEEG. The same indexes were assessed also in standard EEG (stEEG), including activation methods. RESULTS: Both the maximum length and the mean duration of EDs recorded during paEEG significantly differed between cases and controls; when combined in a binary logistic regression model, the maximum length of EDs emerged as the only valid predictor. A cut-off of EDs duration of 2.68 seconds discriminated between cases and controls with a 100% specificity and a 93% sensitivity. The same indexes collected during stEEG lacked both specificity and sensitivity. SIGNIFICANCE: The occurrence of prolonged EDs in EEG recording might represent an indicator of antiepileptic drug failure in JME patients.

Heart rate detection by Fitbit ChargeHR™ : A validation study versus portable polysomnography.

Consumer "Smartbands" can collect physiological parameters, such as heart rate (HR), continuously across the sleep-wake cycle. Nevertheless, the quality of HR data detected by such devices and their place in the research and clinical field is debatable, as they are rarely rigorously validated. The objective of the present study was to investigate the reliability of pulse photoplethysmographic detection by the Fitbit ChargeHR™ (FBCHR, Fitbit Inc.) in a natural setting of continuous recording across vigilance states. To fulfil this aim, concurrent portable polysomnographic (pPSG) and the Fitbit's photoplethysmographic data were collected from a group of 25 healthy young adults, for ≥12 hr. The pPSG-derived HR was automatically computed and visually verified for each 1-min epoch, while the FBCHR HR measurements were downloaded from the application programming interface provided by the manufacturer. The FBCHR was generally accurate in estimating the HR, with a mean (SD) difference of -0.66 (0.04) beats/min (bpm) versus the pPSG-derived HR reference, and an overall Pearson's correlation coefficient (r) of 0.93 (average per participant r = 0.85 ± 0.11), regardless of vigilance state. The correlation coefficients were larger during all sleep phases (rapid eye movement, r = 0.9662; N1, r = 0.9918; N2, r = 0.9793; N3, r = 0.9849) than in wakefulness (r = 0.8432). Moreover, the correlation coefficient was lower for HRs of >100 bpm (r = 0.374) than for HRs of <100 bpm (r = 0.84). Consistently, Bland-Altman analysis supports the overall higher accuracy in the detection of HR during sleep. The relatively high accuracy of FBCHR pulse rate detection during sleep makes this device suitable for sleep-related research applications in healthy participants, under free-living conditions.

Prolonged and short epileptiform discharges have an opposite relationship with the sleep-wake cycle in patients with JME: Implications for EEG recording protocols.

In a recent study, we found that during 20.55 ±â€¯1.60 h of artifact-free ambulatory EEG recordings, epileptiform discharges (EDs) longer than 2.68 s occurred exclusively in patients with Juvenile Myoclonic Epilepsy (JME) who experienced seizure recurrence within a year after the EEG. Here we expanded this analysis, exploring whether long EDs (>2.68 s), and short ones, were uniformly distributed during the day. Lastly, we evaluated the temporal distribution of seizure relapses. By Friedman test, we demonstrated that hourly frequencies of both short and long EDs were dependent on the hours of day and sleep-wake cycle factors, with an opposite trend. Short EDs were found mostly during the night (with two peaks at 1 AM and 6 AM), and sleep, dropping at the wake onset (p < 0.001). Conversely, long EDs surged at the wake onset (0.001), remaining frequent during the whole wake period, when compared to sleep (p = 0.002). Of note, this latter pattern mirrored that of seizures, which occurred exclusively during the wake period, and in 9 out of 13 cases at the wake onset. We therefore suggested that short and long EDs could reflect distinct pathophysiological phenomena. Extended wake EEG recordings, possibly including the awakening, could be extremely useful in clinical practice, as well as in further studies, with the ambitious goal of predicting seizure recurrences.

Obstructive sleep apnea syndrome and Alzheimer's disease pathology: may continuous positive airway pressure treatment delay cognitive deterioration?

