Evaluation of power wheelchair driving performance in simulator compared to driving in real-life situations: the SIMADAPT (simulator ADAPT) project-a pilot study.

OBJECTIVE: The objective of this study was to evaluate users' driving performances with a Power Wheelchair (PWC) driving simulator in comparison to the same driving task in real conditions with a standard power wheelchair. METHODS: Three driving circuits of progressive difficulty levels (C1, C2, C3) that were elaborated to assess the driving performances with PWC in indoor situations, were used in this study. These circuits have been modeled in a 3D Virtual Environment to replicate the three driving task scenarios in Virtual Reality (VR). Users were asked to complete the three circuits with respect to two testing conditions during three successive sessions, i.e. in VR and on a real circuit (R). During each session, users completed the two conditions. Driving performances were evaluated using the number of collisions and time to complete the circuit. In addition, driving ability by Wheelchair Skill Test (WST) and mental load were assessed in both conditions. Cybersickness, user satisfaction and sense of presence were measured in VR. The conditions R and VR were randomized. RESULTS: Thirty-one participants with neurological disorders and expert wheelchair drivers were included in the study. The driving performances between VR and R conditions were statistically different for the C3 circuit but were not statistically different for the two easiest circuits C1 and C2. The results of the WST was not statistically different in C1, C2 and C3. The mental load was higher in VR than in R condition. The general sense of presence was reported as acceptable (mean value of 4.6 out of 6) for all the participants, and the cybersickness was reported as acceptable (SSQ mean value of 4.25 on the three circuits in VR condition). CONCLUSION: Driving performances were statistically different in the most complicated circuit C3 with an increased number of collisions in VR, but were not statistically different for the two easiest circuits C1 and C2 in R and VR conditions. In addition, there were no significant adverse effects such as cybersickness. The results show the value of the simulator for driving training applications. Still, the mental load was higher in VR than in R condition, thus mitigating the potential for use with people with cognitive disorders. Further studies should be conducted to assess the quality of skill transfer for novice drivers from the simulator to the real world. Trial registration Ethical approval n ∘ 2019-A001306-51 from Comité de Protection des Personnes Sud Mediterranée IV. Trial registered the 19/11/2019 on ClinicalTrials.gov in ID: NCT04171973.

Evidence-Based Mind-Body Interventions for Children and Adolescents with Functional Neurological Disorder.

LEARNING OBJECTIVES: • Develop and implement treatment plans for children and adolescents with functional neurological disorder (FND)• Outline a plan to increase awareness and standardize the care for patients with FND using evidence-based interventions. ABSTRACT: Functional neurological disorder (FND) in children and adolescents involves the biological embedding of lived experience in the body and brain. This embedding culminates in stress-system activation or dysregulation and in aberrant changes in neural network function. In pediatric neurology clinics, FND represents up to one-fifth of patients. Current research shows good outcomes with prompt diagnosis and treatment using a biopsychosocial, stepped-care approach. At present, however-and worldwide-FND services are scarce, the result of long-standing stigma and ingrained belief that patients with FND do not suffer from a real ("organic") disorder and that they therefore do not require, or even deserve, treatment. Since 1994, the Mind-Body Program for children and adolescents with FND at The Children's Hospital at Westmead in Sydney, Australia-run by a consultation-liaison team-has delivered inpatient care to hundreds of patients with FND and outpatient care to hundreds of others. For less-disabled patients, the program enables community-based clinicians to implement biopsychosocial interventions locally by providing a positive diagnosis (by a neurologist or pediatrician), a biopsychosocial assessment and formulation (by clinicians from the consultation-liaison team), a physical therapy assessment, and clinical support (from the consultation-liaison team and the physiotherapist). In this Perspective we describe the elements of a biopsychosocial mind-body program intervention capable of providing, as needed, effective treatment to children and adolescents with FND. Our aim is to communicate to clinicians and institutions around the world what is needed to establish effective community treatment programs, as well as hospital inpatient and outpatient interventions, in their own health care settings.

The clinical management of functional neurological disorder: A scoping review of the literature.

