Painful Eyes in Neurology Clinic: A Guide for Neurologists.

Eye pain is a common complaint among patients presenting to the neurology clinic. It can be related to neurologic diseases, but it can also be a localized eye condition. Such disorders can be misleading, as their benign appearance might mask more grave underlying conditions, potentially leading to misdiagnoses or delayed treatment. Clinicians should be aware of the specific neurologic or systemic disorders (eg, demyelinating diseases or vascular abnormalities) that might first manifest as eye pain. Formal ophthalmic consultation is recommended for patients presenting with eye pain as the predominant complaint especially when red flags for more serious pathology are present.

Recent advances in understanding the neurobiology of pediatric functional neurological disorder.

INTRODUCTION: Functional neurological disorder (FND) is a neuropsychiatric disorder that manifests in a broad array of functional motor, sensory, or cognitive symptoms, which arise from complex interactions between brain, mind, body, and context. Children with FND make up 10%-20% of presentations to neurology services in children's hospitals and up to 20% of adolescents admitted to hospital for the management of intractable seizures. AREAS COVERED: The current review focuses on the neurobiology of pediatric FND. The authors present an overview of the small but growing body of research pertaining to the biological, emotion-processing, cognitive, mental health, physical health, and social system levels. EXPERT OPINION: Emerging research suggests that pediatric FND is underpinned by aberrant changes within and between neuron-glial (brain) networks, with a variety of factors - on multiple system levels - contributing to brain network changes. In pediatric practice, adverse childhood experiences (ACEs) are commonly reported, and activation or dysregulation of stress-system components is a frequent finding. Our growing understanding of the neurobiology of pediatric FND has yielded important flow-on effects for assessing and diagnosing FND, for developing targeted treatment interventions, and for improving the treatment outcomes of children and adolescents with FND.

Disparities in Genetic Testing for Neurologic Disorders.

BACKGROUND AND OBJECTIVES: Genetic testing is now the standard of care for many neurologic conditions. Health care disparities are unfortunately widespread in the US health care system, but disparities in the utilization of genetic testing for neurologic conditions have not been studied. We tested the hypothesis that access to and results of genetic testing vary according to race, ethnicity, sex, socioeconomic status, and insurance status for adults with neurologic conditions. METHODS: We analyzed retrospective data from patients who underwent genetic evaluation and testing through our institution's neurogenetics program. We tested for differences between demographic groups in 3 steps of a genetic evaluation pathway: (1) attending a neurogenetic evaluation, (2) completing genetic testing, and (3) receiving a diagnostic result. We compared patients on this genetic evaluation pathway with the population of all neurology outpatients at our institution, using univariate and multivariable logistic regression analyses. RESULTS: Between 2015 and 2022, a total of 128,440 patients were seen in our outpatient neurology clinics and 2,540 patients underwent genetic evaluation. Black patients were less than half as likely as White patients to be evaluated (odds ratio [OR] 0.49, p < 0.001), and this disparity was similar after controlling for other demographic factors in multivariable analysis. Patients from the least wealthy quartile of zip codes were also less likely to be evaluated (OR 0.67, p < 0.001). Among patients who underwent evaluation, there were no disparities in the likelihood of completing genetic testing, nor in the likelihood of a diagnostic result after adjusting for age. Analyses restricted to specific indications for genetic testing supported these findings. DISCUSSION: We observed unequal utilization of our clinical neurogenetics program for patients from marginalized and minoritized demographic groups, especially Black patients. Among patients who do undergo evaluation, all groups benefit similarly from genetic testing when it is indicated. Understanding and removing barriers to accessing genetic testing will be essential to health care equity and optimal care for all patients with neurologic disorders.

Anger regulation in patients with functional neurological disorder: A systematic review.

