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Background This study aimed to assess the added value and current applications of SWI in the diagnosis of pediatric non-neoplastic neurological diseases, including its ability to characterize hemorrhage in various brain lesions and its important role in the evaluation of both arterial as well as venous ischemic brain lesions. Results Forty pediatric patients with a median age of 9 years were included in our prospective study; 23 were males and 17 females. SWI had a significantly higher detection rate than conventional MRI for traumatic brain injury (TBI) lesions, hemorrhagic lesions in acute necrotizing encephalopathy (ANEC), and cavernoma lesions (p = 0.005, p = 0.038, and p = 0.046, respectively). The sensitivity, specificity and accuracy of SWI for the detection of venous ischemic insult was 88.9%, 50%, and 76.9% respectively. SWI was significantly better than the conventional MRI (p = 0.046) for the detection of chronic ischemic brain insults and ischemic lesions with added hemorrhagic components. Conclusion SWI is a technique with reasonable acquisition time that could improve the diagnostic performance of MRI for the evaluation of various pediatric non-neoplastic neurological diseases.

Background: Chorea is recognized as a prototypic motor feature of Huntington’s disease (HD), but its effect on health-related quality of life (HRQoL) has not been fully explored. This study describes the impact of chorea on HRQoL in patients with HD. Objective: To determine the impact of HD-related chorea on employment, self-care activities, activities of daily living, and health-care resource utilization (HCRU). Methods: Data were drawn from the Adelphi HD Disease Specific Programme, a real-world point-in-time survey of 144 neurologists and 427 patients in the United States between July and October 2017. HD patients with and without chorea were identified and examined for differences in employment status, reasons for employment changes, self-care activities, and modifications to cope with involuntary movements. Bivariate tests and inverse probability weighted regression adjustment methods were used to determine differences in outcomes between patients with and without chorea. Results: HD patients with (n=287) and without (n=140) chorea were identified. Patients with chorea were less likely to be employed full-time (16.7% vs 25.7%; PPPPP Discussion: These results demonstrate that HD patients with chorea experienced greater negative impact to employment, self-care activities, and HCRU than patients without chorea experienced. These patients were more likely to stop working due to motor, cognitive, and behavioral symptoms; require modifications in the home and workplace; and need more assistance from caregivers than patients without chorea. Conclusions: Patients with HD-related chorea have greater detriments to emotional, interpersonal, and professional functioning that could be improved by reducing chorea.

**Objectives:** We developed a Markov model to simulate a treatment flow of epilepsy patients who refer to specialized care from non-specialized care, and to surgery from specialized care for estimation of patient distributions and expenditures caused by increasing the referral rate for specialized care. **Methods:** This budget impact analysis of treatment flow optimization in epilepsy patients was performed as a long-term simulation using the Markov model by comparing the current treatment flow and the optimized treatment flow. In the model, we simulated the prognosis of new onset 5-year-old epilepsy patients (assuming to represent epilepsy occurring between 0 and 10 years of age) treated over a lifetime period. Direct costs of pharmacotherapies, management fees and surgeries are included in the analysis to evaluate the annual budget impact in Japan. **Results:** In the current treatment flow, the number of refractory patients treated with four drugs by non-specialized care were estimated as 8766 and yielded JPY5.8 billion annually. However, in the optimized treatment flow, the number of patients treated with four drugs by non-specialized care significantly decreased and who continued the monotherapy increased. The costs for the four-drug therapy by non-specialized care were eliminated. Hence cost-saving of JPY9.5 billion (-5% of the current treatment flow) in total national expenditures would be expected. **Conclusion:** This study highlights that any policy decision-making for referral optimization to specialized care in appropriate epilepsy patients would be feasible with a cost-savings or very few budget impacts. However, important information in the decision-making such as transition probability to the next therapy or excuse for sensitive limitations is not available currently. Therefore, further research with reliable data such as big data analysis or a national survey with real-world treatment patterns is needed.

Organ transplantation is the ultimate treatment for end-stage diseases such as heart and liver failure. However, the severe shortage of donor organs has limited the organ transplantation progress. Xenogeneic stem cell transplantation provides a new strategy to solve this problem. Researchers have shown that xenogeneic stem cell transplantation has significant therapeutic effects and broad application prospects in treating liver failure, myocardial infarction, advanced type 1 diabetes mellitus, myelosuppression, and other end-stage diseases by replacing the dysfunctional cells directly or improving the endogenous regenerative milieu. In this review, the sources, problems and solutions, and potential clinical applications of xenogeneic stem cell transplantation will be discussed.

**Background:** Nonadherence to medication is prevalent in persons diagnosed with schizophrenia, thus increasing the likelihood of relapse, poor health outcomes, hospitalization, high treatment costs, and high rates of both violent and non-violent offenses. **Objective:** To assess the association between long-acting injectable (LAI) antipsychotic use and criminal justice system encounters in patients with schizophrenia or schizoaffective disorder. **Methods:** This retrospective follow-up study was conducted among patients aged ≥18 years treated for schizophrenia or schizoaffective disorder at a community mental health center in Akron, Ohio, between January 1, 2010, and June 15, 2016. The incidence of criminal justice system encounters at 6 months, 1 year, and 2 years pre- versus post-LAI antipsychotic initiation was assessed. A subanalysis was conducted for individuals with a history of prior arrest. **Results:** Overall, the risk ratio (RR) of having an encounter with the criminal justice system was significantly lower for patients treated with LAI antipsychotics 1 year after initiation of treatment compared with a similar time period prior to initiation (RR \[95% confidence interval (CI)\]: 0.74 \[0.59–0.93\]; *P*

Severe neurodegenerative diseases such as Parkinson's disease or multiple sclerosis and acute events like stroke, spinal cord injuries, or other related pathologies have been shown to negatively impact the central and peripheral nervous systems, thus causing severe impairments to mobility. The development and utilization of exoskeletons as rehabilitation devices have shown good potential for improving patients' gait function. Ten older adults (age: 68.9 ± 9.2 yrs; height: 1.65 ± 0.08 m; mass: 71.6 ± 11.0 kg) affected by neurological diseases impacting their gait function completed a 10-session gait training protocol where they walked for 10 minutes wearing a passive exoskeleton assisting hip flexion, namely, Exoband. Results showed that participants walked a significantly longer distance in the last session of training with respect to the first session (453.1 ± 178.8 m vs 392.4 ± 135.1 m, respectively). This study indicates the potential of Exoband as an effective tool for gait rehabilitation in patients with neurological diseases. Wearable, lightweight, and low-cost devices such as the one involved in this work have the potential to improve walking distance in patients.

Infodemiology is a research discipline that investigates parameters of information distribution in order to support public health and public policy. Wikipedia, a free online encyclopedia, is commonly used as a source of information for infodemiological studies. Using Pageviews analysis, we descriptively assessed the total monthly number of views of the Wikipedia articles in English describing main neurological diseases in the period from January 2018 to July 2020. Our results show a general trend of a decrease in interest in neurological disease-related pages throughout years and especially during the burst of interest towards coronavirus. The monitoring of infodemiological indicators shall be prioritized to reshape global campaigns and tailored advocacy programs.

