The Neurocritical Care Examination and Workup.

OBJECTIVE: This article provides an overview of the evaluation of patients in neurocritical care settings and a structured approach to recognizing and localizing acute neurologic emergencies, performing a focused examination, and pursuing workup to identify critical findings requiring urgent management. LATEST DEVELOPMENTS: After identifying and stabilizing imminent threats to survival, including respiratory and hemodynamic compromise, the initial differential diagnosis for patients in neurocritical care is built on a focused history and clinical examination, always keeping in mind critical "must-not-miss" pathologies. A key priority is to identify processes warranting time-sensitive therapeutic interventions, including signs of elevated intracranial pressure and herniation, acute neurovascular emergencies, clinical or subclinical seizures, infections of the central nervous system, spinal cord compression, and acute neuromuscular respiratory failure. Prompt neuroimaging to identify structural abnormalities should be obtained, complemented by laboratory findings to assess for underlying systemic causes. The indication for EEG and lumbar puncture should be considered early based on clinical suspicion. ESSENTIAL POINTS: In neurocritical care, the initial evaluation is often fast paced, requiring assessment and management to happen in parallel. History, clinical examination, and workup should be obtained while considering therapeutic implications and the need for lifesaving interventions.

Neuro-oncologic Emergencies.

OBJECTIVE: Neuro-oncologic emergencies have become more frequent as cancer remains one of the leading causes of death in the United States, second only to heart disease. This article highlights key aspects of epidemiology, diagnosis, and management of acute neurologic complications in primary central nervous system malignancies and systemic cancer, following three thematic classifications: (1) complications that are anatomically or intrinsically tumor-related, (2) complications that are tumor-mediated, and (3) complications that are treatment-related. LATEST DEVELOPMENTS: The main driver of mortality in patients with brain metastasis is systemic disease progression; however, intracranial hypertension, treatment-resistant seizures, and overall decline due to increased intracranial burden of disease are the main factors underlying neurologic-related deaths. Advances in the understanding of tumor-specific characteristics can better inform risk stratification of neurologic complications. Following standardized grading and management algorithms for neurotoxic syndromes related to newer immunologic therapies is paramount to achieving favorable outcomes. ESSENTIAL POINTS: Neuro-oncologic emergencies span the boundaries of subspecialties in neurology and require a broad understanding of neuroimmunology, neuronal hyperexcitability, CSF flow dynamics, intracranial compliance, and neuroanatomy.

[«Digital Postcovid Syndrome¼ - possibilities and limits in digital communication with neurological patients]. / «Digitales Postcovid-Syndrom¼ ­ Möglichkeiten und Grenzen in der digitalisierten Kommunikation mit neurologischen Patienten.

INTRODUCTION: Background: This work deals with the question of which digital touchpoints in the course of a patient journey are desired by neurological patients, important for effective treatment and easy to implement. Methodology: 100 (44 men, 56 women) patients in a neurological practice at three different locations were examined using a written questionnaire with closed questions on topics of online booking, making appointments and reminders via SMS, video consultation with the doctor and chat with the doctor or the medical practice assistant. Results: It was shown that the older a person is, the less they prefer digital booking and consultation and that the more they work, the more they prefer digital booking and consultation and the longer they live in Switzerland, the less they prefer chat advice. Data protection plays a more important role in older patients. Regarding gender no significant differences can be shown. Discussion: The results are in line with a survey conducted by the Swiss Medical Association (Foederatio Medicorum Helveticorum) of 2020, which shows that the population wants to relieve the burden on doctors in administrative tasks through the use of digital solutions considered desirable. In this study, both younger and older patients are very interested in booking appointments online and to receive an appointment reminder via text message. Since older patients tend to prefer conservative booking, a «hybrid model¼ should be offered so that both options are available.

Soft bioelectronics for diagnostic and therapeutic applications in neurological diseases.

Physical and chemical signals in the central nervous system yield crucial information that is clinically relevant under both physiological and pathological conditions. The emerging field of bioelectronics focuses on the monitoring and manipulation of neurophysiological signals with high spatiotemporal resolution and minimal invasiveness. Significant advances have been realized through innovations in materials and structural design, which have markedly enhanced mechanical and electrical properties, biocompatibility, and overall device performance. The diagnostic and therapeutic potential of soft bioelectronics has been corroborated across a diverse array of pre-clinical settings. This review summarizes recent studies that underscore the developments and applications of soft bioelectronics in neurological disorders, including neuromonitoring, neuromodulation, tumor treatment, and biosensing. Limitations and outlooks of soft devices are also discussed in terms of power supply, wireless control, biocompatibility, and the integration of artificial intelligence. This review highlights the potential of soft bioelectronics as a future platform to promote deciphering brain functions and clinical outcomes of neurological diseases.