OBJECTIVE: To date, there have been no reviews bringing together evidence on the clinical management of functional neurological disorder (FND) and patients', caregivers', and healthcare workers' experiences. This review provides an overview of the literature focused on the clinical management of FND. METHODS: Four databases were searched, and a consultation exercise was conducted to retrieve relevant records dated from September 2010 to September 2020. Articles documenting diagnostic methods, treatments or interventions, or the experiences and perspectives of patients and healthcare workers in the clinical management of FND were included. RESULTS: In total, 2756 records were retrieved, with 162 included in this review. The diagnostic methods reported predominantly included positive clinical signs, v-EEG and EEG. Psychological treatments and medication were the most reported treatments. Mixed findings of the effectiveness of CBT were found. Haloperidol, physiotherapy and scripted diagnosis were found to be effective in reducing FND symptoms. Several facilitators and barriers for patients accessing treatment for FND were reported. CONCLUSION: The literature describing the clinical management for FND has increased considerably in recent times. A wide variety of diagnostic tools and treatments and interventions were found, with more focus being placed on tests that confirm a diagnosis than 'rule-out' tests. The main treatment type found in this review was medication. This review revealed that there is a lack of high-quality evidence and reflects the need for official clinical guidelines for FND, providing healthcare workers and patients the support needed to navigate the process to diagnose and manage FND.

Personality traits related to cognitive functioning in patients with functional neurological disorder.

Cognitive symptoms are prevalent in patients with functional neurological disorder (FND). Several studies have suggested that personality traits such as neuroticism may play a pivotal role in the development of FND. FND has also been associated with alexithymia: patients with FND report difficulties in identifying, analyzing, and verbalizing emotions. Whether or not alexithymia and other personality traits are associated with cognitive symptomatology in patients with FND is unknown. In the current study, we explored whether the Big Five personality model factors (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and alexithymia were associated with cognitive functioning in FND. Twenty-three patients with FND were assessed using a neuropsychological assessment and questionnaire assessment to explore personality traits (Neuroticism-Extraversion-Openness Five-Factor Inventory) and alexithymia (Bermond-Vorst Alexithymia Questionnaire). The results indicated that high conscientiousness was associated with lower planning scores (ρ = -0.52, p = .012) and high scores on alexithymia were associated with lower scores on verbal memory scores (ρ = -0.46, p = .032) and lower sustained attention scores (ρ = -0.45, p = .046). The results did not remain significant after controlling for multiple testing. The preliminary results of our study suggest that personality and cognitive symptomatology in patients with FND are topics that should be further explored in future studies, as cognitive symptomology can affect treatment results.

Brain borders at the central stage of neuroimmunology.

The concept of immune privilege suggests that the central nervous system is isolated from the immune system. However, recent studies have highlighted the borders of the central nervous system as central sites of neuro-immune interactions. Although the nervous and immune systems both function to maintain homeostasis, under rare circumstances, they can develop pathological interactions that lead to neurological or psychiatric diseases. Here we discuss recent findings that dissect the key anatomical, cellular and molecular mechanisms that enable neuro-immune responses at the borders of the brain and spinal cord and the implications of these interactions for diseases of the central nervous system.

Data on medication adherence in adults with neurological disorders: The NeuroGerAd study.

Nonadherence to medication is a common issue that goes along with increased morbidity and mortality and immense health care costs. To improve medication adherence and outcome in ill people, their reasons of not taking their prescribed medication must be known. Here a dataset is presented based on the longitudinal observational NeuroGerAd study in adults with neurological disorders (N = 910). The dataset contains demographic background variables as well as measures of adherence, medication changes after hospital discharge, comprehensive geriatric assessments, personality, patient-physician relationship, and health-related quality of life. As such, the dataset offers unique opportunities to enable a plethora of analyses on personal, social, and institutional factors influencing medication adherence.

Treatment of Pediatric Functional Neurological Symptom Disorder: A Review of the State of the Literature.