The COVID‐19 pandemic is a global public health issue. Neurological complications have been reported in up to one‐third of affected cases, but their distribution varies significantly in terms of prevalence, incidence and phenotypical characteristics. Variability can be mostly explained by the differing sources of cases (hospital vs. community‐based), the accuracy of the diagnostic approach, and the interpretation of the patients’ complaints. Moreover, after recovering, patients can still experience neurological symptoms. To obtain a more precise picture of the neurological manifestations and outcome of the COVID‐19 infection, an international registry (ENERGY) has been created by the European Academy of Neurology (EAN) in collaboration with European national neurological societies and the Neurocritical Care Society and Research Network (NCRN). ENERGY can be implemented as a stand‐alone instrument for patients with suspected or confirmed COVID‐19 patients AND neurological findings or as an addendum to an existing registry not targeting neurologic symptoms. Data are also collected to study the impact of neurological symptoms and neurological complications on outcomes. The variables included in the registry have been selected in the interest of most countries, to favour pooling with data from other sources, and to facilitate data collection even in resource‐poor countries. Included are adults with suspected or confirmed COVID‐19 infection, ascertained through neurological consultation, and providing informed consent. Key demographic and clinical findings are collected at registration. Patients are followed up to 12 months in search of incident neurological manifestations. As of August 19, 254 centres from 69 countries and four continents have made requests to join the study.

COVID-19 may increase the risk of heat-related symptoms during hot weather since vulnerable populations, including the elderly and those with neurological disabilities, must continue to self-isolate, often indoors. Within the chronic neurological patient population, indoor conditions in summer months present a hazard because of impaired and/or altered thermoregulation, including poor hydration status due to both autonomic and behavioral dysfunction(s). To address this increased risk, telemedicine protocols should include an assessment of the patient's environmental parameters, and when combined with physiological data from wearable devices, identify those with neurological diseases who are at higher risk of heat illness. Personalized medicine during times of self-isolation must be encouraged, and using smart technology in ambient assisted living solutions, including e-health to monitor physiological parameters are highly recommended, not only during extreme weather conditions but also during times of increased isolation and vulnerability.

Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by HPLC-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal-appearing white matter (NAWM) of the normal CNS (nCNS) from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from the nCNS and active MS (Ac-MS) lesions. Chronic inactive MS (In-MS) lesions were characterized by decreased levels of dihydroceramide (dhCer), ceramide (Cer), and SM subspecies, whereas levels of hexosylceramide and Cer 1-phosphate (C1P) subspecies were significantly increased in comparison to NAWM of the nCNS as well as Ac-MS plaques. In contrast, Ac-MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of the nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stages of MS. Moreover, they suggest that C1P could be a new biomarker of the In-MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease.

Supplemental digital content is available in the text., Objective Neurological nosology, based on categorical systems, has largely ignored dimensional aspects of neurocognitive impairments. Transdiagnostic dimensional approaches of interoception (the sensing of visceral signals) may improve the descriptions of cross-pathological symptoms at behavioral, electrophysiological, and anatomical levels. Alterations of cardiac interoception (encompassing multidimensional variables such as accuracy, learning, sensibility, and awareness) and its neural correlates (electrophysiological markers, imaging-based anatomical and functional connectivity) have been proposed as critical across disparate neurological disorders. However, no study has examined the specific impact of neural (relative to autonomic) disturbances of cardiac interoception or their differential manifestations across neurological conditions. Methods Here, we used a computational approach to classify and evaluate which markers of cardiac interoception (behavioral, metacognitive, electrophysiological, volumetric, or functional) offer the best discrimination between neurological conditions and cardiac (hypertensive) disease (model 1), and among neurological conditions (Alzheimer’s disease, frontotemporal dementia, multiple sclerosis, and brain stroke; model 2). In total, the study comprised 52 neurological patients (mean [standard deviation] age = 55.1 [17.3] years; 37 women), 25 cardiac patients (age = 66.2 [9.1] years; 13 women), and 72 healthy controls (age = 52.65 [17.1] years; 50 women). Results Cardiac interoceptive outcomes successfully classified between neurological and cardiac conditions (model 1: >80% accuracy) but not among neurological conditions (model 2: 53% accuracy). Behavioral cardiac interoceptive alterations, although present in all conditions, were powerful in differentiating between neurological and cardiac diseases. However, among neurological conditions, cardiac interoceptive deficits presented more undifferentiated and unspecific disturbances across dimensions. Conclusions Our result suggests a diffuse pattern of interoceptive alterations across neurological conditions, highlighting their potential role as dimensional, transdiagnostic markers.

Background To study the association between sleep quality and oral health related variables, which still have conflicts in the literature. Material and Methods This was a population-based case-control study between subjects with versus without sleep disorders from the Brazilian Public Health System (SUS), city of Maringá (N=1,643). Subjects answered self-reported questionnaires: a) Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), b) Sleep Assessment Questionnaire (SAQ) and c) North York Dental Health Survey (NYDHS). Results No significant difference was found for gender, marital status, or income; however, non-Caucasians, people with lower levels of education, and those between 20 to 50 years old had worse scores of sleep disorders in the SAQ. Self-perceived oral health, masticatory capacity to eat foods, and gingival bleeding was significantly worse among subjects with self-reported sleep disorders. Self-reported tooth loss, edentulism and use of removable partial dentures (with clasps) or complete dentures showed no significant difference between groups. Self-reported sleep disorder subjects presented significantly higher prevalence of both self-reported tooth and TMJ pain. Conclusions It can be concluded that individuals with self-reported sleep disorders presented worse self-perceived oral health for most studied variables. Key words:Oral health, case control study, sleep; review, gingivitis, periodontitis, tooth loss.

The 5th International Porto Congress of Multiple Sclerosis took place between the 14th and 16th of February 2019 in Porto, Portugal. Its intensive programme covered a wide-range of themes—including many of the hot topics, challenges, pitfalls and yet unmet needs in the field of multiple sclerosis (MS)—led by a number of well-acknowledged world experts. This meeting review summarizes the talks that took place during the congress, which focussed on issues in MS as diverse as the development and challenges of progressive MS, epidemiology, differential diagnosis, medical management, molecular research and imaging tools.

Dysphagia is defined as an impairment of this complex and integrated sensorimotor system. It is estimated that 400,000 to 800,000 individuals worldwide develop neurogenic dysphagia per year. Neurogenic dysphagia is typically occurring in patients with neurological disease of different etiologies. A correct and early diagnosis and an appropriate management of dysphagia could be useful for improving patient’s quality of life and may help to prevent or delay death. In the present review, we discuss thoroughly the anatomy and physiology of swallowing and also the pathophysiological mechanisms involved in impaired swallowing, as well as the diagnosis, management, and potential treatments of neurogenic dysphagia. Assessment of neurogenic dysphagia includes medical history, physical exam, and instrumental examinations (fiberoptic endoscopic evaluation of swallowing, videofluoroscopic swallowing study, electromyography). Pharmacological treatment of these problems includes oral anticholinergic drugs. Surgical myotomy of the cricopharyngeal muscle showed an important improvement of oropharyngeal dysphagia associated to upper esophageal sphincter hyperactivity. Chemical myotomy of the upper esophageal sphincter by local injections of botulinum toxin type A into the cricopharyngeal muscle has been proposed as an alternative less invasive and less unsafe than surgical myotomy.