PURPOSE: The main aim of the present study was to identify the long-term effects of continuous positive airway pressure (CPAP) treatment in patients co-affected by obstructive sleep apnea syndrome (OSAS) and mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (ADD). METHODS: This retrospective multicentre study included patients affected by MCI or ADD, diagnosed according to the core clinical and biomarkers criteria, and presenting comorbid OSAS. Only patients performing at least a 1-year visit during their follow-up to monitor cognitive deterioration and adherence with CPAP treatment were included. Both Mini-Mental State Examination (MMSE) and clinical dementia rating scale (CDR) were conducted during the baseline and the follow-up visits. RESULTS: Twenty-four patients were included in the study and were distributed according to the diagnosis in MCI (n = 8) or ADD (n = 16). There were no significant differences in the variables analysed at baseline between the CPAP non-adherent and CPAP adherent patients. In the whole group, a significant decrease was found in MMSE scores, and a significant increase was found in CDR scores between baseline and follow-up. No longitudinal changes in ESS scores were statistically significant from baseline to follow-up. A significant difference was found for the mean score change of the CDR since CPAP non-adherent patients showed a higher mean change of CDR compared to CPAP adherent patients. No significant differences were found for the mean change of MMSE. CONCLUSION: These findings highlight the clinical potential of treating OSAS with CPAP to delay cognitive deterioration in patients with MCI or ADD.

Excessive daytime sleepiness and fatigue in neurological disorders.

Excessive daytime sleepiness (EDS) and fatigue are some of the most frequent symptoms in neurological diseases and could impact on quality of life by increasing the risk of accidents and generally affecting daily life activities. In this review, we will examine the variety of causes responsible for EDS in neurological diseases, including nocturnal sleep alterations, CNS pathological abnormalities with alterations in arousal and/or REM regulation systems, circadian rhythms disorders, drugs, and comorbid psychiatric or primary sleep disorders. Among neurological diseases, epilepsy, dementia, Parkinson disease, multiple sclerosis, and myotonic dystrophies represented a model for these interactions between EDS and neurological diseases. A complete diagnostic workup in neurological patients with EDS should be undertaken since EDS can worsen many different aspects such as psychiatric symptoms, cognitive deficit, and in some cases, the severity of the neurological disease per se. Moreover, quality of life and risk of accidents are dependent on EDS. An individualized approach to this symptom in neurological patients should be considered with a focus on modifiable causes such as SDB, psychiatric comorbidities, and drugs. When considering EDS and fatigue in neurological diseases, close attention to lifestyle and sleep hygiene is advisable. A critical review of ongoing pharmacological therapy should not be overlooked. Possible diagnosis and treatment of SDB should be always considered.

A longitudinal study of polysomnographic variables in patients with mild cognitive impairment converting to Alzheimer's disease.

The main condition at increased risk of dementia is considered to be mild cognitive impairment. Mild cognitive impairment has been defined as a transitional state between normal aging and dementia, of which it may represent a prodrome. The aim of our study was to evaluate whether sleep variables (both conventional and microstructural ones) in subjects with mild cognitive impairment correlate with conversion to dementia. Nineteen subjects with amnestic mild cognitive impairment (mean age 68.5 ±â€…7.0 years) and 11 cognitively intact healthy elderly individuals (mean age 69.2 ±â€…12.6 years) underwent ambulatory polysomnography for the evaluation of nocturnal sleep architecture and cyclic alternating pattern parameters. Amnestic mild cognitive impairment subjects were clinically and cognitively re-evaluated after 2 years, during routine follow-up, and further classified as amnestic mild cognitive impairment converters (that is, patients developing Alzheimer's disease, N = 11) and amnestic mild cognitive impairment non-converters. Compared with healthy elderly individuals, amnestic mild cognitive impairment showed disrupted sleep with decreased rapid eye movement sleep, cyclic alternating pattern rate and cyclic alternating pattern slow-wave-related phases (A1 index). Standard sleep architecture analysis did not show significant differences between the two subgroups of amnestic mild cognitive impairment, whereas cyclic alternating pattern analysis showed that cyclic alternating pattern rate, A1 index and A3 index are significantly reduced in converters compared with non-converters. Our data confirm that in amnestic mild cognitive impairment subjects there is a sleep impairment, particularly when considering more refined sleep parameters and that sleep variables at baseline are different among converters versus non-converters at the 2-year follow-up. Specific sleep alterations might represent potential further biomarkers for the diagnosis and prognosis of early-phase cognitive impairment.