Functional Neurological Symptom Disorder (FNSD), or experiencing neurological symptoms incompatible with either a neurological condition or a medical condition, is a common condition presenting in children and adolescents. It is associated with impairment in quality of life for patients and their families and represents a significant burden to the healthcare system. There is currently limited research available regarding effective treatment of pediatric FNSD. Currently, only one RCT exists studying effective treatment of FNSD in children and adolescents, and it is limited to one sub-type of FNSD and only examined cognitive behavioral therapy compared to supportive therapy. Despite this, almost all published research supports good prognosis for pediatric FNSD with all studies reporting improvement either in FNSD symptoms or in the quality of life and functioning of patients with FNSD. The most support was found for the use of cognitive behavioral therapy either as a stand-alone treatment or in the context of interdisciplinary treatment. Future research should focus on increasing the rigor of research, including expanding RCTs to include additional sub-types of FNSD and comparing across various treatment modalities.

Candesartan protects against d-galactose induced - Neurotoxicity and memory deficit via modulation of autophagy and oxidative stress.

PURPOSE: d-galactose induces neuroinflammation and memory deficit via oxidative stress. Candesartan is an angiotensin II-receptor blocker and has proved neuroprotective properties. This study aimed to investigate the neuroprotective effect of candesartan against d-galactose induced neuroinflammation and memory deficit via autophagy. METHODS: Twenty-eight male Wistar rats aged 3 months were divided into four equal groups: control (vehicle), d-gal (100 mg/kg d-galactose), cand (1 mg/kg candesartan), and cand+d-gal (100 mg/kg d-galactose & 1 mg/kg candesartan). All treatments were given orally and daily for 4 weeks. Assessment of memory was done using Morris water maze (MWM) test. Brain tissue was assessed for malondialdehyde (MDA), total thiol, catalase activity, glial fibrillary acidic protein (GFAP) and gene expression of TNF-α, GDNF-1 as well as autophagy genes (Beclin 1 and ATG 5). RESULTS: Prophylactic treatment of candesartan in d-galactose-treated rats significantly (p < 0.001) reduced oxidative stress via reduction of MDA as well as elevation of catalase activity and total thiol levels. Additionally, candesartan prophylactic treatment significantly increased gene expression of GDNF-1 and decreased gene expression of TNF-α. Furthermore, candesartan significantly increased the expression of autophagy related gene (Beclin 1 and ATG 5) in cand+d-gal treated rats. These results were supported by the histopathological findings which showed that candesartan prevented the neuronal injury in the cerebral cortex and hippocampus and decreased GFAP positive cells of the d-galactose-treated rats. Moreover, MWM test showed that candesartan significantly improved memory deficit in cand+d-gal treated rats. CONCLUSION: Candesartan prevents d-galactose-induced neurotoxicity and memory deficit via activating autophagy and decreasing oxidative stress. Therefore, candesartan was a good candidate for age-related neurodegenerative disorders and memory deficit.

Interactions of comorbid neuropsychiatric subsyndromes with neurodegenerative and cerebrovascular pathologies on cognition.

Comorbid neuropsychiatric symptoms are commonly found in individuals with dementia and is likely influenced by a combination of neurodegenerative and cerebrovascular pathophysiology. We evaluated the associations of a validated composite MRI-based quantitative measure of both neurodegeneration (hippocampus volume and cortical thickness of AD-specific regions) and cerebrovascular disease (CeVD; white matter hyperintensities and infarcts) with neuropsychiatric subsyndromes, and their interactions on cognition in a community-based sample across the disease spectrum (N = 773). Lower composite MRI scores corresponding to greater comorbid neurodegeneration and CeVD burden were associated with hyperactivity (OR = 1.48) and apathy (OR = 1.90) subsyndromes. Lower MRI scores with concomitant hyperactivity was associated with greater cognitive impairment, especially in patients who were at least moderately impaired, while the interaction with apathy was not dependent on disease stage. These MRI scores interaction models resulted in a better fit than models consisting of neurodegeneration or CeVD alone. Integrating multiple biomarkers with specific, disease stage-dependent neuropsychiatric subsyndromes may provide a more holistic risk profile to facilitate the identification of individuals at the highest risk of disease progression.