In this study, a 1.1 MW diesel-gen-set is used to design a Waste Heat Recovery (WHR) system to generate additional power using Rankine cycle (RC). A computer code is written in commercial Engineering Equation Solver (EES) software to solve equations of overall energy and mass balance, heat transfer, evaporation, condensation, frictional and heat losses for heat exchangers, turbine, pumps, cooling tower and connecting pipes connecting different components. After initial design of the WHR system, manufacturers are contacted to find out the availability of parts, and then, accordingly the design is changed. There are several heat exchangers required to heat the water from liquid to super heated steam and then, it is passed to the turbine. Then, after the expansion in the turbine, it is passed to the condenser to condense the steam to water. Optimization is done on the heat exchangers, focusing on the tube length and diameter. The tube length is changed in accordance to the availability on the market, where it comes in 2 m length. At the rated power of the gen-set, with a pressure ratio of 100 (inlet and outlet pressures to the turbine are 30 bar and 0.3 bar, respectively), an overall improvement of 12.2% is achieved. Results from this study can be applied to large diesel engines used for large trucks which fall in the USA commercial truck category of Class 7 and 8 of heavy trucks, large diesel-gen-set and mobile applications such as ships, heavy construction equipment, ultra-heavy mining movers, excavators and locomotives. It found that the WHR system could be as heavy as the gen-set and they are bulky. Therefore, not only the overall efficiency improvement is important, the size and weight of the WHR system is also very important. Refereed/Peer-reviewed

Learning motor skills is an essential part of most rehabilitation processes. Facilitating and supporting motor learning is particularly challenging in neurological rehabilitation: patients who suffer from neurological diseases experience both physical limitations and difficulties of cognition and communication that affect and/or complicate the motor learning process. Therapists (e.g. physiotherapists and occupational therapists) who work in neurorehabilitation are therefore continuously searching for the best way to facilitate patients during these intensive learning processes. To support therapists in the application of motor learning, a framework was developed, integrating knowledge from the literature and the opinions and experiences of international experts. This article presents the framework, illustrated by cases from daily practice. The framework may assist therapists working in neurorehabilitation in making choices, implementing motor learning in routine practice, and supporting communication of knowledge and experiences about motor learning with colleagues and students. The article discusses the framework and offers suggestions and conditions given for its use in daily practice.

International audience; The transfer of adolescents from paediatric care to adult health facilities is often difficult for the patients and their families and can lead to a breakdown in medical follow-up and therefore serious complications. Existing recommendations for the successful transition of patients with chronic disorders do not specifically address patients with handicap. Preparations for the transfer must be made well in advance. They must aim to achieve the autonomisation of adolescents by making them responsible and providing them with the knowledge that will enable them to manage their care themselves, the know-how to react appropriately if there is any change in their condition, and to move comfortably within the adult health system. This requires the active participation of the patient, his or her family and the paediatric and adult care teams. It involves multidisciplinary management plus the production and maintenance of an educational therapy programme. Finally, the identification of doctors trained in handicap, relevant sub-specialists and even expert patients could enable improvements in the continuum of complete and appropriate care for these patients within adult medicine.

The neurological devastation of neurodegenerative and cerebrovascular diseases reinforces our perseverance to find advanced treatments to deal with these fatal pathologies. High-performance preclinical results have failed at clinical level, as it has been the case for a wide variety of neuroprotective agents and cell-based therapies employed to treat high prevalent brain pathologies such as stroke, Alzheimer’s and Parkinson’s diseases. An unquestionable reality is the current absence of effective therapies to neuroprotect the brain, to arrest neurodegeneration and rewire the impaired brain circuits. Part of the problem might arise from the lack of adequate in vitro and in vivo models and that most of the underlying pathophysiological mechanisms are not yet clarified. Another contributing factor is the lack of efficient systems to sustain drug release at therapeutic concentrations and enhance the survival and function of grafted cells in transplantation procedures. For medical applications the use of biomaterials of different compositions and formats has experienced a boom in the last decades. Although the greater complexity of central nervous system has probably conditioned their extensive use with respect to other organs, the number of biomaterials-based applications to treat the injured brain or in the process of being damaged has grown exponentially. Hydrogel-based biomaterials have constituted a turning point in the treatment of cerebral disorders using a new form of advanced therapy. Hydrogels show mechanical properties in the range of cerebral tissue resulting very suitable for local implantation of drugs and cells. It is also possible to fabricate three-dimensional hydrogel constructs with adaptable mesh size to facilitate axonal guidance and elongation. Along this article, we review the current trends in this area highlighting the positive impact of hydrogel-based biomaterials over the exhaustive control of drug delivery, cell engraftment and axonal reinnervation in brain pathologies.

Background: Bipedal static posturography is widely used to assess postural control. However, standardized methods and evidence on the influence of footwear on balance in comparison to barefoot stance is sparse. Research questions: Is bipedal static posturography applied in a standardized way with respect to demographics and the experimental set-up (systematic review)? Does habitual footwear influence postural control in comparison to barefoot condition during bipedal static posturography in adult patients and healthy subjects (meta-analysis)? Methods: For this systematic review and meta-analysis, a comprehensive follow-up literature search was conducted from March 2009 until January 2020 according to the PRISMA guidelines. Original, research articles reporting on bipedal, unsupported, static posturography in adults (≥18 years) were included according to inclusion criteria (age, sex, height, weight, duration, repetitions, visual/foot condition, sampling frequency). Studies comparing habitual footwear with barefoot condition during bipedal static posturography were included for the meta-analysis. Center of pressure parameters (sway velocity, range, root mean square, paths lengths) with subjects having eyes closed (EC) or open (EO) were analyzed using random effects models. Results: For this systematic review and meta-analysis, 207 and eight out of 5189 studies with 12'341 and 156 subjects, respectively, were eligible. Most studies (89%) reported barefoot, 5% shod, and 6% barefoot and shod measurements. Less than half of studies (44%) included patients of which the minority (13%) suffered from neurological disease. Sway velocity in the anterior-posterior direction was higher in habitual shoes compared to barefoot with EC (SMD: 1.08; 95% CI: 0.68–1.48; p < 0.01; I2 = 0%), with EO (SMD: 0.68; 95% CI: 0.11–1.26; p = 0.02; I2 = 1%), and in the medio-lateral direction with EC (SMD: 1.30; 95% CI: 0.76–1.85, p < 0.01; I2 = 37%). Significance: Methodical heterogeneity of bipedal static posturography hampers studies’ comparability. Thus, we provide a standardized approach to increase knowledge whether habitual footwear decrease postural control in comparison to barefoot stance., Gait & Posture, 92, ISSN:0966-6362, ISSN:1879-2219

The World Health Organization declared the pandemic situation caused by SARSCoV- 2 (Severe Acute Respiratory Syndrome Coronavirus-2) in March 2020, but the detailed pathophysiological mechanisms of Coronavirus disease 2019 (COVID-19) are not yet completely understood. Therefore, to date, few therapeutic options are available for patients with mildmoderate or serious disease. In addition to systemic and respiratory symptoms, several reports have documented various neurological symptoms and impairments of mental health. The current review aims to provide the available evidence about the effects of SARS-CoV-2 infection on mental health. The present data suggest that SARS-CoV-2 produces a wide range of impairments and disorders of the brain. However, a limited number of studies investigated the neuroinvasive potential of SARS-CoV-2. Although the main features and outcomes of COVID-19 are linked to severe acute respiratory illness, the possible damages on the brain should be considered, too.