Sleep Complaints, Sleep and Breathing Disorders in Myotonic Dystrophy Type 2.

PURPOSE OF REVIEW: To update the current knowledge concerning sleep complaints and breathing disorders in myotonic dystrophy type 2 (DM2) and to better understand if sleep and breathing symptoms may add a further clinical definition of DM2. RECENT FINDINGS: Although DM2 has been poorly evaluated, the most relevant sleep disorders are sleep-disordered breathing (SDB) (37.5-66.7%) and restless legs syndrome (RLS) (50-60%). Excessive daytime somnolence (EDS) is not consistent with SDB, and a large percentage of patients with sleep complaints (58-69%) report pain. In addition, respiratory dysfunctions are reported in 6 to 15% of DM2 patients, albeit few data are available regarding pulmonary restriction, hypoventilation, and non-invasive ventilation (NIV). SDB, RLS, and pain may contribute to sleep fragmentation and EDS in DM2. In addition, few studies report hypoventilation and pulmonary restriction, although there are no studies at all on NIV, except for limited clinical experiences. These findings suggest performing a careful pulmonary examination and NIV when required. Furthermore, sleep studies and respiratory evaluation should be recommended if OSA or respiratory muscle dysfunctions are suspected. A large polysomnographic study should be performed to clarify the link between sleep disorders, pain, and sleep disruption in DM2.

IgG4 autoantibodies against muscle-specific kinase undergo Fab-arm exchange in myasthenia gravis patients.

Autoimmunity mediated by IgG4 subclass autoantibodies is an expanding field of research. Due to their structural characteristics a key feature of IgG4 antibodies is the ability to exchange Fab-arms with other, unrelated, IgG4 molecules, making the IgG4 molecule potentially monovalent for the specific antigen. However, whether those disease-associated antigen-specific IgG4 are mono- or divalent for their antigens is unknown. Myasthenia gravis (MG) with antibodies to muscle specific kinase (MuSK-MG) is a well-recognized disease in which the predominant pathogenic IgG4 antibody binds to extracellular epitopes on MuSK at the neuromuscular junction; this inhibits a pathway that clusters the acetylcholine (neurotransmitter) receptors and leads to failure of neuromuscular transmission. In vitro Fab-arm exchange-inducing conditions were applied to MuSK antibodies in sera, purified IgG4 and IgG1-3 sub-fractions. Solid-phase cross-linking assays were established to determine the extent of pre-existing and inducible Fab-arm exchange. Functional effects of the resulting populations of IgG4 antibodies were determined by measuring inhibition of agrin-induced AChR clustering in C2C12 cells. To confirm the results, κ/κ, λ/λ and hybrid κ/λ IgG4s were isolated and tested for MuSK antibodies. At least fifty percent of patients had IgG4, but not IgG1-3, MuSK antibodies that could undergo Fab-arm exchange in vitro under reducing conditions. Also MuSK antibodies were found in vivo that were divalent (monospecific for MuSK). Fab-arm exchange with normal human IgG4 did not prevent the inhibitory effect of serum derived MuSK antibodies on AChR clustering in C2C12 mouse myotubes. The results suggest that a considerable proportion of MuSK IgG4 could already be Fab-arm exchanged in vivo. This was confirmed by isolating endogenous IgG4 MuSK antibodies containing both κ and λ light chains, i.e. hybrid IgG4 molecules. These new findings demonstrate that Fab-arm exchanged antibodies are pathogenic.