Persons with Co-Existing Neurological Disorders: Risk Analysis, Considerations and Management in COVID-19 Pandemic.

Increasing reports of neurological symptoms in COVID-19 patient's warrant clinicians to adopt and define the standardized diagnostic and managing protocols in order to investigate the linkage of neurological symptoms in COVID-19. Encephalitis, anosmia, acute cerebrovascular disease and ageusia are some of the emerging neurological manifestations which are reported in several cohort studies on hospitalized patients with COVID-19. Although the COVID-19 pandemic is primarily associated with infection of the respiratory tract system, but measures like lockdown and restricted physical movements to control the spread of this infection will certainly have neurobehavioural implications. Additionally, some of the patients with pre-existing neurological manifestations like epilepsy, Parkinson's and Alzheimer's disease are more prone to infection and demand extra care as well as improvised treatment. In this review, we have focused on the neurovirological clinical manifestations associated with the COVID-19 pandemic. Although the prevalence of neurovirological manifestations is rare increasing reports cannot be ignored and needs to be discussed thoroughly with respect to risk analysis and considerations for developing a management strategy. This also helps in defining the burden of neurological disorders associated with COVID-19 patients.

Work and everyday life in a digitalized time: Experiences of people with subjective cognitive difficulties related to neurological disorders.

INTRODUCTION: Digitalization has changed working life and increased cognitive demands on employees in general. Nevertheless, the consequences for employees with cognitive impairments and subjective cognitive difficulties are to a large extent unexplored. The aim of this study was to explore and describe how employees with subjective cognitive difficulties who are performing digital work tasks experience their vocational situation and how this situation influences their everyday life. METHODS: A qualitative, descriptive, multiple-case study was designed. Self-reports, assessments and qualitative interviews were used to collect data from the seven participants with neurological disorders. The data were analysed using pattern matching. FINDINGS: The analysed data formed four categories conceptualized as "Working to my full potential", "Working, but it is largely up to me", "Working at the expense of everyday life" and "Working without known difficulties", and these categories included one to four subcategories. CONCLUSION: Managing subjective cognitive difficulties in vocational situations and everyday life was challenging in a digitalized working life for participants with neurological disorders. To provide equal access to preventive measures and rehabilitation and a sustainable working life, it is important to investigate the influence of subjective cognitive difficulties systematically on work, everyday life and management strategies in people with neurological disorders in digitalized work.

Disability and life satisfaction in neurological disorders: The role of depression and perceived cognitive difficulties.

BACKGROUND: This study assessed factors associated with disability and life satisfaction in a large cohort of 2246 Australian adults with neurological disorders who completed an online survey of mental health and wellbeing. It was hypothesised that depressive symptoms and perceived cognitive difficulties would be significantly associated with both outcomes, even after controlling for significant demographic/medical covariates (e.g., age, marital-status, employment, multi-morbidity, medication). Differences in profiles of four neurological subgroups (i.e., multiple sclerosis; n = 738, epilepsy; n = 672, Parkinson's disease; n = 263, and Acquired Bran Injury; n = 278) were explored. METHODS: Multiple hierarchical linear regressions were run using cross-sectional data. RESULTS: Depressive symptoms made a significant and large unique contribution to higher levels of disability (ß = 0.333, p < .001), and poorer life satisfaction (ß = -0.434, p < .001), in the overall sample and across all four neurological subgroups (ß = 0.349 to 0.513, p < .001) Greater perceived cognitive difficulties were associated with disability in the overall sample (ß = 0.318, p < .001) and across all neurological subgroups (ß = 0.231 to 0.354, p < .001), but only life satisfaction in epilepsy (ß = -0.107, p = 006). CONCLUSIONS: The findings underscore the importance of managing psychological/neuropsychiatric comorbidities in neurological disorders.

Congenital Zika Infection and the Risk of Neurodevelopmental, Neurological, and Urinary Track Disorders in Early Childhood. A Systematic Review.