Background Flow is a subjective psychological state that people report when they are fully involved in an activity to the point of forgetting time and their surrounding except the activity itself. Being in flow during physical/cognitive rehabilitation may have a considerable impact on functional outcome, especially when patients with neurological diseases engage in exercises using robotics, virtual/augmented reality, or serious games on tablets/computer. When developing new therapy games, measuring flow experience can indicate whether the game motivates one to train. The purpose of this study was to identify and systematically review current literature on flow experience assessed in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson’s disease. Additionally, we critically appraised, compared and summarized the measurement properties of self-reported flow questionnaires used in neurorehabilitation setting. Design A systematic review using PRISMA and COSMIN guidelines. Methods MEDLINE Ovid, EMBASE Ovid, CINAHL EBSCO, SCOPUS were searched. Inclusion criteria were (1) peer-reviewed studies that (2) focused on the investigation of flow experience in (3) patients with neurological diseases (i.e., stroke, traumatic brain injury, multiple sclerosis and/or Parkinson’s disease). A qualitative data synthesis was performed to present the measurement properties of the used flow questionnaires. Results Ten studies out of 911 records met the inclusion criteria. Seven studies measured flow in the context of serious games in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson’s disease. Three studies assessed flow in other activities than gaming (song-writing intervention and activities of daily living). Six different flow questionnaires were used, all of which were originally validated in healthy people. None of the studies presented psychometric data in their respective research population. Conclusion The present review indicates that flow experience is increasingly measured in the physical/cognitive rehabilitation setting in patients with neurological diseases. However, psychometric properties of used flow questionnaires are lacking. For exergame developers working in the field of physical/cognitive rehabilitation in patients with neurological diseases, a valid flow questionnaire can help to further optimize the content of the games so that optimal engagement can occur during the gameplay. Whether flow experiences can ultimately have positive effects on physical/cognitive parameters needs further study.

The endocannabinoid (eCB) signaling system plays an important role in the regulation of the central nervous system (CNS). α/β-Hydrolase domain-containing 6 (ABHD6) is a transmembrane serine hydrolase that can hydrolyze monoacylglycerol (MAG) lipids such as endocannabinoid 2-arachidonic acid glycerol (2-AG); participate in neurotransmission, inflammation, glucose and lipid metabolism, tumorigenesis and other biological processes; and be a potential therapeutic target for various neurological diseases, such as traumatic brain injury (TBI), multiple sclerosis (MS), epilepsy, mental illness and pain. This review summarizes the molecular mechanisms of action and biological functions of ABHD6, particularly its mechanism of action in the pathogenesis of neurological diseases, and provides a theoretical basis for finding new pharmacological intervention targets by targeting ABHD6.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has affected over 200 million people globally (including over 30 million people in the United States), with children comprising 12.9% of reported cases in the United States. In children, COVID-19 infection appears to be associated with mild respiratory symptoms; however, serious neurological complications may occur in conjunction with multisystem inflammatory syndrome. A wide spectrum of neurological diseases have been observed in children with COVID-19 infection including encephalitis, acute necrotizing encephalopathy, acute disseminated encephalomyelitis, cytotoxic lesion of the callosal splenium, posterior reversible encephalopathy syndrome, venous sinus thrombosis, vasculitis and infarction, Guillain-Barre syndrome, transverse myelitis, and myositis. This review describes the characteristic magnetic resonance neuroimaging features of these diseases and their differentiations from other imaging mimics. In addition, we review the possible pathophysiology underlying the association between these diseases and COVID-19-infection. As new SARS-CoV-2 variants emerge and COVID-19 infection continues to spread worldwide, pediatricians, radiologists, and first-line care givers should be aware of possible neurological diseases associated with COVID-19 infection when these reported neuroimaging patterns are observed in children during this pandemic.

Microglia and astrocytes maintain tissue homeostasis in the nervous system. Both microglia and astrocytes have pro-inflammatory phenotype and anti-inflammatory phenotype. Activated microglia and activated astrocytes can contribute to several neurological diseases. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), two groups of non-coding RNAs (ncRNAs), can function as competing endogenous RNAs (ceRNAs) to impair the microRNA (miRNA) inhibition on targeted messenger RNAs (mRNAs). LncRNAs and circRNAs are involved in various neurological disorders. In this review, we summarized that lncRNAs and circRNAs participate in microglia dysfunction, astrocyte dysfunction, neuron damage, and inflammation. Thereby, lncRNAs and circRNAs can positively or negatively regulate neurological diseases, including spinal cord injury (SCI), traumatic brain injury (TBI), ischemia-reperfusion injury (IRI), stroke, neuropathic pain, epilepsy, Parkinson’s disease (PD), multiple sclerosis (MS), and Alzheimer’s disease (AD). Besides, we also found a lncRNA/circRNA-miRNA-mRNA regulatory network in microglia and astrocyte mediated neurological diseases. Through this review, we hope to cast light on the regulatory mechanisms of lncRNAs and circRNAs in microglia and astrocyte mediated neurological diseases and provide new insights for neurological disease treatment.

Acute and post-acute neurological symptoms, signs and diagnoses have been documented in an increasing number of patients infected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19). In this review, we aimed to summarize the current literature addressing neurological events following SARS-CoV-2 infection, discuss limitations in the existing literature and suggest future directions that would strengthen our understanding of the neurological sequelae of COVID-19. The presence of neurological manifestations (symptoms, signs or diagnoses) both at the onset or during SARS-CoV-2 infection is associated with a more severe disease, as demonstrated by a longer hospital stay, higher in-hospital death rate or the continued presence of sequelae at discharge. Although biological mechanisms have been postulated for these findings, evidence-based data are still lacking to clearly define the incidence, range of characteristics and outcomes of these manifestations, particularly in non-hospitalized patients. In addition, data from low- and middle-income countries are scarce, leading to uncertainties in the measure of neurological findings of COVID-19, with reference to geography, ethnicity, socio-cultural settings, and health care arrangements. As a consequence, at present a specific phenotype that would specify a post-COVID (or long-COVID) neurological syndrome has not yet been identified. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10848-4.

Background and purpose\ud Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread.\ud \ud Methods\ud Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation (“dystonia-only”) and one accepting dystonia OR tremor in any body part as disease manifestations (“dystonia OR tremor”). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping.\ud \ud Results\ud Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62–0.70 and 0.62–0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread.\ud \ud Conclusions\ud This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals’ risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.

Background: Patients with Myasthenia Gravis (MG) can be treated acutely with therapeutic plasma exchange (TPE) or intravenous immune globulin (IVIG). To date, there is no definitive understanding of which of the two treatments is more effective and safer. The purpose of this study was to systematically review the literature on the comparative efficacy and safety of TPE to other available treatments for MG.Methods: A systematic literature search for studies published between 1997 and 2017 was performed per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using two database sources, MEDLINE (through the PubMed database) and Cochrane Library.Results: The search strategy resulted in 535 articles whose abstracts were reviewed. Among these, 165 full texts articles were reviewed for eligibility and 101 articles were excluded. Of the 165 articles, 64 articles were included for a systematic literature and 11 articles for a meta-analysis.Conclusions: This systematic literature review and meta-analysis of treatment options showed that there was a higher response rate with TPE than IVIG in acute MG patients and patients undergoing thymectomy. There was no difference in mortality between the two treatment options. Our findings highlight the need for additional randomized clinical trials in these patients with MG.

