Next-generation sequencing in Charcot-Marie-Tooth: a proposal for improvement of ACMG guidelines for variant evaluation.

BACKGROUND: The application of massive parallel sequencing technologies in the molecular analysis of Charcot-Marie-Tooth (CMT) has enabled the rapid and cost-effective identification of numerous potentially significant variants for diagnostic purposes. The objective is to reduce the number of variants, focusing only on those with pathogenic significance. The 2015 American College of Medical Genetics and Genomics (ACMG) guidelines aid in achieving this goal, but it is now evident that a pathology or gene-specific review of these rules is essential to avoid misinterpretations that may result from blindly applying the criteria. This study demonstrates how revised ACMG criteria, combined with CMT-specific literature data and expertise, can alter the final classification of a variant. METHODS: We reviewed ACMG criteria based on current knowledge of CMT and provided suggestions for adapting them to the specificities of CMT. RESULTS: Of the 226 index patients analysed, a diagnostic yield of 20% was obtained. It is worth noting that the 9% of cases had their final diagnosis changed with the application of the revised criteria, often resulting in the loss of the pathogenic classification of a variant. CONCLUSIONS: The widespread availability of high-throughput sequencing technologies has enabled genetic testing even for laboratories without specific disease expertise. Disease-specific ACMG criteria can be a valuable tool to prevent the proliferation of variants of uncertain significance and the misinterpretation of variants.

Exploring the neural basis of non-invasive prehabilitation in brain tumour patients: An fMRI-based case report of language network plasticity.

Primary brain neoplasms are associated with elevated mortality and morbidity rates. Brain tumour surgery aims to achieve maximal tumour resection while minimizing damage to healthy brain tissue. Research on Neuromodulation Induced Cortical Prehabilitation (NICP) has highlighted the potential, before neurosurgery, of establishing new brain connections and transfer functional activity from one area of the brain to another. Nonetheless, the neural mechanisms underlying these processes, particularly in the context of space-occupying lesions, remain unclear. A patient with a left frontotemporoinsular tumour underwent a prehabilitation protocol providing 20 sessions of inhibitory non-invasive neuromodulation (rTMS and multichannel tDCS) over a language network coupled with intensive task training. Prehabilitation resulted in an increment of the distance between the tumour and the language network. Furthermore, enhanced functional connectivity within the language circuit was observed. The present innovative case-study exposed that inhibition of the functional network area surrounding the space-occupying lesion promotes a plastic change in the network's spatial organization, presumably through the establishment of novel functional pathways away from the lesion's site. While these outcomes are promising, prudence dictates the need for larger studies to confirm and generalize these findings.

Online Questionnaire with Fibromyalgia Patients Shows Negative Correlations between Disease Severity and Adherence to Mediterranean Diet.

Fibromyalgia (FM) is a multidimensional disorder in which intense chronic pain is accompanied by a variety of psychophysical symptoms that impose a burden on the patients' quality of life. Despite the efforts and the recent advancement in research, FM pathogenesis and effective treatment remain unknown. Recently, the possible role of dietary patterns and/or components has been gaining attention. The current study aimed to investigate a potential correlation between adherence to the Mediterranean diet (MedDiet) and FM severity in a sample of Italian FM patients. An online survey was designed, composed of customized questions and validated questionnaires with the aim of investigating the intensity and type of pain, the presence of other psychophysical symptoms, the overall impact of FM, general food and lifestyle habits, and adherence to the MedDiet. The collected responses were analyzed for descriptive statistics, linear regression, and propensity score analyses. The results show that, despite considerable use of pharmaceuticals and supplements, FM participants suffered from a high-severity grade disease. However, those with good adherence to the MedDiet experienced a lower pain intensity and overall FM impact. A propensity score analysis indicates a positive influence of the MedDiet against FM severity, thus unveiling the need for well-designed intervention studies to evaluate the therapeutic potential of different dietary patterns.

Frequency of brain ventricular enlargement among patients with diabetes mellitus.