Cyclic alternating pattern and interictal epileptiform discharges during morning sleep after sleep deprivation in temporal lobe epilepsy.

PURPOSE: Sleep deprivation (SD) increases the occurrence of interictal epileptiform discharges (IED) compared to basal EEG in temporal lobe epilepsy (TLE). In adults, EEG after SD is usually performed in the morning after SD. We aimed to evaluate whether morning sleep after SD bears additional IED-inducing effects compared with nocturnal physiological sleep, and whether changes in sleep stability (described by the cyclic alternating pattern-CAP) play a significant role. METHODS: Adult patients with TLE underwent in-lab night polysomnography (n-PSG) and, within 7days from n-PSG, they underwent also a morning EEG after night SD (SD-EEG). We included only TLE patients in which both recordings showed IED. SD-EEG consisted of waking up patients at 2:00 AM and performing video EEG at 8:00 AM. For both recordings, we obtained the following markers for the first sleep cycle: IED/h (Spike Index, SI), sleep macrostructure, microstructure (NREM CAP rate; A1, A2 and A3 Indices), and SI association with CAP variables. RESULTS: The macrostructure of the first sleep cycle was similar in n-PSG and morning SD-EEG, whereas CAP rate and SI were significantly higher in SD-EEG. SI increase was selectively associated with CAP phases. CONCLUSIONS: SD increases the instability of morning recovery sleep compared with n-PSG, and particularly enhances CAP A1 phases, which are associated with the majority of IED. Thus, higher instability of morning recovery sleep may account at least in part for the increased IED yield in SD-EEG in TLE patients.

Relationship quality of persons with obstructive sleep apnoea syndrome.

In the field of sleep disorders, the quality of couple relationship is arousing increasing attention, given its implications for quality of life and treatment adherence. The aim of the present study was to evaluate relationship quality in a sample of treated or untreated patients with Obstructive Sleep Apnoea Syndrome. Eighty-seven patients were recruited in a hospital-based Centre for Sleep Medicine. Subjects were administered the Dyadic Adjustment Scale (DAS) to evaluate relationship quality, and the Epworth Sleepiness Scale (ESS). Apnoea-hypopnoea indexes (AHI) were collected through nocturnal polysomnography or home testing with a portable monitoring device. Although the DAS average scores were similar to local normative values, relationship quality was significantly lower in the untreated patients when compared with the ones treated. The ESS scores showed a negative correlation with many DAS scores, whereas no significant correlation emerged for AHI. Such data suggest a significant impact of perceived sleep apnoea symptoms on marital satisfaction, even though in the absence of striking differences between the whole sample and the general population.

Psychological well-being of patients with insomnia and its relationship with anxiety and depression.

The aims of the present study are to evaluate the impact of insomnia on psychological well-being and to examine the associations of insomnia and psychological well-being with anxiety and depression. Forty-one patients attending our hospital-based Centre for sleep medicine were administered scales for the evaluation of insomnia (ISI), anxiety (STAI-Y), depression (BDI-II) and psychological well-being (PWB). The scores were compared to those of a control group of 68 subjects attending the hospital for routine examinations or as accompanying persons. Significant differences between patients and controls were detected for anxiety and depression, as well as for psychological well-being. Even if subclinical on average, anxiety and depression symptoms were significantly related to poor psychological well-being, whereas insomnia per se was not. These findings suggest that patients with insomnia report a relevant impact on their psychological well-being, and that such an impact seems to be strongly associated with concomitant subthreshold symptoms of anxiety and depression. The implications for diagnosis and treatment are discussed.

Gene-Specific Methylation Analysis in Thymomas of Patients with Myasthenia Gravis.