Background and Purpose: CSF therapy is considered a promising therapeutic approach for stroke. We performed a meta-analysis to explore the safety and efficacy of CSF in published clinical stroke studies.Methods: We searched articles online and manually. Two reviewers selected studies independently, selecting data based on study quality, characteristics of intervention (administration time, observation time, type, dose, and injection approach of CSF), and the baseline characteristics of patients (age, sex, hypertension, diabetes, smoker, and lipids) were extracted. Main prognosis outcomes were measured as all-cause death in severe adverse events (SAE) and recurrent stroke in SAE. Secondary outcomes were measured as CD34+ cell counts in periphery blood at day 5, National Institutes of Health Stroke Scale (NIHSS), and Barthel index (BI), Side effects of CSF were taken as the indicator of safety. STATA13 software was used to perform the meta-analysis.Keywords: Stroke, Colony-stimulating factor, Meta-analysis, therapy, Neurological DiseasesResults: This meta-analysis involved 485 patients from eight studies. Among them, 475 patients from seven studies were gauged SAE (all-cause death), 393 patients from six studies were checked SAE (recurrent stroke); 137 patients from three studies underwent CD34+ measurement, 389 patients from six studies were tested NIHSS and 307 patients from five studies accessed BI. Compared with the control group, both all-causes death (RR= 1.73, 95%CI= (0.61, 4.92), P=0.735, I2=0.0%) and recurrent stroke (RR= 0.43, 95%CI= (0.14, 1.32), P=0.214, I2=33.1%) present no statistical differences, indicating that the application of CSF does not statistically alter the prognosis of patients with stroke. The application of CSF effectively enhanced CD34+ cell counts in periphery blood at day 5 (SMD= 1.23, 95%CI= (0.54, 1.92), P=0.04, I2=69.0%) but did not statistically impact NIHSS (SMD= −0.40, 95%CI= (−0.93, 0.13), P ≤ 0.001, I2=79.7%) or BI (SMD= 0.04, 95%CI= (−0.38, 0.46), P=0.068, I2=54.3%).Conclusion: Our study consolidates the security of CSF administration for its exerting no effect on detrimental outcomes. It has proven to be effective in elevating CD34+ cell counts in periphery blood at day 5, indicating CSF may participate in stroke recovery, but its efficacy in stroke recovery remains detected.

Millennium Initiative ICN09_015 Barnard College start-up funds United States Department of Health & Human Services National Institutes of Health (NIH) - USA NINDS R01 NS118012 National Institute of Food and Agriculture, U.S. Department of Agriculture Hatch Program 1012993 Foundation for Food and Agriculture Research Pollinator Health Fund 549049 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1210586 Ver texto de financiacion

Hydroxytyrosol (HT) is a food-sourced phenolic phytochemical with anti-oxidant and anti-inflammatory properties. Adherence to a Mediterranean diet (MD) based on extra virgin olive oil (EVOO), of which HT is one of the principal components, is beneficial for reducing the incidence of chronic neurodegenerative diseases and improving cognitive ability. Accumulating evidence indicates that HT exhibits neuroprotective effects on multiple neurological disorders and neuropathophysiological conditions. Therefore, this paper reviews researches of HT related to nervous system in vitro and in vivo and mechanisms of action, in order to provide the latest views on the beneficial properties of HT in preventing or resisting neurological disorders including chronic neurodegenerative diseases and other neurological diseases, and neuropathophysiological conditions comprising neuroinflammation and neuroregeneration, etc.

Multiple sclerosis (MS) is a central nervous system disease with complex pathogenesis, including two main processes: immune-mediated inflammatory demyelination and progressive degeneration with axonal loss. Despite recent progress in our understanding and management of MS, availability of sensitive and specific biomarkers for these both processes, as well as neuroprotective therapeutic options targeted at progressive phase of disease, are still being sought. Given their abundance in the myelin sheath, lipids are believed to play a central role in underlying immunopathogenesis in MS and seem to be a promising subject of investigation in this field. On the basis of our previous research and a review of the literature, we discuss the current understanding of lipid-related mechanisms involved in active relapse, remission, and progression of MS. These insights highlight potential usefulness of lipid markers in prediction or monitoring the course of MS, particularly in its progressive stage, still insufficiently addressed. Furthermore, they raise hope for new, effective, and stage-specific treatment options, involving lipids as targets or carriers of therapeutic agents.

Objectives: To understand treatment patterns, healthcare resource utilization, and costs of care among patients with spinal muscular atrophy (SMA). Methods: SMA patients were identified from a large managed care population using administrative claims data from January 2006 to March 2016. Patients were classified into infantile, childhood-onset, and late-onset groups based on age of first SMA diagnosis. They were matched 1:1 to non-SMA patients based on age, gender, geography, and health plan type. Results: In the infantile group, 17.4% and 26.1% were treated with invasive and non-invasive ventilation, respectively. Uses of orthotics/orthoses and orthopedic surgery were frequent: 54.5% and 22.7% childhood group; 27.0% and 38.5% late-onset group. Mean per member per month costs in SMA vs. matched non-SMA patients was $25,517 vs. $406 (infantile); $6,357 vs. $188 (childhood-onset); $2,499 vs. $742 (late-onset). Conclusions: SMA patients, particularly with infantile onset, incurred significantly higher healthcare utilization and costs than the general population.

Neurological cases in Nepal are not reported much. Neurological diseases are associated to poor health outcomes including mortality, disability and hospitalization. Epidemiology and clinical pattern of neurological disorders in developing countries remain largely unknown. This is a descriptive study to understand the burden of disease faced by neurologists and internists in a hospital of Nepal. This is a retrospective study of medical records of patients admitted in the Neurology unit of medical ward of Dhulikhel Hospital. A total of 318 patients were admitted during the period of July 2014to January 2015. Diagnosis was established by clinical, radiological, nerve conduction studies, electroencephalography and cerebrospinal fl uidanalysis. A total of 318 patients records during the above mentioned period were reviewed. Common neurological diseases identified were vascular: 138(43.40%); seizure: 60(18.87%); infectious: 20(6.29%); demyelinating: 12(3.77%); degenerative: 14(4.40%); peripheral neuropathy:14(4.40%); and others (mass lesion, ataxia, myelopathy) 60(18.87%). Cerebrovasculardisease is the most common cause of admission of patients in the neurological unit of the hospital. There are differences in the neurological diseases with respect to age, gender and ethnicity.

Astrocytes, a class of morphologically and functionally diverse primary homeostatic neuroglia, are key keepers of neural tissue homeostasis and fundamental contributors to brain defence in pathological contexts. Failure of astroglial support and defence facilitate the evolution of neurological diseases, which often results in aberrant synaptic transmission, neurodegeneration and death of neurones. In Alzheimer’s disease (AD), astrocytes undergo complex and multifaceted metamorphoses ranging from atrophy with loss of function to reactive astrogliosis with hypertrophy. Astroglial asthenia underlies reduced homeostatic support and neuroprotection that may account for impaired synaptic transmission and neuronal demise. Reactive astrogliosis which mainly develops in astrocytes associated with senile plaque is prominent at the early to moderate stages of AD manifested by mild cognitive impairment; downregulation of astrogliosis (reflecting astroglial paralysis) is associated with late stages of the disease characterised by severe dementia. Cell-specific therapies aimed at boosting astroglial supportive and defensive capabilities and preventing astroglial paralysis may offer new directions in preventing, arresting, or even curing AD-linked neurodegeneration.

