Current Neurology and Neuroscience Reports最新文献

Aim: The aging global population poses increasing challenges related to falls and dementia. Early identification of cognitive decline, particularly before noticeable symptoms manifest, is crucial for effective intervention. This review aims to determine the dynamic balance test most closely associated with executive function, potentially serving as a biomarker for cognitive decline.

Recent findings: Based on recent reviews, inhibitory control, a component of executive function, holds significance in influencing balance performance. Studies suggest that the strength of the correlation between cognition and balance tends to be domain-specific and task-specific. Despite these findings, inconclusive evidence remains regarding the connection between executive function and various dynamic balance assessments. Our review identifies a significant association between all dynamic balance tests and executive function, albeit with varying strengths. Notably, a medium effect size is observed for the Timed Up and Go and Functional Reach Test, a small effect size for balance scales, and a strong effect size for postural sway. This review underscores a clear relationship between dynamic balance task performance and executive function. Dynamic posturography holds potential as a clinical biomarker for early detection of cognitive decline, with a note of caution due to observed heterogeneity and limited studies.

Purpose of review: Immune checkpoint inhibitor (ICI) use has been on the rise for treatment of many different malignancies. Subsequently, more has been learned about immune-related adverse events (irAEs) that occur up to 12 months after treatment. This review summarizes the latest findings and management of neuro-ophthalmic associated irAEs.

Recent findings: irAEs can affect the afferent and efferent neuro-ophthalmic pathways, thereby targeting central and peripheral nervous systems. As more cases are being reported, it is becoming apparent that neuro-ophthalmic irAEs often present with atypical features when compared to their spontaneous autoimmune counterparts. These neuro-ophthalmic presentations can also be signs of a more extensive inflammatory process that spans other organ systems, such as myopathies, endocrinopathies, and paraneoplastic syndromes. Awareness of neuro-ophthalmic irAEs and their atypical presentations can lead to early detection, termination of ICI treatment, and immunosuppressant therapy initiation.

Purpose of Review

In recent decades, epidemiological understanding of Parkinson disease (PD) has evolved significantly. Major discoveries in genetics and large epidemiological investigations have provided a better understanding of the genetic, behavioral, and environmental factors that play a role in the pathogenesis and progression of PD. In this review, we provide an epidemiological update of PD with a particular focus on advances in the last five years of published literature.

Recent Findings

We include an overview of PD pathophysiology, followed by a detailed discussion of the known distribution of disease and varied determinants of disease. We describe investigations of risk factors for PD, and provide a critical summary of current knowledge, knowledge gaps, and both clinical and research implications. We emphasize the need to characterize the epidemiology of the disease in diverse populations.

Summary

Despite increasing understanding of PD epidemiology, recent paradigm shifts in the conceptualization of PD as a biological entity will also impact epidemiological research moving forward and guide further work in this field.

Purpose of Review

Immune-mediated necrotizing myopathy (IMNM), characterized by acute or subacute onset, severe weakness, and elevated creatine kinase levels, poses diagnostic and therapeutic challenges. This article provides a succinct overview of IMNM, including clinical features, diagnostic strategies, and treatment approaches.

Recent Findings

Recent insights highlight the different clinical presentations and therapeutic options of IMNM stratified by autoantibody positivity and type. Additionally, recent findings call into question the reported link between statin use and IMNM.

Summary

This review synthesizes current knowledge on IMNM, emphasizing its distinct clinical features and challenging management. The evolving understanding of IMNM underscores the need for a comprehensive diagnostic approach that utilizes a growing range of modalities. Early and aggressive immunomodulatory therapy remains pivotal. Ongoing research aims to refine diagnostic tools and therapeutic interventions for this challenging muscle disorder, underscoring the importance of advancing our understanding to enhance patient outcomes.

Purpose of Review

Glioblastoma remains resistant to most conventional treatments. Despite scientific advances in the past three decades, there has been a dearth of effective new treatments. New approaches to drug delivery and clinical trial design are needed.

