Current Opinion in Neurology最新文献

Purpose of review: This review aims to explore the use of patient-reported outcome measures (PROMs) in migraine. Traditionally assessed through specific features, recent adoption of PROMs allows for a more objective and quantifiable evaluation. PROMs, which are standardized questionnaires collecting health information directly from a patients' perspective, cover various aspects, including migraine specific aspects. The review focuses on delineating the applications and interpretation of commonly used PROMs in migraine research, with an emphasis on their integration in clinical care.

Recent findings: Generic and migraine-specific PROMs play a crucial role in clinical research, particularly in assessing health-related quality of life, disability, impact, and associated comorbidities. Some of these measures are strongly recommended to be used by the International Guidelines and are, in fact, mandated by the FDA for product labeling. Recently, there has been an expansion in the use of PROMs to assess migraine in diverse populations, in particular pediatric patients. However, the application of these measures in clinical care shows considerable heterogeneity, and some have not been validated specifically for migraine. The existing multitude of PROMs, coupled with ongoing development of new ones to better capture patient concerns, creates complexity in their research and clinical application. To address these challenges, it becomes imperative to streamline their use, focusing on those that are more validated and better aligned with the patients' perspective including different populations' needs.

Summary: The utilization of PROMs in evaluating migraine enables a more holistic assessment, helps quantify the impact of the disease facilitating change measurement, improves communication between healthcare providers and patients and, guides treatment decisions for improved outcomes. However, the increasing number of PROMs questionnaires, underscores the importance of validating these tools for migraine and, the dynamic nature of the disease makes it relevant to decide with whom, why and when these should be used.

Purpose of review: We summarize the recent discoveries on genetic predisposition to autoimmune encephalitis and paraneoplastic neurological syndromes (PNS), emphasizing clinical and pathophysiological implications.

Recent findings: The human leukocyte antigen (HLA) is the most studied genetic factor in autoimmune encephalitis and PNS. The HLA haplotype 8.1, which is widely known to be related to systemic autoimmunity, has been only weakly associated with a few types of autoimmune encephalitis and PNS. However, the strongest and most specific associations have been reported in a subgroup of autoimmune encephalitis that comprises antileucine-rich glioma-inactivated 1 (LGI1) limbic encephalitis, associated with DRB1∗07 : 01 , anticontactin-associated protein-like 2 (CASPR2) limbic encephalitis, associated with DRB1∗11 : 01 , and anti-IgLON5 disease, associated with DRB1∗10 : 01∼DQA1∗01∼DQB1∗05 . Non-HLA genes have been poorly investigated so far in autoimmune encephalitis, mainly in those lacking HLA associations such as anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, with only a few genome-wide association studies (GWAS) reporting equivocal results principally limited by small sample size.

Summary: Genetic predisposition seems to be driven mostly by HLA in a group of autoimmune encephalitis characterized by being nonparaneoplastic and having predominantly IgG4 autoantibodies. The contribution of non-HLA genes, especially in those diseases lacking known or strong HLA associations, will require large cohorts enabling GWAS to be powerful enough to render meaningful results.

Purpose of review: To describe relevant advances in nonparaneoplastic autoimmune cerebellar ataxias (ACA) with neuronal antibodies.

Recent findings: Apart from metabotropic glutamate receptor 1(mGluR1) antibodies, in recent years, the number of neuronal antibodies against surface antigens in ACA has increased with the description of glutamate kainate receptor subunit 2 (GluK2) antibodies in young patients with cerebellitis. Around 20% of patients with contactin-associated protein-like 2 (CASPR2) encephalitis also present prominent cerebellar ataxia. However, isolate cerebellar ataxia is unusual (<4%). Outcome in patients with neuronal antibodies against surface antigens remains suboptimal despite the cerebellar ataxia probably is antibody-mediated.Concerning neuronal antibodies against intracellular antigens, up to 25% of patients with glutamic acid decarboxylase (GAD) antibodies present transient episodes of vertigo or diplopia that antedate the development of the ACA. There is in-vitro evidence that septin-5 is partially exposed to the membrane and the antibodies may interfere with septin-5 function. The clinical significance of the remaining antibodies against intracellular antigens remains unclear.

Summary: The number of antibodies against surface antigens is increasing in ACA, but the response to the immunotherapy remains suboptimal. More studies are needed to clarify the role of most of the antibodies against intracellular antigens described in these patients.

Purpose of review: The increasing recognition and diagnosis of autoimmune encephalitis (AE) and paraneoplastic neurological syndromes (PNS) is partly due to neural autoantibody testing and discovery. The past two decades witnessed an exponential growth in the number of identified neural antibodies. This review aims to summarize recent rare antibody discoveries in the context of central nervous system (CNS) autoimmunity and evaluate the ongoing debate about their utility.