AIMS: To determine the prevalence of dilated ventricles and concomitant high blood glucose measures. METHODS: We retrieved blood glucose measures from the emergency department database and selected a subgroup of individuals having both the radiological marker Evans' index (EI) values and blood glucose measures. RESULTS: Out of 1221 consecutive patients submitted to axial Computed Tomography scans, a blood glucose measure was detected in 841 individuals. 176 scans (21 %) showed an EI > 0.30. According to the blood glucose categorization, diabetic patients were 104 (12 %), 25 of them (24 %) were dilated (mean EI 0.33). The age difference between dilated and not-dilated ventricles is about ten years in not-diabetic participants, whereas it is five years in diabetic participants. The age difference between dilated and not-dilated ventricles is about 10 years in diabetic men, whereas it zero in diabetic women. CONCLUSIONS: Pathological ventricular enlargement is more frequent in men and in the elderly. In diabetic patients (especially women), the cerebral ventricles enlarge faster than in non-diabetic individuals. Age, sex, and diabetes may interact in determining how cerebral ventricle size changes over time, especially in diabetic women, making routine brain imaging advisable in these patients after the age of 70 years.

Patient With Rigidity and Fasciculations: Steroid-Responsive Presentation of Anti-IgLON5 Disease

An 82-year-old man presented with 2-year lasting widespread muscular fasciculations, cramps, and limb stiffness, with spontaneous movements in the right lower limb, unsteady gait (Video 1), and falls. Neurophysiologic studies disclosed signs of neuromuscular hyperexcitability. CSF analysis showed high tau protein concentration (543 pg/mL; reference values, <404) and unique-to-CSF oligoclonal bands. Serum and CSF anti-IgLON5 antibodies were positive (Figure 1). He carried the anti-IgLON5 disease-associated HLA-DRB1*10:01 allele.1 Brain MRI, thoracoabdominal CT, whole-body FDG-PET, and video-polysomnography were unremarkable. No sleep disturbances, bulbar symptoms, parkinsonism, or dementia were detected. Intravenous methylprednisolone (500 mg/d for 5 days), followed by oral benzodiazepines, prompted rapid functional recovery, with limb stiffness and gait improvement (Video 1), which persisted at 6-month follow-up. Anti-IgLON5 disease has progressive course and protean clinical presentations,2 representative, in our patient, for overlapping signs and symptoms of neuromuscular hyperexcitability and rigidity. Identification of rare phenotypes is important because prompt recognition and treatment can improve prognosis.

Successful Treatment of Post COVID-19 Neurogenic Dysphagia with Botulinum Toxin.

Introduction: Dysphagia in post COVID-19 patients could be caused by several factors, including reduced pharyngolaryngeal coordination due to SARS-CoV-2 tropism to the central and/or peripheral nervous system. To our knowledge, this is the first reported case of COVID-19-related dysphagia successfully treated with botulinum toxin type A injection. Case description: We report the case of a patient with severe oropharyngeal dysphagia due to COVID-19 confirmed by fibre endoscopy. As a result, the patient required an enteral feeding tube. After two months of traditional swallowing therapies, there was only limited improvement. An electrophysiologic evaluation of the cricopharyngeal muscle was performed and showed a normal inhibition of the cricopharyngeal muscle, followed by a hypertonic rebound. Based on this result, we decided to perform a unilateral laryngeal injection of botulinum toxin type A. After the injection, the patient's swallowing function improved significantly, allowing him to return to oral feeding. Discussion: Newly diagnosed oropharyngeal dysphagia was found in 35.3% of hospitalised patients with COVID-19. There are several possible causes of COVID-19-associated dysphagia, including stroke, encephalitis, critical illness neuropathy, Guillain-Barré syndrome and skeletal muscle injury. In our case, since stroke was excluded by brain MRI, cranial nerve injury was a possible explanation for the difficult recovery of swallowing despite daily swallowing therapy. Conclusion: We suggest that electrophysiology is a valid tool for the diagnosis and follow-up of patients with oropharyngeal dysphagia. LEARNING POINTS: SARS-CoV-2 tropism to the central and/or peripheral nervous system can cause dysphagia in post COVID-19 patients.An electrophysiologic approach is useful for the diagnosis and follow-up of patients with oropharyngeal dysphagia.A single botulinum toxin type A injection is a valid treatment option to improve the swallowing function in patients with post COVID-19 dysphagia.