Thymomas are uncommon neoplasms that arise from epithelial cells of the thymus and are often associated with myasthenia gravis (MG), an autoimmune disease characterized by autoantibodies directed to different targets at the neuromuscular junction. Little is known, however, concerning epigenetic changes occurring in thymomas from MG individuals. To further address this issue, we analyzed DNA methylation levels of genes involved in one-carbon metabolism (MTHFR) and DNA methylation (DNMT1, DNMT3A, and DNMT3B) in blood, tumor tissue, and healthy thymic epithelial cells from MG patients that underwent a surgical resection of a thymic neoplasm. For the analyses we applied the methylation-sensitive high-resolution melting technique. Both MTHFR and DNMT3A promoters showed significantly higher methylation in tumor tissue with respect to blood, and MTHFR also showed significantly higher methylation levels in tumor tissue respect to healthy adjacent thymic epithelial cells. Both DNMT1 and DNMT3B promoter regions were mostly hypomethylated in all the investigated tissues. The present study suggests that MTHFR methylation is increased in thymomas obtained from MG patients; furthermore, some degrees of methylation of the DNMT3A gene were observed in thymic tissue with respect to blood.

Daytime rumination as a feature of Insomnia Disorder: sleep related cognition is not merely a problem of the night.

Night-time sleep related cognitions have been shown to play a perpetuating role in insomnia. According to the cognitive model of insomnia day time cognitions (i.e. worry, rumination, etc.) may also contribute to it. The aim of this study was to investigate the possible role of daytime sleep-related rumination in Insomnia Disorder (n= 55, mean age 49.7±16.7 years), Obstructive Sleep Apnea Syndrome (OSAS) (n=33, mean age 58.1±10.2 years) and healthy subjects (n=33, mean age 49.8±13.9), using a set of sleep related variables which included the Daytime Insomnia Symptom Response Scale (DISRS), the Dysfunctional Beliefs about Sleep Scale (DBAS), the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). Daytime sleep related rumination was higher in insomnia when compared to both OSAS (p<.001) and good sleepers (p<.001). In insomnia, elevated sleep related daytime rumination was best determined by unhelpful sleep related beliefs (coeff=0.3 p=.004), while in OSAS by insomnia symptoms (coeff=0.9, p=.02). These findings suggest that the association between insomnia-specific daytimerumination and unhelpful beliefs may be considered a cognitive feature of insomnia. In insomnia, sleep related cognition may dominate the 24-hour period. This finding might be of use for further investigations studying therapeutic strategies acting on cognitive processes to prevent and treat insomnia disorder and its comorbid conditions.

NREM sleep transient events in fronto-temporal dementia: beyond sleep stage architecture.

Frontotemporal dementia (FTD) is increasingly becoming recognized as a major cause of early onset (<65 years) neurodegenerative dementia. Although sleep disorders significantly impair patients' and caregivers' quality of life in neurodegenerative diseases, polysomnographic data in FTD patients are scarce in literature. Aim of our study was to investigate sleep microstructure in FTD, by means of Cyclic Alternating Pattern (CAP), in a group of ten behavioral variant FTD patients (6 M, 4 F; mean age 61.2±7.3 years; disease duration: 1.4±0.7 years) and to compare them with cognitively intact healthy elderly. Sleep in FTD patients was altered at different levels, involving not only the conventional sleep stage architecture parameters (total sleep time, single stage percentage, NREM/REM cycle organization), but also microstructure. FTD subjects showed CAP disruption with decreased slow wave activity related phases (A1 index, n/h:14.5±6.8 vs 38.8±6.6; p<.001) and increased arousal-related fast CAP components (A2 index 22.9±8.2 vs 11.6±3.7; p=.006; A3 index 41.9±20.7 vs 13.0±6.5; p=.002). Several correlations between sleep variables and neuropsychological tests were found. Sleep impairment in FTD may be specifically related to the specific frontal lobe involvement in the neurodegenerative process. The pattern of alterations seems somewhat peculiar, probably due to the anatomical distribution of the neurodegenerative process with a major impact on frontal lobe generated sleep transients, and a substantial sparing of phenomena related to the posterior cortex.