BACKGROUND: Functional neurological disorder (FND) has been associated with predisposing psychological factors, including dysregulation of anger-related processes. This paper provides a systematic review of the literature on anger regulation in FND. We evaluated anger-related research on patient self-report, observational, and laboratory based measures in FND. The review also addresses adverse childhood experiences and their relation with anger regulation, and the effects of therapies targeting anger regulation in FND. METHODS: MEDLINE, EMBASE, and PsycINFO were searched for both quantitative and qualitative research, published in a peer-reviewed journal with a sample size of at least 5 (registered under Prospero protocol CRD42022314340). RESULTS: A total of 2200 articles were identified. After screening, 54 studies were included in this review (k = 20 questionnaire-based studies, k = 12 laboratory studies, k = 21 using other methods, and k = 1 used both questionnaires and other methods) representing data of 2502 patients with FND. Questionnaire-based studies indicated elevated levels of state anger and trait hostility in patients with FND. Laboratory studies showed a higher tendency to avoid social threat cues, attentional bias towards angry faces, difficulties reliving anger, and preoccupation with frustrating barriers among FND patients versus controls. No specific childhood experiences were identified related to anger regulation in FND, and too few small and uncontrolled studies were available (k = 2) to assess the effects of anger-related interventions in FND. The overall quality of the studies was fair (k = 31) to poor (k = 18). Five studies (k = 5) were rated as having a good quality. CONCLUSIONS: This review suggests that patients with FND have maladaptive anger regulation compared to individuals without FND. The findings also highlight the need for further research on the prevalence and consequences of anger-related processes in the development, diagnosis and treatment of FND.

Symptom Management in Children Who Are Neurologically Impaired for the Primary Care Medical Home.

Children with neurologic impairment are a growing population of pediatric patients who require care from a large team of physicians to maintain their health. These children often have similar clinical patterns and symptoms that occur because of their neurologic impairment. Families often seek care first from their primary care home to identify and guide initial steps in management. Identifying the symptoms outlined in the 4 cases in this article will help alleviate consequences of delayed care for these patients and provide opportunities for shared decision-making with the family's goals of care for their child. [Pediatr Ann. 2024;53(3):e82-e87.].

Recommendations for optimal interdisciplinary management and healthcare settings for patients with rare neurological diseases.

BACKGROUND: In 2017, the German Academy for Rare Neurological Diseases (Deutsche Akademie für Seltene Neurologische Erkrankungen; DASNE) was founded to pave the way for an optimized personalized management of patients with rare neurological diseases (RND) in all age groups. Since then a dynamic national network for rare neurological disorders has been established comprising renowned experts in neurology, pediatric neurology, (neuro-) genetics and neuroradiology. DASNE has successfully implemented case presentations and multidisciplinary discussions both at yearly symposia and monthly virtual case conferences, as well as further educational activities covering a broad spectrum of interdisciplinary expertise associated with RND. Here, we present recommendation statements for optimized personalized management of patients with RND, which have been developed and reviewed in a structured Delphi process by a group of experts. METHODS: An interdisciplinary group of 37 RND experts comprising DASNE experts, patient representatives, as well as healthcare professionals and managers was involved in the Delphi process. First, an online collection was performed of topics considered relevant for optimal patient care by the expert group. Second, a two-step Delphi process was carried out to rank the importance of the selected topics. Small interdisciplinary working groups then drafted recommendations. In two consensus meetings and one online review round these recommendations were finally consented. RESULTS: 38 statements were consented and grouped into 11 topics: health care structure, core neurological expertise and core mission, interdisciplinary team composition, diagnostics, continuous care and therapy development, case conferences, exchange / cooperation between Centers for Rare Diseases and other healthcare partners, patient advocacy group, databases, translation and health policy. CONCLUSIONS: This German interdisciplinary Delphi expert panel developed consented recommendations for optimal care of patients with RND in a structured Delphi process. These represent a basis for further developments and adjustments in the health care system to improve care for patients with RND and their families.

Flexible neural probes: a review of the current advantages, drawbacks, and future demands. / 柔性神经探针：当前的优点、缺点及未来需求.

Brain diseases affect millions of people and have a huge social and economic impact. The use of neural probes for studies in animals has been the main approach to increasing knowledge about neural network functioning. Ultimately, neuroscientists are trying to develop new and more effective therapeutic approaches to treating neurological disorders. The implementation of neural probes with multifunctionalities (electrical, optical, and fluidic interactions) has been increasing in the last few years, leading to the creation of devices with high temporal and spatial resolution. Increasing the applicability of, and elements integrated into, neural probes has also led to the necessity to create flexible interfaces, reducing neural tissue damage during probe implantation and increasing the quality of neural acquisition data. In this paper, we review the fabrication, characterization, and validation of several types of flexible neural probes, exploring the main advantages and drawbacks of these devices. Finally, future developments and applications are covered. Overall, this review aims to present the currently available flexible devices and future appropriate avenues for development as possible guidance for future engineered devices.