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.

A machine learning algorithm based on circulating metabolic biomarkers offers improved predictions of neurological diseases.

BACKGROUND AND AIMS: A machine learning algorithm based on circulating metabolic biomarkers for the predictions of neurological diseases (NLDs) is lacking. To develop a machine learning algorithm to compare the performance of a metabolic biomarker-based model with that of a clinical model based on conventional risk factors for predicting three NLDs: dementia, Parkinson's disease (PD), and Alzheimer's disease (AD). MATERIALS AND METHODS: The eXtreme Gradient Boosting (XGBoost) algorithm was used to construct a metabolic biomarker-based model (metabolic model), a clinical risk factor-based model (clinical model), and a combined model for the prediction of the three NLDs. Risk discrimination (c-statistic), net reclassification improvement (NRI) index, and integrated discrimination improvement (IDI) index values were determined for each model. RESULTS: The results indicate that incorporation of metabolic biomarkers into the clinical model afforded a model with improved performance in the prediction of dementia, AD, and PD, as demonstrated by NRI values of 0.159 (0.039-0.279), 0.113 (0.005-0.176), and 0.201 (-0.021-0.423), respectively; and IDI values of 0.098 (0.073-0.122), 0.070 (0.049-0.090), and 0.085 (0.068-0.101), respectively. CONCLUSION: The performance of the model based on circulating NMR spectroscopy-detected metabolic biomarkers was better than that of the clinical model in the prediction of dementia, AD, and PD.

Hook-effect in MAGLUMI immunoassay for serum anti-GAD antibodies in neurological disorders: When "wrong" matrix is the right choice.

Antibodies against glutamic acid decarboxylase (anti-GAD) are a valuable diagnostic tool to detect severe autoimmune conditions as type 1 diabetes mellitus (T1DM) and anti-GAD related neurological disorders, having the latter more often anti-GAD concentrations in serum multiple times higher than in the former. Automated immunoassays, either with ELISA or chemiluminescent technology, are validated for diagnostic use in serum with analytical ranges suitable for T1DM diagnosis. In a patient presenting with a suspected autoimmune ataxia, anti-GAD testing on an automated chemiluminescent immunoassay (CLIA) resulted in slightly abnormal concentrations in serum (39.2 KIU/L) and very high concentrations in CSF (>280 KIU/L), thus prompting to proceed to serum dilutions to exclude a false negative result and a misdiagnosis. Different dilutions of serum resulted in nonlinear concentrations with endpoint result of 276,500 KIU/L at dilution 1:1000. CSF dilution was instead linear with endpoint result of 4050 KIU/L. In this case report we found that anti-GAD testing in CSF was essential to establish the clinical diagnosis and to suspect hook-effect in serum due to the excess of autoantibodies in this severe autoimmune condition.

Understanding Functional Neurological Disorder: Recent Insights and Diagnostic Challenges.

Functional neurological disorder (FND), formerly called conversion disorder, is a condition characterized by neurological symptoms that lack an identifiable organic purpose. These signs, which can consist of motor, sensory, or cognitive disturbances, are not deliberately produced and often vary in severity. Its diagnosis is predicated on clinical evaluation and the exclusion of other medical or psychiatric situations. Its treatment typically involves a multidisciplinary technique addressing each of the neurological symptoms and underlying psychological factors via a mixture of medical management, psychotherapy, and supportive interventions. Recent advances in neuroimaging and a deeper exploration of its epidemiology, pathophysiology, and clinical presentation have shed new light on this disorder. This paper synthesizes the current knowledge on FND, focusing on its epidemiology and underlying mechanisms, neuroimaging insights, and the differentiation of FND from feigning or malingering. This review highlights the phenotypic heterogeneity of FND and the diagnostic challenges it presents. It also discusses the significant role of neuroimaging in unraveling the complex neural underpinnings of FND and its potential in predicting treatment response. This paper underscores the importance of a nuanced understanding of FND in informing clinical practice and guiding future research. With advancements in neuroimaging techniques and growing recognition of the disorder's multifaceted nature, the paper suggests a promising trajectory toward more effective, personalized treatment strategies and a better overall understanding of the disorder.