A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials.

Background: Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. Methods: As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Findings: Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)-thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. Interpretation: There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence. Funding: SPIRIT-SURROGATE/CONSORT-SURROGATE project is Medical Research Council Better Research Better Health (MR/V038400/1) funded.

Tagging EEG features within exam reports to quickly generate databases for research purposes.

OBJECTIVE: assess the effectiveness of a new method for classifying EEG recording features through the use of tags within reports. We present feature prevalence in a sample of patients with toxic-metabolic encephalopathy and discuss the advantages of this approach over existing classification systems. METHODS: during EEG report creation, tags reflecting background activity, epileptiform features and periodic discharges were selected according to the findings of each recording. Reports including the tags have been collected and processed by the EEG report parser script written in PHP language. The resulting spreadsheet was analysed to calculate the prevalence and type of EEG features in a sample group of patients with toxic-metabolic encephalopathy. RESULTS: tag checking and extraction were very little time-consuming processes. Considering 5784 EEG recordings performed either in inpatients or outpatients over 2 years, toxic-metabolic aetiology was tagged in 218 (3.8 %). The most frequent background feature was severe slowing (5-6 Hz frequency), occurring in 79 (36.2 %). Epileptiform abnormalities were rare, reaching a maximum of 10 (4.6 %). Triphasic waves were tagged in 43 (19.7 %) recordings. CONCLUSIONS: tagging and parsing processes are very fast and integrated into the daily routine. Sample analysis in patients with toxic-metabolic encephalopathies showed EEG slowing as the prevalent feature, while triphasic waves occurred in a minority of recordings. Existing software such as "SCORE" (Holberg EEG) requires the replacement of the currently used software for EEG reporting, minimizing additional costs and training. EEG Report Parser is free and open-source software, so it can be freely adopted, modified and redistributed, allowing further improvement and adaptability.

Neuromodulation-induced prehabilitation to leverage neuroplasticity before brain tumor surgery: a single-cohort feasibility trial protocol.

Introduction: Neurosurgery for brain tumors needs to find a complex balance between the effective removal of targeted tissue and the preservation of surrounding brain areas. Neuromodulation-induced cortical prehabilitation (NICP) is a promising strategy that combines temporary inhibition of critical areas (virtual lesion) with intensive behavioral training to foster the activation of alternative brain resources. By progressively reducing the functional relevance of targeted areas, the goal is to facilitate resection with reduced risks of neurological sequelae. However, it is still unclear which modality (invasive vs. non-invasive neuromodulation) and volume of therapy (behavioral training) may be optimal in terms of feasibility and efficacy. Methods and analysis: Patients undertake between 10 and 20 daily sessions consisting of neuromodulation coupled with intensive task training, individualized based on the target site and neurological functions at risk of being compromised. The primary outcome of the proposed pilot, single-cohort trial is to investigate the feasibility and potential effectiveness of a non-invasive NICP protocol on neuroplasticity and post-surgical outcomes. Secondary outcomes investigating longitudinal changes (neuroimaging, neurophysiology, and clinical) are measured pre-NICP, post-NICP, and post-surgery. Ethics and dissemination: Ethics approval was obtained from the Research Ethical Committee of Fundació Unió Catalana d'Hospitals (approval number: CEI 21/65, version 1, 13/07/2021). The results of the study will be submitted to a peer-reviewed journal and presented at scientific congresses. Clinical trial registration: ClinicalTrials.gov, identifier NCT05844605.

Effectiveness of a Preventative Program for Groin Pain Syndrome in Elite Youth Soccer Players: A Prospective, Randomized, Controlled, Single-Blind Study.