A Web-Based Educational Module Using Clinical Neuroscience to Deliver the Diagnosis of Functional Neurological Disorder.

Neuroscience-based patient education has become an evidence-based strategy for enhancing chronic pain treatment. Advances in understanding the neuroscience of functional neurological disorder (FND) may allow similar approaches to be developed and disseminated to clinicians, given the public health need for greater provider awareness and expertise around the condition. Accordingly, the authors developed an online video module for clinicians that delivers neuroscience-based psychoeducation for FND and assessed whether the intervention would be associated with changes in clinicians' perception of FND patients and knowledge about the condition. The online intervention consisted of a 20-minute video module, including an 8-minute scripted role-play that modeled neuroscience-informed diagnosis delivery. Pre- and postintervention questionnaires were embedded into the online module and included a self-assessment of FND-related perceptions and knowledge and a multiple-choice assessment of retention of the neuroscience-based content. Wilcoxon signed-rank tests and McNemar's tests were used for statistical analyses. Of the 103 individuals who submitted surveys, 40 participants provided a complete data set from before and after the intervention. Following the intervention, self-assessment items showed respondents had significantly greater comfort with diagnosis delivery and treatment options and decreased negative perception of FND patients. The percentage of correct responses on a multiple-choice assessment regarding the functional neuroanatomy of FND was significantly increased. In summary, the online neuroscience-based educational intervention was effective for increasing clinician knowledge about FND and comfort with diagnosis delivery and treatment options. Implementing web-based formats may be a viable and cost-effective approach to disseminating knowledge and basic clinical skills in the care of patients with FND.

Potential Neurologic Manifestations of COVID-19 Infection in Neonates.

In contrast to adults, neonates and infants with coronavirus disease 2019 (COVID-19) infection have milder symptoms and are less likely to require hospitalization. However, some neonates with COVID-19 can present with significant symptoms. Recent evidence suggests that neurologic manifestations of neonatal COVID-19 infection may be higher than initially thought. In this comprehensive review of the current literature, we summarize the clinical, laboratory, and radiologic findings, as well as potential management strategies for COVID-19-related neurologic illness in neonates. Although the growing brain may be affected by neurologic disease associated with COVID-19 infection, the few published studies on the long-term outcomes after COVID-19 infection in neonates and infants provide conflicting results. Larger collaborative clinical studies are needed to determine whether COVID-19 infection in neonates has long-term neurodevelopmental outcomes.

Exosomes: potential targets for the diagnosis and treatment of neuropsychiatric disorders.

The field of neuropsychiatry is considered a middle ground between neurological and psychiatric disorders, thereby bridging the conventional boundaries between matter and mind, consciousness, and function. Neuropsychiatry aims to evaluate and treat cognitive, behavioral, and emotional disorders in individuals with neurological conditions. However, the pathophysiology of these disorders is not yet fully understood, and objective biological indicators for these conditions are currently lacking. Treatment options are also limited due to the blood-brain barrier, which results in poor treatment effects. Additionally, many drugs, particularly antipsychotic drugs, have adverse reactions, which make them difficult to tolerate for patients. As a result, patients often abandon treatment owing to these adverse reactions. Since the discovery of exosomes in 1983, they have been extensively studied in various diseases owing to their potential as nanocellulators for information exchange between cells. Because exosomes can freely travel between the center and periphery, brain-derived exosomes can reflect the state of the brain, which has considerable advantages in diagnosis and treatment. In addition, administration of engineered exosomes can improve therapeutic efficacy, allow lesion targeting, ensure drug stability, and prevent systemic adverse effects. Therefore, this article reviews the source and biological function of exosomes, relationship between exosomes and the blood-brain barrier, relationship between exosomes and the pathological mechanism of neuropsychiatric disorders, exosomes in the diagnosis and treatment of neuropsychiatric disorders, and application of engineered exosomes in neuropsychiatric disorders.

Neurological Complications Caused by Human Immunodeficiency Virus (HIV) and Associated Opportunistic Co-infections: A Review on their Diagnosis and Therapeutic Insights.