Neurological Deterioration in Wilson's Disease-Types, Etiology, Course, and Management.

Wilson's disease (WD) is an inherited disorder of copper metabolism in which pathological copper accumulation, mainly in the liver and the brain, leads to hepatic and/or neuropsychiatric signs and symptoms. Chelators and zinc salts can successfully induce negative copper balance in many patients; however, neurological deterioration may still be observed. This phenomenon can be divided into: (1) early 'paradoxical' neurological deterioration, which usually develops in the first 6 months of anti-copper treatment and may be commonly related to drug type, or (2) late neurological deterioration, which mostly occurs after 6 months of treatment and is often related either to non-compliance with treatment, overtreatment resulting in copper deficiency, or adverse drug reactions. Another explanation, especially for early neurological deterioration, is natural WD progression, which can be difficult to differentiate from drug-related deterioration, but usually leads to a worse outcome. There is still no consensus on how to define neurological deterioration in WD using scales or biomarkers, how to distinguish it from the natural disease progression, its risk factors, and optimal management. This narrative review, based on the current literature, aims to provide definitions, prevalence, pathological mechanisms and factors related to neurological deterioration, and also proposes schemes for diagnosis and treatment.

Neurofilaments as biomarkers in neurological disorders - towards clinical application.

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.

The clinical utility and diagnostic implementation of human subject cell transdifferentiation followed by RNA sequencing.

RNA sequencing (RNA-seq) has recently been used in translational research settings to facilitate diagnoses of Mendelian disorders. A significant obstacle for clinical laboratories in adopting RNA-seq is the low or absent expression of a significant number of disease-associated genes/transcripts in clinically accessible samples. As this is especially problematic in neurological diseases, we developed a clinical diagnostic approach that enhanced the detection and evaluation of tissue-specific genes/transcripts through fibroblast-to-neuron cell transdifferentiation. The approach is designed specifically to suit clinical implementation, emphasizing simplicity, cost effectiveness, turnaround time, and reproducibility. For clinical validation, we generated induced neurons (iNeurons) from 71 individuals with primary neurological phenotypes recruited to the Undiagnosed Diseases Network. The overall diagnostic yield was 25.4%. Over a quarter of the diagnostic findings benefited from transdifferentiation and could not be achieved by fibroblast RNA-seq alone. This iNeuron transcriptomic approach can be effectively integrated into diagnostic whole-transcriptome evaluation of individuals with genetic disorders.

Summary of the 2024 Update of the European Association of Urology Guidelines on Neurourology.

BACKGROUND AND OBJECTIVE: Most patients with neurourological disorders require lifelong medical care. The European Association of Urology (EAU) regularly updates guidelines for diagnosis and treatment of these patients. The objective of this review is to provide a summary of the 2024 updated EAU guidelines on neurourology. METHODS: A structured literature review covering the timeframe 2021-2023 was conducted for the guideline update. A level of evidence and a strength rating were assigned for each recommendation on the basis of the literature data. KEY FINDINGS AND LIMITATIONS: Neurological conditions significantly affect urinary, sexual, and bowel function, and lifelong management is required for neurourological patients to maintain their quality of life and prevent urinary tract deterioration. Early diagnosis and effective treatment are key, and comprehensive clinical assessments, including urodynamics, are crucial. Management should be customised to individual needs and should involve a multidisciplinary approach and address sexuality and fertility. Lifelong monitoring and follow-up highlight the importance of continuous care for neurourological patients. CONCLUSIONS AND CLINICAL IMPLICATIONS: The 2024 EAU guidelines on neurourology provide an up-to-date overview of available evidence on diagnosis, treatment, and follow-up for neurourological patients. PATIENT SUMMARY: Neurological disorders very frequently affect the lower urinary tract and sexual and bowel function and patients need lifelong management. We summarise the updated European Association of Urology guidelines on neurourology to provide patients and caregivers with the latest insights for optimal health care support.

From bench to bedside: Overview of magnetoencephalography in basic principle, signal processing, source localization and clinical applications.