A retrospective multicenter study on clinical and serological parameters in patients with MuSK myasthenia gravis with and without general immunosuppression.

Introduction: Muscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of the IgG4 subclass. The first-line treatment for MuSK-MG is general immunosuppression with corticosteroids, but the effect of treatment on IgG4 and MuSK IgG4 levels has not been studied. Methods: We analyzed the clinical data and sera from 52 MuSK-MG patients (45 female, 7 male, median age 49 (range 17-79) years) from Italy, the Netherlands, Greece and Belgium, and 43 AChR-MG patients (22 female, 21 male, median age 63 (range 2-82) years) from Italy, receiving different types of immunosuppression, and sera from 46 age- and sex-matched non-disease controls (with no diagnosed diseases, 38 female, 8 male, median age 51.5 (range 20-68) years) from the Netherlands. We analyzed the disease severity (assessed by MGFA or QMG score), and measured concentrations of MuSK IgG4, MuSK IgG, total IgG4 and total IgG in the sera by ELISA, RIA and nephelometry. Results: We observed that MuSK-MG patients showed a robust clinical improvement and reduction of MuSK IgG after therapy, and that MuSK IgG4 concentrations, but not total IgG4 concentrations, correlated with clinical severity. MuSK IgG and MuSK IgG4 concentrations were reduced after immunosuppression in 4/5 individuals with before-after data, but data from non-linked patient samples showed no difference. Total serum IgG4 levels were within the normal range, with IgG4 levels above threshold (1.35g/L) in 1/52 MuSK-MG, 2/43 AChR-MG patients and 1/45 non-disease controls. MuSK-MG patients improved within the first four years after disease onset, but no further clinical improvement or reduction of MuSK IgG4 were observed four years later, and only 14/52 (26.92%) patients in total, of which 13 (93.3%) received general immunosuppression, reached clinical remission. Discussion: We conclude that MuSK-MG patients improve clinically with general immunosuppression but may require further treatment to reach remission. Longitudinal testing of individual patients may be clinically more useful than single measurements of MuSK IgG4. No significant differences in the serum IgG4 concentrations and IgG4/IgG ratio between AChR- and MuSK-MG patients were found during follow-up. Further studies with larger patient and control cohorts are necessary to validate the findings.

National Multicenter Study on the Comparison of Robotic and Open Thymectomy for Thymic Neoplasms in Myasthenic Patients: Surgical, Neurological and Oncological Outcomes.

Thymectomy is the gold standard in the treatment of thymic neoplasm and plays a key role in the therapeutic path of myasthenia gravis. For years, sternotomy has been the traditional approach for removing anterior mediastinal lesions, although the robotic thymectomy is now widely performed. The literature is still lacking in papers comparing the two approaches and evaluating long-term oncological and neurological outcomes. This study aims to analyze the postoperative results of open and robotic thymectomy for thymic neoplasms in myasthenic patients. Surgical, oncological and neurological data of myasthenic patients affected by thymic neoplasms and surgically treated with extended thymectomy, both with the open and the robotic approach, in six Italian Thoracic Centers between 2011 and 2021 were evaluated. A total of 213 patients were enrolled in the study: 110 (51.6%) were treated with the open approach, and 103 (48.4%) were treated with robotic surgery. The open surgery, compared with the robotic, presented a shorter operating time (p < 0.001), a higher number of postoperative complications (p = 0.038) and longer postoperative hospitalization (p = 0.006). No other differences were observed in terms of surgical, oncological or neurological outcomes. The robotic approach can be considered safe and feasible, comparable to the open technique, in terms of surgical, oncological and neurological outcomes.