Dramatic breakthroughs in the treatment and assessment of neurological diseases are lacking. We believe that conventional methods have several limitations. Computerized technologies, including virtual reality, augmented reality, and robot assistant systems, are advancing at a rapid pace. In this study, we used Parkinson's disease (PD) as an example to elucidate how the latest computerized technologies can improve the diagnosis and treatment of neurological diseases. Dopaminergic medication and deep brain stimulation remain the most effective interventions for treating PD. Subjective scales, such as the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr stage, are still the most widely used assessments. Wearable sensors, virtual reality, augmented reality, and robot assistant systems are increasingly being used for evaluation of patients with PD. The use of such computerized technologies can result in safe, objective, real-time behavioral assessments. Our experiences and understanding of PD have led us to believe that such technologies can provide real-time assessment, which will revolutionize the traditional assessment and treatment of PD. New technologies are desired that can revolutionize PD treatment and facilitate real-time adjustment of treatment based on motor fluctuations, such as telediagnosis systems and "smart treatment systems." The use of these technologies will substantially improve both the assessment and the treatment of neurological diseases before next-generation treatments, such as stem cell and genetic therapy, and next-generation assessments, can be clinically practiced, although the current level of artificial intelligence cannot replace the role of clinicians.

Resveratrol, a phytoalexin with a wide range of pharmacological properties is synthesised by plants in response to stress, injury, infection or UV radiations. As it is a secondary metabolite with many health promoting properties, various methods employing microorganisms and genetic manipulation of different synthetic enzymes, have been comprehensively studied to increase its production. Its rapid metabolism and low bioavailability have been addressed by the use of bio enhancers and nano-formulations. This flavonoid is extensively researched due to its pharmacological properties such as anti-oxidative, anti-inflammatory and immuno-modulating effects. Knowledge of these properties of resveratrol has led to elaborate studies on its effect on diabetes, neurodegenerative diseases, cancer, ageing, obesity and cardiovascular diseases. At molecular level it targets sirtuin, adenosine monophosphate kinase, nuclear Factor-κB, inflammatory cytokines, anti-oxidant enzymes along with cellular processes such as angiogenesis, apoptosis, mitochondrial biogenesis, gluconeogenesis and lipid metabolism. This review discusses the properties of resveratrol and the different approaches of addressing the unfavourable synthesis and pharmacokinetics of this stilbene. Pre-clinical evaluations of resveratrol on diabetes mellitus, cardiovascular and neurological diseases are elaborately discussed and the underlying pathways involved in its therapeutic activity have been given paramount importance. Following the pre-clinical studies, clinical trials on the same reveal the efficacy of resveratrol in the effective management of these diseases. This review provides an intricate insight on resveratrol's significance from a dietary component to a therapeutic agent.

Introduction: The field of brain–machine interfaces (BMI) for upper limb (UL) orthoses is growing exponentially due to improvements in motor performance, quality of life, and functionality of people with neurological diseases. Considering this, we planned a systematic review to investigate the effects of BMI-controlled UL orthoses for rehabilitation of patients with neurological disorders.Methods: This systematic review and meta-analysis protocol was elaborated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P 2015) and Cochrane Handbook for Systematic Reviews of Interventions. A search will be conducted on Pubmed, IEEE Xplore Digital Library, Medline, and Web of Science databases without language and year restrictions, and Patents Scope, Patentlens, and Google Patents websites in English, Spanish, French, German, and Portuguese between 2011 and 2021. Two independent reviewers will include randomized controlled trials and quasi-experimental studies using BMI-controlled active UL orthoses to improve human movement. Studies must contain participants aged >18 years, diagnosed with neurological disorders, and with impaired UL movement. Three independent reviewers will conduct the same procedure for patents. Evidence quality and risk of bias will be evaluated following the Cochrane collaboration by two review authors. Meta-analysis will be conducted in case of homogeneity between groups. Otherwise, a narrative synthesis will be performed. Data will be inserted into a table containing physical description, UL orthoses control system, and effect of BMI-controlled orthoses.Discussion: BMI-controlled orthoses can assist individuals in several routine activities and provide functional independence and sense of overcoming limitations imposed by the underlying disease. These benefits will also be associated with orthoses descriptions, safety, portability, adverse events, and tools used to assess UL motor performance in patients with neurological disorders.PROSPERO Registration Number: CRD42020182195.

Background Parkinson disease (PD) is a neurodegenerative disorder associated with a broad spectrum of motor and nonmotor symptoms. Any proposed cure needs to address the many aspects of the disease. Stem cell therapy may have potential in this regard as indicated in recent preclinical and clinical studies. Objective This protocol aims to examine the safety and therapeutic benefit of human Wharton jelly-derived mesenchymal stem cells (WJ-MScs) and their derivatives, neuronal stem cells (NSCs) in PD. Methods This clinical trial is a double-arm, single-blinded, phase I-II interventional study. Participants have been allocated to 1 of 2 groups: one receiving allogeneic WJ-MSCs alone, the other receiving NSCs and WJ-MScs. Participants are being followed-up and assessed over a period of 6 months. To assess safety, an incidence of treatment-emergent adverse events (TEAEs) tool tailored for PD is being used immediately and up to 6 months after treatment. For efficacy assessment, a number of factors are being used, including the gold standard severity test and the Unified Parkinson Disease Rating Scale. In addition, the following standardized assessments for different common symptoms in PD are being included: motor (both subjectively and objectively assessed with wearable sensors), sensory, quality of life and psychological well-being, cognition, and sleep quality. Furthermore, immune-modulatory cytokines and neuronal damage versus regeneration markers in PD, including the neuronal protein linked to PD, α-synuclein, are being monitored. Results Ten patients have been enrolled in this study and thus participant recruitment has been completed. The study status is active and beyond the recruiting stage. Study chart implementation, data collection, and analysis are ongoing. Conclusions The combination of NSCs and MSCs in PD may be useful for harnessing the best of the immunomodulation and neural repair characteristics of these cell types. The tailored comprehensive and scaled TEAEs and the variety of evaluation tools used enables a comprehensive assessment of this cellular therapy treatment protocol. A consideration of this expanded tool set is important in the design of future clinical studies for PD. Trial Registration ClinicalTrials.gov NCT03684122; https://clinicaltrials.gov/ct2/show/NCT03684122 International Registered Report Identifier (IRRID) DERR1-10.2196/29695

Neurological disorders are diseases of the central and peripheral nervous system that affect millions of people, and the numbers are rising gradually. In the pathogenesis of neurodegenerative diseases, the roles of many signaling pathways were elucidated; however, the exact pathophysiology of neurological disorders and possible effective therapeutics have not yet been precisely identified. This necessitates developing multi-target treatments, which would simultaneously modulate neuroinflammation, apoptosis, and oxidative stress. The present review aims to explore the potential therapeutic use of astaxanthin (ASX) in neurological and neuroinflammatory diseases. ASX, a member of the xanthophyll group, was found to be a promising therapeutic anti-inflammatory agent for many neurological disorders, including cerebral ischemia, Parkinson’s disease, Alzheimer’s disease, autism, and neuropathic pain. An effective drug delivery system of ASX should be developed and further tested by appropriate clinical trials. Deanship of Scientific Research at Princess Nourah bint Abdulrahman University

As the organ with the highest demand for oxygen, the brain has a poor tolerance to ischemia and hypoxia. Despite severe ischemia/hypoxia induces the occurrence and development of various central nervous system (CNS) diseases, sublethal insult may induce strong protection against subsequent fatal injuries by improving tolerance. Searching for potential measures to improve brain ischemic/hypoxic is of great significance for treatment of ischemia/hypoxia related CNS diseases. Ischemic/hypoxic preconditioning (I/HPC) refers to the approach to give the body a short period of mild ischemic/hypoxic stimulus which can significantly improve the body's tolerance to subsequent more severe ischemia/hypoxia event. It has been extensively studied and been considered as an effective therapeutic strategy in CNS diseases. Its protective mechanisms involved multiple processes, such as activation of hypoxia signaling pathways, anti‐inflammation, antioxidant stress, and autophagy induction, etc. As a strategy to induce endogenous neuroprotection, I/HPC has attracted extensive attention and become one of the research frontiers and hotspots in the field of neurotherapy. In this review, we discuss the basic and clinical research progress of I/HPC on CNS diseases, and summarize its mechanisms. Furthermore, we highlight the limitations and challenges of their translation from basic research to clinical application., IPC/HPC/RIPC exert neurprotective effects by several molecular mechanisms, including activating HIF‐1α signaling, reducing ROS, activating autophagy, anti‐apoptosis, anti‐inflammation, reducing excitotoxicity, and enhancing BBB integrity. BBB, blood brain barrier; HIF, hypoxia inducible factor; HPC, hypoxic preconditioning; IPC, ischemic preconditioning; RIPC, remote ischemic preconditioning; ROS, reactive oxygen species.