Magnetoencephalography (MEG) is a non-invasive technique that can precisely capture the dynamic spatiotemporal patterns of the brain by measuring the magnetic fields arising from neuronal activity along the order of milliseconds. Observations of brain dynamics have been used in cognitive neuroscience, the diagnosis of neurological diseases, and the brain-computer interface (BCI). In this study, we outline the basic principle, signal processing, and source localization of MEG, and describe its clinical applications for cognitive assessment, the diagnoses of neurological diseases and mental disorders, preoperative evaluation, and the BCI. This review not only provides an overall perspective of MEG, ranging from practical techniques to clinical applications, but also enhances the prevalent understanding of neural mechanisms. The use of MEG is expected to lead to significant breakthroughs in neuroscience.

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.

Identification and characterization of repeat expansions in neurological disorders: Methodologies, tools, and strategies.

Tandem repeats are a common, highly polymorphic class of variation in human genomes. Their expansion beyond a pathogenic threshold is a process that contributes to a wide range of neurological and neuromuscular genetic disorders, of which over 60 have been identified to date. The last few years have seen a resurgence in repeat expansion discovery propelled by technological advancements, enabling the identification of over 20 novel repeat expansion disorders. These expansions can occur in coding or non-coding regions of genes, resulting in a range of pathogenic mechanisms. In this article, we review strategies, tools and methods that can be used for efficient detection and characterization of known repeat expansions and identification of new expansion disorders. Features that can be used to prioritize repeat expansions include anticipation, which is characterized by increased severity or earlier onset of symptoms across generations, and founder effects, which contribute to higher prevalence rates in certain populations. Classical technologies such as Southern blotting, repeat-primed polymerase chain reaction (PCR) and long-range PCR can still be used to detect known repeat expansions, although they usually have significant limitations linked to the absence of sequence context. Targeted sequencing of known expansions using either long-range PCR or CRISPR-Cas9 enrichment combined with long-read sequencing or adaptive nanopore sampling are usually better but more expensive alternatives. The development of new bioinformatics tools applied to short-read genome data can now be used to detect repeat expansions either in a targeted manner or at the genome-wide level. In addition, technological advances, particularly long-read technologies such as optical genome mapping (Bionano Genomics), Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio) HiFi sequencing, offer promising avenues for the detection of repeat expansions. Despite challenges in specific DNA extraction requirements, computation resources needed and data interpretation, these technologies have an immense potential to advance our understanding of repeat expansion disorders and improve diagnostic accuracy.

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.

Validation of a Novel Neurologic Assessment Test for Healthcare Staff.

ABSTRACT: BACKGROUND: To measure the effectiveness of an educational intervention, it is essential to develop high-quality, validated tools to assess a change in knowledge or skills after an intervention. An identified gap within the field of neurology is the lack of a universal test to examine knowledge of neurological assessment. METHODS: This instrument development study was designed to determine whether neuroscience knowledge as demonstrated in a Neurologic Assessment Test (NAT) was normally distributed across healthcare professionals who treat patients with neurologic illness. The variables of time, knowledge, accuracy, and confidence were individually explored and analyzed in SAS. RESULTS: The mean (standard deviation) time spent by 135 participants to complete the NAT was 12.9 (3.2) minutes. The mean knowledge score was 39.5 (18.2), mean accuracy was 46.0 (15.7), and mean confidence was 84.4 (24.4). Despite comparatively small standard deviations, Shapiro-Wilk scores indicate that the time spent, knowledge, accuracy, and confidence are nonnormally distributed ( P < .0001). The Cronbach α was 0.7816 considering all 3 measures (knowledge, accuracy, and confidence); this improved to an α of 0.8943 when only knowledge and accuracy were included in the model. The amount of time spent was positively associated with higher accuracy ( r2 = 0.04, P < .05), higher knowledge was positively associated with higher accuracy ( r2 = 0.6543, P < .0001), and higher knowledge was positively associated with higher confidence ( r2 = 0.4348, P < .0001). CONCLUSION: The scores for knowledge, confidence, and accuracy each had a slightly skewed distribution around a point estimate with a standard deviation smaller than the mean. This suggests initial content validity in the NAT. There is adequate initial construct validity to support using the NAT as an outcome measure for projects that measure change in knowledge. Although improvements can be made, the NAT does have adequate construct and content validity for initial use.