Groin pain syndrome (GPS) is a prevalent issue in soccer. This study assessed the effectiveness of a new preventive protocol on GPS for youth soccer players. The protocol included targeted stretching and strengthening exercises for the adductor and core muscles from preseason to midseason. A questionnaire and two pain provocation tests were used for the evaluation. Mild GPS required positive results in at least two evaluations, while severe GPS was associated with pain incompatible with engagement in any activity confirmed by diagnostic ultrasound. Forty-two elite male athletes (aged 16.9 ± 0.7 years) participated in the study, with half of them assigned to the usual training (control group) and the remaining athletes undergoing the preventive protocol (treatment group) for 24 weeks. GPS rates were 14.3% (three diagnoses: two mild, one severe) in the treatment group and 28.6% (six diagnoses: three mild, three severe) in the control group. Toward the end of the season, three players, one from the treatment group and two from the control group had to stop playing due to severe GPS problems. In addition, one player in the control group stopped midseason. Even though the reduction in the risk of developing GPS was not significant (relative risk of 0.50 ([95%CI 0.14 to 1.74], p = 0.2759), the halved incidence of severe GPS and the increased muscle strength related to the treatment (p = 0.0277) are encouraging data for future studies.

Young para-athletes display more hedonic well-being than people with disabilities not taking part in competitive sports: insights from a multi-country survey.

Hedonic well-being relates to how individuals experience and rate their lives. People with disabilities due to their pathology may more frequently suffer from anxiety and depressive disorders than their able-bodied counterparts. Sports participation is an essential way to cope with disability. On the other hand, compared with their able-bodied peers, para-athletes undergo a unique series of stressors. Little is known in terms of hedonic well-being in this specific population. We present the results of a multi-country survey of self-perceived hedonic well-being by para-athletes of different sports disciplines and a control group (disabled individuals not playing competitive sports), using the "Psychological General Well-Being Index" (PGWBI). We included 1,208 participants, aged 17.39 years, 58.4% male, 41.6% female, and 70.3% para-athletes. Para-athletes exhibited higher well-being than disabled people, for all domains of the PGWBI scale. The nature of disability/impairment was significant, with those with acquired disability reporting lower well-being. Those taking part in wheelchair basketball, para-athletics, and para-swimming competitions had a higher likelihood of reporting well-being, whereas those engaged in wheelchair rugby exhibited lower well-being compared with controls. This large-scale investigation can enable a better understanding of the self-perceived hedonic well-being of disabled people.

Increasing the Passive Range of Joint Motion in Stroke Patients Using Botulinum Toxin: The Role of Pain Relief.

By blocking the release of neurotransmitters, botulinum toxin A (BoNT-A) is an effective treatment for muscle over-activity and pain in stroke patients. BoNT-A has also been reported to increase passive range of motion (p-ROM), the decrease of which is mainly due to muscle shortening (i.e., muscle contracture). Although the mechanism of action of BoNT-A on p-ROM is far from understood, pain relief may be hypothesized to play a role. To test this hypothesis, a retrospective investigation of p-ROM and pain was conducted in post-stroke patients treated with BoNT-A for upper limb hypertonia. Among 70 stroke patients enrolled in the study, muscle tone (Modified Ashworth Scale), pathological postures, p-ROM, and pain during p-ROM assessment (Numeric Rating Scale, NRS) were investigated in elbow flexors (48 patients) and in finger flexors (64 patients), just before and 3-6 weeks after BoNT-A treatment. Before BoNT-A treatment, pathological postures of elbow flexion were found in all patients but one. A decreased elbow p-ROM was found in 18 patients (38%). Patients with decreased p-ROM had higher pain-NRS scores (5.08 ± 1.96, with a pain score ≥8 in 11% of cases) than patients with normal p-ROM (0.57 ± 1.36) (p < 0.001). Similarly, pathological postures of finger flexion were found in all patients but two. A decreased finger p-ROM was found in 14 patients (22%). Pain was more intense in the 14 patients with decreased p-ROM (8.43 ± 1.74, with a pain score ≥ 8 in 86% of cases) than in the 50 patients with normal p-ROM (0.98 ± 1.89) (p < 0.001). After BoNT-A treatment, muscle tone, pathological postures, and pain decreased in both elbow and finger flexors. In contrast, p-ROM increased only in finger flexors. The study discusses that pain plays a pivotal role in the increase in p-ROM observed after BoNT-A treatment.