RNA-based therapeutics have emerged as one of the most powerful therapeutic options used for the modulation of gene/protein expression and gene editing with the potential to treat neurodegenerative diseases. However, the delivery of nucleic acids to the central nervous system (CNS), in particular by the systemic route, remains a major hurdle. This review will focus on the strategies for systemic delivery of therapeutic nucleic acids designed to overcome these barriers. Pathways and mechanisms of transport across the blood-brain barrier which could be exploited for delivery are described, focusing in particular on smaller nucleic acids including antisense oligonucleotides (ASOs) and small interfering RNA (siRNA). Approaches used to enhance delivery including chemical modifications, nanocarrier systems, and target selection (cell-specific delivery) are critically analyzed. Learnings achieved from a comparison of the successes and failures reported for CNS delivery of ASOs versus siRNA will help identify opportunities for a wider range of nucleic acids and accelerate the clinical translation of these innovative therapies.

International audience; Coenzyme Q (CoQ) is a ubiquitous lipid serving essential cellular functions. It is the only component of the mitochondrial respiratory chain that can be exogenously absorbed. Here, we provide an overview of current knowledge, controversies, and open questions about CoQ intracellular and tissue distribution, in particular in brain and skeletal muscle. We discuss human neurological diseases and mouse models associated with secondary CoQ deficiency in these tissues and highlight pharmacokinetic and anatomical challenges in exogenous CoQ biodistribution, recent improvements in CoQ formulations and imaging, as well as alternative therapeutical strategies to CoQ supplementation. The last section proposes possible mechanisms underlying secondary CoQ deficiency in human diseases with emphasis on neurological and neuromuscular disorders.

Neurological disorders such as Alzheimer's disease, stroke, and brain cancers are difficult to treat with current drugs as their delivery efficacy to the brain is severely hampered by the presence of the blood–brain barrier (BBB). Drug delivery systems have been extensively explored in recent decades aiming to circumvent this barrier. In particular, polymeric nanoparticles have shown enormous potentials owing to their unique properties, such as high tunability, ease of synthesis, and control over drug release profile. However, careful analysis of their performance in effective drug transport across the BBB should be performed using clinically relevant testing models. In this review, polymeric nanoparticle systems for drug delivery to the central nervous system are discussed with an emphasis on the effects of particle size, shape, and surface modifications on BBB penetration. Moreover, the authors critically analyze the current in vitro and in vivo models used to evaluate BBB penetration efficacy, including the latest developments in the BBB‐on‐a‐chip models. Finally, the challenges and future perspectives for the development of polymeric nanoparticles to combat neurological disorders are discussed., This review highlights the development of polymeric nanoparticles for drug delivery to the central nervous system. The synthesis of promising polymeric nanoparticles is discussed with an emphasis on the effects of particle size, shape, and surface modification on blood–brain barrier (BBB) transfer. Moreover, current in vitro and in vivo models are discussed, including the latest advances in BBB‐on‐a‐chip models.

Introduction and purpose: The SARS-CoV-2 virus is able to cause abnormalities in the functioning of the nervous system and induce neurological symptoms with the features of encephalopathy, disturbances of consciousness and concentration and a reduced ability to sense taste and smell as well as headaches. One of the methods of detecting these types of changes in COVID-19 patients is an electroencephalogram (EEG) test, which allows information to be obtained about the functioning of the brain as well as diagnosing diseases and predicting their consequences. The aim of the study was to review the latest research on changes in EEG in patients with COVID-19 as a basis for further quantitative electroencephalogram (QEEG) diagnostics and EEG neurofeedback training. Description of the state of knowledge: Based on the available scientific literature using the PubMed database from 2020 and early 2021 regarding changes in the EEG records in patients with COVID-19, 17 publications were included in the analysis. In patients who underwent an EEG test, changes in the frontal area were observed. A few patients were not found to be responsive to external stimuli. Additionally, a previously non-emerging, uncommon pattern in the form of continuous, slightly asymmetric, monomorphic, biphasic and slow delta waves occurred. Conclusion: The results of this analysis clearly indicate that the SARS-CoV-2 virus causes changes in the nervous system that can be manifested and detected in the EEG record. The small number of available articles, the small number of research groups and the lack of control groups suggest the need for further research regarding the short and long term neurological effects of the SARS-CoV-2 virus and the need for unquestionable confirmation that observed changes were caused by the virus per se and did not occur before. The presented studies described non-specific patterns appearing in encephalograms in patients with COVID-19. These observations are the basis for more accurate QEEG diagnostics and EEG neurofeedback training.

Johann Ludwig Wilhelm Thudicum described sphingolipids (SLs) in the late nineteenth century, but it was only in the past fifty years that SL research surged in importance and applicability. Currently, sphingolipids and their metabolism are hotly debated topics in various biochemical fields. Similar to other macromolecular reactions, SL metabolism has important implications in health and disease in most cells. A plethora of SL-related genetic ailments has been described. Defects in SL catabolism can cause the accumulation of SLs, leading to many types of lysosomal storage diseases (LSDs) collectively called sphingolipidoses. These diseases mainly impact the neuronal and immune systems, but other systems can be affected as well. This review aims to present a comprehensive, up-to-date picture of the rapidly growing field of sphingolipid LSDs, their etiology, pathology, and potential therapeutic strategies. We first describe LSDs biochemically and briefly discuss their catabolism, followed by general aspects of the major diseases such as Gaucher, Krabbe, Fabry, and Farber among others. We conclude with an overview of the available and potential future therapies for many of the diseases. We strive to present the most important and recent findings from basic research and clinical applications, and to provide a valuable source for understanding these disorders.