It was late 2015 when Northeast Brazil noticed a worrying increase in neonates born with microcephaly and other congenital malformations. These abnormalities, characterized by an abnormally small head and often neurological impairment and later termed Congenital Zika Syndrome, describe the severity of neurodevelopmental and nephrological outcomes in early childhood, and the implication of microcephaly at birth. The purpose of the study was to describe the neurodevelopmental outcomes in children exposed to Zika virus during fetal life, with and without microcephaly at birth. The systematic review included research studies about the neurodevelopmental outcomes with and without microcephaly, as well as nephrological outcomes in early childhood. We searched PubMed, Crossref, PsycINFO, Scopus, and Google Scholar publications and selected 19 research articles published from 2018 to 2021. Most studies have linked the severity of microcephaly in childbirth to the neurodevelopmental and urinary outcomes in early childhood. However, most children without microcephaly at birth develop typically, while others may be at risk for language impairment.

Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity.

BACKGROUND: Non-Celiac Wheat Sensitivity (NCWS) is characterized by both intestinal and extra-intestinal symptoms. The study aims to investigate the frequency of neuropsychiatric manifestations in NCWS patients and identify their clinical and demographic characteristics. METHODS: 278 clinical records of NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge between 2006 and 2020, were retrospectively revised. Fifty-two patients with Celiac Disease (CD) and 54 patients with Irritable Bowel Syndrome (IBS) served as controls. RESULTS: 87% of the NCWS patients had an IBS-like clinical presentation. The NCWS group showed a longer duration of symptoms, a higher frequency of positive serum anti-nuclear antibodies than CD and IBS patients, and a higher frequency of DQ2/DQ8 haplotypes and duodenal mucosa lymphocytosis than IBS controls. In addition, 50% of NCWS patients showed neuropsychiatric manifestations, while lower percentages were observed in CD (25%) and IBS (28%) controls. Neuropsychiatric symptoms in NCWS were more frequently associated with the male sex, longer duration of symptoms, and IBS-diarrhea-like clinical presentation. CONCLUSIONS: Our data suggest that in patients with IBS-like symptoms and neuropsychiatric manifestations of unknown cause, it could be useful to investigate a correlation of these symptoms with wheat ingestion to identify NCWS patients with this 'atypical' manifestation.

COVID-19-related neuropathology and microglial activation in elderly with and without dementia.

The actual role of SARS-CoV-2 in brain damage remains controversial due to lack of matched controls. We aim to highlight to what extent is neuropathology determined by SARS-CoV-2 or by pre-existing conditions. Findings of 9 Coronavirus disease 2019 (COVID-19) cases and 6 matched non-COVID controls (mean age 79 y/o) were compared. Brains were analyzed through immunohistochemistry to detect SARS-CoV-2, lymphocytes, astrocytes, endothelium, and microglia. A semi-quantitative scoring was applied to grade microglial activation. Thal-Braak stages and the presence of small vessel disease were determined in all cases. COVID-19 cases had a relatively short clinical course (0-32 days; mean: 10 days), and did not undergo mechanical ventilation. Five patients with neurocognitive disorder had delirium. All COVID-19 cases showed non-SARS-CoV-2-specific changes including hypoxic-agonal alterations, and a variable degree of neurodegeneration and/or pre-existent SVD. The neuroinflammatory picture was dominated by ameboid CD68 positive microglia, while only scant lymphocytic presence and very few traces of SARS-CoV-2 were detected. Microglial activation in the brainstem was significantly greater in COVID-19 cases (p = 0.046). Instead, microglial hyperactivation in the frontal cortex and hippocampus was clearly associated to AD pathology (p = 0.001), regardless of the SARS-CoV-2 infection. In COVID-19 cases complicated by delirium (all with neurocognitive disorders), there was a significant enhancement of microglia in the hippocampus (p = 0.048). Although higher in cases with both Alzheimer's pathology and COVID-19, cortical neuroinflammation is not related to COVID-19 per se but mostly to pre-existing neurodegeneration. COVID-19 brains seem to manifest a boosting of innate immunity with microglial reinforcement, and adaptive immunity suppression with low number of brain lymphocytes probably related to systemic lymphopenia. Thus, no neuropathological evidence of SARS-CoV-2-specific encephalitis is detectable. The microglial hyperactivation in the brainstem, and in the hippocampus of COVID-19 patients with delirium, appears as a specific topographical phenomenon, and probably represents the neuropathological basis of the "COVID-19 encephalopathic syndrome" in the elderly.