The role of cerebellum in timing processing: A contingent negative variation study.

Time management is an important aspect of human behaviour and cognition. Several brain regions are thought to be involved in motor timing and time estimation tasks. However, subcortical regions such as the basal nuclei and cerebellum seem to play a role in timing control. The aim of this study was to investigate the role of the cerebellum in temporal processing. For this purpose, we transitorily inhibited cerebellar activity by means of cathodal transcranial direct current stimulation (tDCS) and studied the effects of this inhibition on contingent negative variation (CNV) parameters elicited during a S1-S2 motor task in healthy subjects. Sixteen healthy subjects underwent a S1-S2 motor task prior to and after cathodal and sham cerebellar tDCS in separate sessions. The CNV task consisted of a duration discrimination task in which subjects had to determine whether the duration of a probe interval trial was shorter (800 ms), longer (1600 ms), or equal to the target interval of 1200 ms. A reduction in total CNV amplitude emerged only after cathodal tDCS for short and target interval trials, while no differences were detected for the long interval trial. Errors were significantly higher after cathodal tDCS than at baseline evaluation of short and target intervals. No reaction time differences were found for any time interval after the cathodal and sham sessions. These results point to a role of the cerebellum in time perception. In particular, the cerebellum seems to regulate temporal interval discrimination for second and sub-second ranges.

A Scoping Review with Bibliometric Analysis of Para-Rowing: State of the Art and Future Directions.

Para-rowing is a format of rowing practiced by people with different types of disabilities, thanks to adapted equipment set-ups and regulations. Para-rowing made its debut recently at the 2008 Paralympic Games. According to the mandate of the "International Paralympic Committee", para-rowers should be enabled to pursue sporting excellence. Therefore, rigorous research is needed in terms of well-designed, high-quality studies. To the best of our knowledge, there are no systematic appraisals of the body of scholarly evidence in the field of para-rowing. As such, a scoping review enhanced by bibliometric analyses was carried out to provide a comprehensive synthesis of knowledge related to para-rowing for the perusal of practitioners and athletes. By mining eighteen major databases, 17 studies were retained in the present review. The included studies were found to focus on a range of aspects involving health, the etiology of injuries (n = 5), psychological and physiological responses (n = 5), performance, biomechanical analysis (n = 4), and new analytical approaches for kinematic assessments and predictions of mechanical outputs in para-rowers (n = 3). The scholarly community on para-rowing consists of 78 researchers, 16 (20.51%) of whom are highly interconnected. The most prolific author was Smoljanovic T., from Croatia, with three items/documents. In total, 93.6% of scholars have authored one single document. Topological features indicated a highly fragmented and dispersed, poorly connected community characterized by a high number of clusters and a low strength of connections. In terms of publication years, the first scholarly article dates back to 2008, with four articles (23.5%) published in the current year, showing an increasing interest in this para-sports discipline. Finally, gaps in current research on para-rowing were identified in terms of overlooked topics, including sports nutrition, doping, and psychological aspects in para-rowers other than those with visual impairment.

Actigraphic Sensors Describe Stroke Severity in the Acute Phase: Implementing Multi-Parametric Monitoring in Stroke Unit.

Actigraphy is a tool used to describe limb motor activity. Some actigraphic parameters, namely Motor Activity (MA) and Asymmetry Index (AR), correlate with stroke severity. However, a long-lasting actigraphic monitoring was never performed previously. We hypothesized that MA and AR can describe different clinical conditions during the evolution of the acute phase of stroke. We conducted a multicenter study and enrolled 69 stroke patients. NIHSS was assessed every hour and upper limbs' motor activity was continuously recorded. We calculated MA and AR in the first hour after admission, after a significant clinical change (NIHSS ± 4) or at discharge. In a control group of 17 subjects, we calculated MA and AR normative values. We defined the best model to predict clinical status with multiple linear regression and identified actigraphic cut-off values to discriminate minor from major stroke (NIHSS ≥ 5) and NIHSS 5-9 from NIHSS ≥ 10. The AR cut-off value to discriminate between minor and major stroke (namely NIHSS ≥ 5) is 27% (sensitivity = 83%, specificity = 76% (AUC 0.86 p < 0.001), PPV = 89%, NPV = 42%). However, the combination of AR and MA of the non-paretic arm is the best model to predict NIHSS score (R2: 0.482, F: 54.13), discriminating minor from major stroke (sensitivity = 89%, specificity = 82%, PPV = 92%, NPV = 75%). The AR cut-off value of 53% identifies very severe stroke patients (NIHSS ≥ 10) (sensitivity = 82%, specificity = 74% (AUC 0.86 p < 0.001), PPV = 73%, NPV = 82%). Actigraphic parameters can reliably describe the overall severity of stroke patients with motor symptoms, supporting the addition of a wearable actigraphic system to the multi-parametric monitoring in stroke units.