Neurocognitive disorders associated with human immunodeficiency virus (HIV) infected individuals increase the risk of mortality and morbidity that remain a prevalent clinical complication even in the antiretroviral therapy era. It is estimated that a considerable number of people in the HIV community are developing neurological complications at their early stages of infection. The daily lives of people with chronic HIV infections are greatly affected by cognitive declines such as loss of attention, learning, and executive functions, and other adverse conditions like neuronal injury and dementia. It has been found that the entry of HIV into the brain and subsequently crossing the blood-brain barrier (BBB) causes brain cell damage, which is the prerequisite for the development of neurocognitive disorders. Besides the HIV replication in the central nervous system and the adverse effects of antiretroviral therapy on the BBB, a range of opportunistic infections, including viral, bacterial, and parasitic agents, augment the neurological complications in people living with HIV (PLHIV). Given the immuno-compromised state of PLHIV, these co-infections can present a wide range of clinical syndromes with atypical manifestations that pose challenges in diagnosis and clinical management, representing a substantial burden for the public health system. Therefore, the present review narrates the neurological complications triggered by HIV and their diagnosis and treatment options. Moreover, coinfections that are known to cause neurological disorders in HIV infected individuals are highlighted.

Genetic testing in adults with neurologic disorders: indications, approach, and clinical impacts.

The role of genetic testing in neurologic clinical practice has increased dramatically in recent years, driven by research on genetic causes of neurologic disease and increased availability of genetic sequencing technology. Genetic testing is now indicated for adults with a wide range of common neurologic conditions. The potential clinical impacts of a genetic diagnosis are also rapidly expanding, with a growing list of gene-specific treatments and clinical trials, in addition to important implications for prognosis, surveillance, family planning, and diagnostic closure. The goals of this review are to provide practical guidance for clinicians about the role of genetics in their practice and to provide the neuroscience research community with a broad survey of current progress in this field. We aim to answer three questions for the neurologist in practice: Which of my patients need genetic testing? What testing should I order? And how will genetic testing help my patient? We focus on common neurologic disorders and presentations to the neurology clinic. For each condition, we review the most current guidelines and evidence regarding indications for genetic testing, expected diagnostic yield, and recommended testing approach. We also focus on clinical impacts of genetic diagnoses, highlighting a number of gene-specific therapies recently approved for clinical use, and a rapidly expanding landscape of gene-specific clinical trials, many using novel nucleotide-based therapeutic modalities like antisense oligonucleotides and gene transfer. We anticipate that more widespread use of genetic testing will help advance therapeutic development and improve the care, and outcomes, of patients with neurologic conditions.

Child-to-adult transition: a survey of current practices within the European Reference Network for Rare Neurological Diseases (ERN-RND).

BACKGROUND: Transition from child-centered to adult-centered healthcare is a gradual process that addresses the medical, psychological, and educational needs of young people in the management of their autonomy in making decisions about their health and their future clinical assistance. This transfer is challenging across all chronic diseases but can be particularly arduous in rare neurological conditions. AIM: To describe the current practice on the transition process for young patients in centers participating in the European Reference Network for Rare Neurological Diseases (ERN-RND). METHODS: Members of the ERN-RND working group developed a questionnaire considering child-to-adult transition issues and procedures in current clinical practice. The questionnaire included 20 questions and was sent to members of the health care providers (HCPs) participating in the network. RESULTS: Twenty ERN-RND members (75% adult neurologists; 25% pediatricians; 5% nurses or study coordinators) responded to the survey, representing 10 European countries. Transition usually occurs between 16 and 18 years of age, but 55% of pediatric HCPs continue to care for their patients until they reach 40 years of age or older. In 5/20 ERN-RND centers, a standardized procedure managing transition is currently adopted, whereas in the remaining centers, the transition from youth to adult service is usually assisted by pediatricians as part of their clinical practice. CONCLUSIONS: This survey demonstrated significant variations in clinical practice between different centers within the ERN-RND network. It provided valuable data on existing transition programs and highlighted key challenges in managing transitions for patients with rare neurological disorders.

eHealth tools to assess the neurological function for research, in absence of the neurologist - a systematic review, part I (software).