Recent findings: In the last 5 years alone 15 novel neural autoantibody specificities were identified. These include rare neural antibody biomarkers of autoimmune encephalitis, cerebellar ataxia or other movement disorders, including multifocal presentations.

Summary: Although the clinical applications of these rare antibody discoveries may be limited by the low number of positive cases, they still provide important diagnostic, prognostic, and therapeutic insights.

Purpose of review: We discuss racial and ethnic disparities in multiple sclerosis (MS), outcomes, and social determinants of health (SDoH). We also provide essential considerations needed to bridge the gap in inequalities, including broader representation of racial and ethnic people in clinical trials and research in general and the inclusion of better measures of living conditions.

Recent findings: The incidence and prevalence of MS have become more diverse in the USA. There is increased recognition that racial and ethnic health disparities and inequities exist due to adverse social conditions. Clinical trials have failed to be inclusive and diverse. Training in health disparity is an essential priority of funding sources, and designing clinical trials that consider the barriers these populations face can close significant gaps.

Summary: The incidence, prevalence, and awareness of MS have seen an incline in diverse racial and ethnic populations. Health disparities exist in MS with Black, Hispanic, and indigenous populations appearing to have worse outcomes. SDoH play a significant role in causing these health disparities. Accessibility to clinical trials and treatment are barriers these populations face. Strategic and earnest interventions considering SDoH are critically needed to develop solutions that collectively improve health and MS care for all.

Purpose of review: Despite availability of high-efficacy therapies for multiple sclerosis (MS), many patients experience significant disability worsening due to limited effects of currently available drugs on central nervous system (CNS)-compartmentalized inflammation. Bruton tyrosine kinase (BTK) is an intracellular signaling molecule involved in regulation of maturation, survival, migration, and activation of B cells and microglia, which are central players in the immunopathogenesis of progressive MS. Therefore, CNS-penetrant BTK inhibitors may better prevent disease progression by targeting immune cells on both sides of the blood-brain barrier. This review gives an overview on the preliminary results of clinical trials.

Recent findings: Currently, the efficacy and safety of six BTK inhibitors are being evaluated in clinical trials in patients with relapsing and progressive MS. Evobrutinib, tolebrutinib and fenebrutinib have shown efficacy and safety in relapsing MS in phase 2 studies, and evobrutinib and tolebrutinib in their extension studies up to 3-5 years. However, evobrutinib failed to distinguish itself from the comparator drug teriflunomide in reduction of relapse rate (primary end point) in two phase 3 studies in relapsing MS.

Summary: Inhibition of BTK has emerged as a promising therapeutic approach to target the CNS-compartmentalized inflammation. Results from phase 3 clinical trials will shed light on differences in efficacy and safety of BTK inhibitors and its potential role in the future MS landscape.

Purpose of review: Purpose of this review is to update the ongoing work in the field of glymphatic and neurodegenerative research and to highlight focus areas that are particularly promising.

Recent findings: Multiple reports have over the past decade documented that glymphatic fluid transport is broadly suppressed in neurodegenerative diseases. Most studies have focused on Alzheimer's disease using a variety of preclinical disease models, whereas the clinical work is based on various neuroimaging approaches. It has consistently been reported that brain fluid transport is impaired in patients suffering from Alzheimer's disease compared with age-matched control subjects.

Summary: An open question in the field is to define the mechanistic underpinning of why glymphatic function is suppressed. Other questions include the opportunities for using glymphatic imaging for diagnostic purposes and in treatment intended to prevent or slow Alzheimer disease progression.

Purpose of review: Clinical electroencephalography (EEG) is a conservative medical field. This explains likely the significant gap between clinical practice and new research developments. This narrative review discusses possible causes of this discrepancy and how to circumvent them. More specifically, we summarize recent advances in three applications of clinical EEG: source imaging (ESI), high-frequency oscillations (HFOs) and EEG in critically ill patients.

Recent findings: Recently published studies on ESI provide further evidence for the accuracy and clinical utility of this method in the multimodal presurgical evaluation of patients with drug-resistant focal epilepsy, and opened new possibilities for further improvement of the accuracy. HFOs have received much attention as a novel biomarker in epilepsy. However, recent studies questioned their clinical utility at the level of individual patients. We discuss the impediments, show up possible solutions and highlight the perspectives of future research in this field. EEG in the ICU has been one of the major driving forces in the development of clinical EEG. We review the achievements and the limitations in this field.

Summary: This review will promote clinical implementation of recent advances in EEG, in the fields of ESI, HFOs and EEG in the intensive care.