Mal de Debarquement Syndrome explained by a vestibulo-cerebellar oscillator.

Mal de Debarquement Syndrome (MdDS) is a puzzling central vestibular disorder characterized by a long-lasting perception of oscillatory postural instability that may occur after sea travels or flights. We have postulated that MdDS originates from the post-disembarking persistence of an adaptive internal oscillator consisting of a loop system, involving the right and left vestibular nuclei, and the Purkinje cells of the right and left flocculonodular cerebellar cortex, connected by GABAergic and glutamatergic fibers. We have formulated here a mathematical model of the vestibulo-cerebellar loop system and carried out a computational analysis based on a set of differential equations describing the interactions among the loop elements and containing Hill functions that model input-output firing rates relationships among neurons. The analysis indicates that the system acquires a spontaneous and permanent oscillatory behavior for a decrease of threshold and an increase of sensitivity in neuronal input-output responses. These results suggest a role for synaptic plasticity in MdDS pathophysiology, thus reinforcing our previous hypothesis that MdDS may be the result of excessive synaptic plasticity acting on the vestibulo-cerebellar network during its entraining to an oscillatory environment. Hence, our study points to neuroendocrine pathways that lead to increased synaptic response as possible new therapeutic targets for the clinical treatment of the disorder.

Skeletal muscle involvement in biallelic SORD mutations: case report and review of the literature.

Biallelic mutations in the sorbitol dehydrogenase (SORD) gene have been identified as a genetic cause of autosomal recessive axonal Charcot-Marie-Tooth disease 2 (CMT2) and distal hereditary motor neuropathy (dHMN). We herein review the main phenotypes associated with SORD mutations and report the case of a 16-year-old man who was referred to our outpatient clinic for a slowly worsening gait disorder with wasting and weakness of distal lower limbs musculature. Since creatine phosphokinase (CPK) values were persistently raised (1.5fold increased) and a Next-Generation Sequencing CMT-associated panel failed in identifying pathogenic variants, a muscle biopsy was performed with evidence of alterations suggestive of a protein surplus distal myopathy. Finally, Whole-Exome Sequencing (WES) identified two pathogenic SORD variants in the heterozygous state: c.458C > A (p.Ala153Asp) and c.757delG (p.Ala253Glnfs*27). This is an isolated report of compound heterozygosity for two SORD mutations associated with clinical and histological signs of skeletal muscle involvement, expanding the phenotypic expression of SORD mutations.

Respiratory involvement and sleep-related disorders in CMT1A: case report and review of the literature.

Sleep-disordered breathing has been reported in Charcot-Marie-Tooth disease (CMT) type 1A in association with diaphragmatic weakness and sleep apnea syndrome, mainly of the obstructive type (OSA). Improvement has been observed not only in sleep quality but also in neuropathy symptoms in CMT1A patients with OSA following the initiation of continuous positive airway pressure. We report the cases of two siblings affected by CMT1A associated with hemidiaphragm relaxatio necessitating nocturnal non-invasive ventilation (NIV). Two twins, now 42 years old, with a family history of CMT1A, received a genetic diagnosis of CMT1A at the age of 16. Over the years, they developed a slowly worsening gait disorder and a decline in fine motor hand movements, currently presenting with moderate disability (CMTES:13). At the age of 40, they both started complaining of daytime sleepiness, orthopnea, and exertional dyspnea. They received a diagnosis of relaxatio of the right hemidiaphragm associated with impairment of nocturnal ventilation and they both have benefited from nocturnal NIV. Disorders of breathing during sleep may be underestimated in CMT1A since routine investigations of sleep quality are rarely performed. Our two clinical cases and a literature review suggest the importance of inquiring about symptoms of excessive daytime sleepiness and respiratory disturbances in individuals with CMT1A, even in the absence of severe neuropathy. In the presence of compatible symptoms, a pneumological assessment, along with an overnight polysomnogram and lung function tests, should be performed. Recognizing sleep-related symptoms is essential for providing accurate treatment and improving the quality of life for patients with CMT1A.