Sustained Dysbiosis and Decreased Fecal Short-Chain Fatty Acids after Traumatic Brain Injury and Impact on Neurologic Outcome.

Traumatic brain injury (TBI) alters microbial populations present in the gut, which may impact healing and tissue recovery. However, the duration and impact of these changes on outcome from TBI are unknown. Short-chain fatty acids (SCFAs), produced by bacterial fermentation of dietary fiber, are important signaling molecules in the microbiota gut-brain axis. We hypothesized that TBI would lead to a sustained reduction in SCFA producing bacteria, fecal SCFAs concentration, and administration of soluble SCFAs would improve functional outcome after TBI. Adult mice (n = 10) had the controlled cortical impact (CCI) model of TBI performed (6 m/sec, 2-mm depth, 50-msec dwell). Stool samples were collected serially until 28 days after CCI and analyzed for SCFA concentration by high-performance liquid chromatography-mass spectrometry/mass spectrometry and microbiome analyzed by 16S gene sequencing. In a separate experiment, mice (n = 10/group) were randomized 2 weeks before CCI to standard drinking water or water supplemented with the SCFAs acetate (67.5 mM), propionate (25.9 mM), and butyrate (40 mM). Morris water maze performance was assessed on post-injury Days 14-19. Alpha diversity remained stable until 72 h, at which point a decline in diversity was observed without recovery out to 28 days. The taxonomic composition of post-TBI fecal samples demonstrated depletion of bacteria from Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae families, and enrichment of bacteria from the Verrucomicrobiaceae family. Analysis from paired fecal samples revealed a reduction in total SCFAs at 24 h and 28 days after TBI. Acetate, the most abundant SCFA detected in the fecal samples, was reduced at 7 days and 28 days after TBI. SCFA administration improved spatial learning after TBI versus standard drinking water. In conclusion, TBI is associated with reduced richness and diversity of commensal microbiota in the gut and a reduction in SCFAs detected in stool. Supplementation of soluble SCFAs improves spatial learning after TBI.

Associations of AT(N) biomarkers with neuropsychiatric symptoms in preclinical Alzheimer's disease and cognitively unimpaired individuals.

The development of in vivo biomarkers of Alzheimer's disease (AD) has advanced the diagnosis of AD from a clinical syndrome to a biological construct. The preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired individuals. While neuropsychiatric symptoms (NPS) are non-cognitive symptoms that are increasingly recognized as early manifestations of AD, the associations of NPS with AD pathophysiology in preclinical AD remain unclear. Here, we review the associations between NPS and AD biomarkers amyloid-ß (Aß), tau and neurodegeneration in preclinical AD and cognitively-unimpaired individuals in 19 eligible English-language publications (8 cross-sectional studies, 10 longitudinal, 1 both cross-sectional and longitudinal). The cross-sectional studies have consistently shown that NPS, particularly depressive and anxiety symptoms, are associated with higher Aß. The longitudinal studies have suggested that greater NPS are associated with higher Aß and cognitive decline in cognitively unimpaired subjects over time. However, most of the studies have either cross-sectionally or longitudinally shown no association between NPS and tau pathology. For the association of NPS and neurodegeneration, two studies have shown that the cerebrospinal fluid total-tau is linked to longitudinal increase in NPS and that the NPS may predict longitudinal metabolic decline in preclinical AD, respectively. However, evidence for the association between atrophy and NPS in preclinical AD is less consistent. Therefore, future longitudinal studies with well-designed methodologies and NPS measurements are required not only to determine the relationship among AT(N) biomarkers, NPS and cognitive decline, but also to elucidate the contribution of comorbid pathology to preclinical AD.