Background: Infantile spasms is a rare disease characterized by distinct seizures and hypsarrhythmia. Adrenocorticotropic hormone (ACTH) is available as a natural product (repository corticotropin injection, [RCI]; Acthar® Gel) and as synthetic analogs. RCI is a naturally-sourced complex mixture of purified ACTH analogs and other pituitary peptides approved by the United States Food and Drug Administration as a monotherapy for the treatment of infantile spasms. RCI is commonly used in the United States. Outside the United States, synthetic analogs of ACTH—synthetic ACTH1-24 (tetracosactide) and synthetic ACTH1-39 (corticotropin carboxymethyl-cellulose [CCMC])—are used. The efficacy of RCI may differ from that of synthetic ACTH treatments based on the structure of peptide; however, no head-to-head clinical trials have compared the efficacy of RCI and synthetic ACTH treatments. Objective: A systematic review and indirect treatment comparison of clinical trials was conducted to assess the comparative efficacy of RCI and synthetic ACTH treatments in infantile spasms. Methods: A search was conducted in MEDLINE, EMBASE, and Cochrane databases through September 30, 2020. Relevant clinical trials on RCI or synthetic ACTH therapy and reporting either cessation of spasms or resolution of hypsarrhythmia, separately or as a combined outcome were included. A Bayesian indirect treatment comparison using a fixed-effects model was used for comparative efficacy. Results: Of 473 citations screened, 21 studies were reviewed qualitatively. In the indirect treatment comparison of six eligible clinical trial studies, the odds of achieving efficacy outcomes were five to eight times greater with RCI than with tetracosactide and 14 to 16 times greater than CCMC. This translated to a risk reduction of 10% to 14% and 40% to 50% with RCI versus tetracosactide and CCMC, respectively. For every two to five patients treated, RCI improved efficacy outcomes in one additional patient compared to synthetic ACTH (adjusted number needed-to-treat). Conclusions: Based on the available limited evidence, results suggest RCI may be more efficacious for infantile spasms than synthetic ACTH treatments. Our findings provide a blueprint to inform the design of future prospective studies for the treatment of infantile spasms., A systematic review and indirect treatment comparison of clinical trials was conducted to assess the comparative efficacy of RCI and synthetic ACTH treatments in infantile spasms.

Background It has been well established that the TMEM106B gene rs1990622 variant was a frontotemporal dementia (FTD) risk factor. Until recently, growing evidence highlights the role of TMEM106B in Alzheimer’s disease (AD). However, it remains largely unclear about the role of rs1990622 variant in AD. Methods Here, we conducted comprehensive analyses including genetic association study, gene expression analysis, eQTLs analysis, and colocalization analysis. In stage 1, we conducted a genetic association analysis of rs1990622 using large-scale genome-wide association study (GWAS) datasets from International Genomics of Alzheimer’s Project (21,982 AD and 41,944 cognitively normal controls) and UK Biobank (314,278 participants). In stage 2, we performed a gene expression analysis of TMEM106B in 49 different human tissues using the gene expression data in GTEx. In stage 3, we performed an expression quantitative trait loci (eQTLs) analysis using multiple datasets from UKBEC, GTEx, and Mayo RNAseq Study. In stage 4, we performed a colocalization analysis to provide evidence of the AD GWAS and eQTLs pair influencing both AD and the TMEM106B expression at a particular region. Results We found (1) rs1990622 variant T allele contributed to AD risk. A sex-specific analysis in UK Biobank further indicated that rs1990622 T allele only contributed to increased AD risk in females, but not in males; (2) TMEM106B showed different expression in different human brain tissues especially high expression in cerebellum; (3) rs1990622 variant could regulate the expression of TMEM106B in human brain tissues, which vary considerably in different disease statuses, the mean ages at death, the percents of females, and the different descents of the selected donors; (4) colocalization analysis provided suggestive evidence that the same variant contributed to AD risk and TMEM106B expression in cerebellum. Conclusion Our comprehensive analyses highlighted the role of FTD rs1990622 variant in AD risk. This cross-disease approach may delineate disease-specific and common features, which will be important for both diagnostic and therapeutic development purposes. Meanwhile, these findings highlight the importance to better understand TMEM106B function and dysfunction in the context of normal aging and neurodegenerative diseases.

Ketogenic diet (KD) is based on restriction of carbohydrate intake. Metabolism is forced to obtain energy starting from β-oxidation of fatty acids which, turned into ketone bodies, can also be used by central nervous system (CNS). KD use in treatment of chronic migraine has recently been considered. We set out to verify modification of symptoms in patients with refractory chronic migraine in response to KD. Fifty patients were enrolled of which 38 completed the procedures the study and 23 were considered in the statistics. All of the patients considered in our study were affected by medication overuse headache (MOH). They were on a KD for 3 months. The following parameters have been checked at t = 0 and every 30 days for 6 months: migraine episode length (n. hours/day), frequency (n. days/month), level of pain of every episode measured on a scale from 1 to 3 (1 = mild; 2 = moderate; 3 = severe), and n. analgesic drugs taken/month. Days with symptoms decreased from 30 (median value) to 7.5 with p

Insomnia is defined as difficulties of initiating and maintaining sleep, early awakening and poor subjective sleep quality despite adequate opportunity and circumstances for sleep with impairment of daytime performance. These components of insomnia – namely persistent sleep difficulties despite of adequate sleep opportunity resulting in daytime dysfunction - appear secondary or co-morbid to neurological diseases. Comorbid insomnia originates from neurodegenerative, inflammatory, traumatic or ischemic changes in sleep regulating brainstem and hypothalamic nuclei with consecutive changes of neurotransmitters. Symptoms of neurological disorders (i.e motor deficits), co-morbidities (i.e. pain, depression, anxiety) and some disease-specific pharmaceuticals may cause insomnia and/or other sleep problems.This guideline focuses on insomnias in headaches, neurodegenerative movement disorders, multiple sclerosis, traumatic brain injury, epilepsies, stroke, neuromuscular disease and dementia.The most important new recommendations are: Cognitive behavioral therapy (CBTi) is recommended to treat acute and chronic insomnia in headache patients. Insomnia is one of the most frequent sleep complaints in neurodegenerative movement disorders. Patients may benefit from CBTi, antidepressants (trazodone, doxepin), melatonin and gaba-agonists. Insomnia is a frequent precursor of MS symptoms by up to 10 years. CBTi is recommended in patients with MS, traumatic brain injury and. Melatonin may improve insomnia symptoms in children with epilepsies. Patients with insomnia after stroke can be treated with benzodiazepine receptor agonists and sedating antidepressants. For patients with dementia suffering from insomnia trazodone, light therapy and physical exercise are recommended.

Background: Coronavirus disease 2019 (COVID-19) pandemic and lockdown period may induce an impairment in quality of life (QoL), disruption in treatment (DIT), and posttraumatic stress disorder (PTSD) in chronic neurological diseases (CNDs). To reach this information, a multicenter, cross-sectional study (COVQoL-CND) was planned. Parkinson’s disease (PD), headache (HA), multiple sclerosis (MS), epilepsy (EP), polyneuropathy (PNP), and cerebrovascular disease (CVD) were selected as the CND. Methods: The COVQoL-CND study includes demographic data, the World Health Organization Quality of Life short form (WHOQOL-BREF), and Impact of Event Scale-Revised (IES-R) forms. Results: The mean age of a total of 577 patients was 49 ± 17 (19–87 years), and the ratio of female/male was 352/225. The mean age of patients with PD, HA, MS, EP, PNP, and CVD were 65 ± 11, 39 ± 12, 38 ± 10, 47 ± 17, 61 ± 12, and 60 ± 15 years, respectively. The IES-R scores were found to be higher in the younger group, those with comorbid disease, contacted with CO­VID-19 patients, or diagnosed with COVID-19. In the group with a high IES-R score, the rate of DIT was found to be high. IES-R scores were negatively correlated with QoL. IES-R total scores were found highest in the CVD group and lowest in the PD group. The ratio of DIT was found highest in the PNP group and the lowest in the EP group. Contact with CO­VID-19 patients was high in the EP and HA group. Conclusions: The results of the COVQoL-CND study showed that lockdown causes posttraumatic stress and deterioration in the QoL in CND.