The Effect of Verbal Encouragement on Performance and Muscle Fatigue in Swimming.

Background and Objectives: Verbal encouragement (VE) can be used to enhance performance in several sports, even though no studies have been conducted among swimmers and only a few effects have been reported in elite athletes. Besides influencing motor performance, VE is also known to enhance the physical load, thus potentially increasing the probability of developing fatigue. With this in mind, this study aimed to explore the effects of VE in swimmers in order to fill in the knowledge gap concerning the aquatic environment. Materials and Methods: Each athlete swam a maximal 200 m freestyle trial under two different conditions: one trial with VE and the other without VE. The two main outcome measures were: (1) performance velocity (m/s); and (2) muscle fatigue, investigated by means of surface electromyography. Sixty swimmers were recruited, aged 18.63 ± 3.46 years (median 18 years), 28 men (47%), and 32 women (53%), with 7.03 ± 3.9 years of experience. Results: With VE, performance significantly improved in the swim trial (p < 0.001, effect size (ES) −0.95, large). When breaking the results down into the first half (first (0−100 m) vs. the second half (100−200 m)), the ES was large in the first part (−1.11), indicating an improvement in performance. This worsened, however, in the second part of the trial (ES 0.63). In the multivariate analysis, years of experience were found to be a significant predictor of the change in overall performance (p = 0.011). There was a significant increase in muscle fatigue induced by VE, overall, and during the second half, but not during the first half of the trial. Conclusions: The present study indicates that VE during a middle-distance event (200 m) increases performance most in swimmers with little experience. However, it has a negative impact on fatigue.

Planetary sleep medicine: Studying sleep at the individual, population, and planetary level.

Circadian rhythms are a series of endogenous autonomous oscillators that are generated by the molecular circadian clock which coordinates and synchronizes internal time with the external environment in a 24-h daily cycle (that can also be shorter or longer than 24 h). Besides daily rhythms, there exist as well other biological rhythms that have different time scales, including seasonal and annual rhythms. Circadian and other biological rhythms deeply permeate human life, at any level, spanning from the molecular, subcellular, cellular, tissue, and organismal level to environmental exposures, and behavioral lifestyles. Humans are immersed in what has been called the "circadian landscape," with circadian rhythms being highly pervasive and ubiquitous, and affecting every ecosystem on the planet, from plants to insects, fishes, birds, mammals, and other animals. Anthropogenic behaviors have been producing a cascading and compounding series of effects, including detrimental impacts on human health. However, the effects of climate change on sleep have been relatively overlooked. In the present narrative review paper, we wanted to offer a way to re-read/re-think sleep medicine from a planetary health perspective. Climate change, through a complex series of either direct or indirect mechanisms, including (i) pollution- and poor air quality-induced oxygen saturation variability/hypoxia, (ii) changes in light conditions and increases in the nighttime, (iii) fluctuating temperatures, warmer values, and heat due to extreme weather, and (iv) psychological distress imposed by disasters (like floods, wildfires, droughts, hurricanes, and infectious outbreaks by emerging and reemerging pathogens) may contribute to inducing mismatches between internal time and external environment, and disrupting sleep, causing poor sleep quantity and quality and sleep disorders, such as insomnia, and sleep-related breathing issues, among others. Climate change will generate relevant costs and impact more vulnerable populations in underserved areas, thus widening already existing global geographic, age-, sex-, and gender-related inequalities.