BACKGROUND: Neurological disorders remain a worldwide concern due to their increasing prevalence and mortality, combined with the lack of available treatment, in most cases. Exploring protective and risk factors associated with the development of neurological disorders will allow for improving prevention strategies. However, ascertaining neurological outcomes in population-based studies can be both complex and costly. The application of eHealth tools in research may contribute to lowering the costs and increase accessibility. The aim of this systematic review is to map existing eHealth tools assessing neurological signs and/or symptoms for epidemiological research. METHODS: Four search engines (PubMed, Web of Science, Scopus & EBSCOHost) were used to retrieve articles on the development, validation, or implementation of eHealth tools to assess neurological signs and/or symptoms. The clinical and technical properties of the software tools were summarised. Due to high numbers, only software tools are presented here. FINDINGS: A total of 42 tools were retrieved. These captured signs and/or symptoms belonging to four neurological domains: cognitive function, motor function, cranial nerves, and gait and coordination. An additional fifth category of composite tools was added. Most of the tools were available in English and were developed for smartphone device, with the remaining tools being available as web-based platforms. Less than half of the captured tools were fully validated, and only approximately half were still active at the time of data collection. INTERPRETATION: The identified tools often presented limitations either due to language barriers or lack of proper validation. Maintenance and durability of most tools were low. The present mapping exercise offers a detailed guide for epidemiologists to identify the most appropriate eHealth tool for their research. FUNDING: The current study was funded by a PhD position at the University of Groningen. No additional funding was acquired.

Back to the future: encephalitis lethargica as an autoimmune disorder?

More than 100 years after its emergence, the exact pathophysiological mechanisms underlying encephalitis lethargica (EL) are still elusive and awaiting convincing and complete elucidation. This article summarizes arguments proposed over time to support or refute the hypothesis of EL as an autoimmune neuropsychiatric disorder triggered by an infectious process. It also provides a critical evaluation of modern cases labeled as EL and a comprehensive differential diagnosis of autoimmune neurological conditions that could mimic EL. The evidence supporting the autoimmune nature of historical EL is sparse and not entirely convincing. It is possible that autoimmune mechanisms were involved in the pathogenesis of this disease as an idiosyncratic response to a yet unidentified infectious agent in genetically predisposed individuals. Although there has been an increase in the incidence of presumed autoimmune encephalomyelitis since the peak of EL pandemics, most evidence does not support an underlying autoimmune mechanism. There are significant differences between historical and recent EL cases in terms of clinical symptomatology, epidemiology, and neuropathological features, suggesting that they are different entities with only superficial similarity. The term "encephalitis lethargica," still frequently used in the medical literature, should not be used for cases occurring at present in the sporadic form. Historical EL should be kept apart from recent EL, as they differ in important aspects.

Nesfatin-1: A Biomarker and Potential Therapeutic Target in Neurological Disorders.

Nesfatin-1 is a novel adipocytokine consisting of 82 amino acids with anorexic and anti-hyperglycemic properties. Further studies of nesfatin-1 have shown it to be closely associated with neurological disorders. Changes in nesfatin-1 levels are closely linked to the onset, progression and severity of neurological disorders. Nesfatin-1 may affect the development of neurological disorders and can indicate disease evolution and prognosis, thus informing the choice of treatment options. In addition, regulation of the expression or level of nesfatin-1 can improve the level of neuroinflammation, apoptosis, oxidative damage and other indicators. It is demonstrated that nesfatin-1 is involved in neuroprotection and may be a therapeutic target for neurological disorders. In this paper, we will also discuss the role of nesfatin-1 as a biomarker in neurological diseases and its potential mechanism of action in neurological diseases, providing new ideas for the diagnosis and treatment of neurological diseases.

Deciphering a Prodrome: Looking for a Disease in a Haystack

In many chronic diseases, the underlying biological processes begin long before the condition is clinically recognized and diagnosed. After biologic onset of the disease an early, often nonspecific, set of symptoms, or prodrome, may develop before more characteristic symptoms of the disease present. For instance, in Parkinson disease (PD), some of the earliest manifestations, such as smell or taste dysfunction, may occur 2 decades before typical symptoms, such as tremor, appear.1 Generally, the combination of long prodromal phases and nonspecific symptoms hampers early recognition of disease. Recognizing the prodromal phase of a disease in an individual has 2 potential benefits. First, accurate identification of etiologic factors for disease depends on ensuring that the putative exposure preceded biologic onset of the disease and that the identified symptoms are not related to a delay in diagnosis. Therefore, recognition of a prodromal phase may enhance the ability to identify etiologic factors. Second, accurate prediction that an individual is in the prodromal phase of the disease offers the tantalizing possibility that intervention in this phase could prevent or delay evolution of more typical clinical manifestations.2.