Recent Findings

We discuss how the blood–brain barrier and tumor microenvironment pose challenges for development of effective therapies for glioblastoma. Next, we discuss treatments in development that aim to overcome these barriers, including novel drug designs such as nanoparticles and antibody–drug conjugates, novel methods of drug delivery, including convection-enhanced and intra-arterial delivery, and novel methods to enhance drug penetration, such as blood–brain barrier disruption by focused ultrasound and laser interstitial thermal therapy. Lastly, we address future opportunities, positing combination therapy as the best strategy for effective treatment, neoadjuvant and window-of-opportunity approaches to simultaneously enhance therapeutic effectiveness with interrogation of on-treatment biologic endpoints, and adaptive platform and basket trials as imperative for future trial design.

Summary

New approaches to GBM treatment should account for the blood-brain barrier and immunosuppression by improving drug delivery, combining treatments, and integrating novel clinical trial designs.

Purpose of review: This review summarizes previous and ongoing neuroprotection trials in multiple system atrophy (MSA), a rare and fatal neurodegenerative disease characterized by parkinsonism, cerebellar, and autonomic dysfunction. It also describes the preclinical therapeutic pipeline and provides some considerations relevant to successfully conducting clinical trials in MSA, i.e., diagnosis, endpoints, and trial design.

Recent findings: Over 30 compounds have been tested in clinical trials in MSA. While this illustrates a strong treatment pipeline, only two have reached their primary endpoint. Ongoing clinical trials primarily focus on targeting α-synuclein, the neuropathological hallmark of MSA being α-synuclein-bearing glial cytoplasmic inclusions. The mostly negative trial outcomes highlight the importance of better understanding underlying disease mechanisms and improving preclinical models. Together with efforts to refine clinical measurement tools, innovative statistical methods, and developments in biomarker research, this will enhance the design of future neuroprotection trials in MSA and the likelihood of positive outcomes.

Purpose of review: Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disorder of the central nervous system. Age is one of the most important factors in determining MS phenotype. This review provides an overview of how age influences MS clinical characteristics, pathology, and treatment.

Recent findings: New methods for measuring aging have improved our understanding of the aging process in MS. New studies have characterized the molecular and cellular composition of chronic active or smoldering plaques in MS. These lesions are important contributors to disability progression in MS. These studies highlight the important role of immunosenescence and the innate immune system in sustaining chronic inflammation. Given these changes in immune function, several studies have assessed optimal treatment strategies in aging individuals with MS. MS phenotype is intimately linked with chronologic age and immunosenescence. While there are many unanswered questions, there has been much progress in understanding this relationship which may lead to more effective treatments for progressive disease.

Purpose of review: In this review, we will describe current methods for visual field testing in neuro-ophthalmic clinical practice and research, develop terminology that accurately describes patterns of field deficits, and discuss recent advances such as augmented or virtual reality-based perimetry and the use of artificial intelligence in visual field interpretation.

Recent findings: New testing strategies that reduce testing times, improve patient comfort, and increase sensitivity for detecting small central or paracentral scotomas have been developed for static automated perimetry. Various forms of machine learning-based tools such as archetypal analysis are being tested to quantitatively depict and monitor visual field abnormalities in optic neuropathies. Studies show that the combined use of optical coherence tomography and standard automated perimetry to determine the structure-function relationship improves clinical care in neuro-ophthalmic disorders. Visual field assessment must be performed in all patients with neuro-ophthalmic disorders affecting the afferent visual pathway. Quantitative visual field analysis using standard automated perimetry is critical in initial diagnosis, monitoring disease progression, and guidance of therapeutic plans. Visual field defects can adversely impact activities of daily living such as reading, navigation, and driving and thus impact quality of life. Visual field testing can direct appropriate occupational low vision rehabilitation in affected individuals.

Purpose of review: Spinocerebellar ataxias (SCAs) are autosomal dominant degenerative syndromes that present with ataxia and brain stem abnormalities. This review describes the cognitive and behavioral symptoms of SCAs in the context of recent knowledge of the role of the cerebellum in higher intellectual function.

Recent findings: Recent studies suggest that patients with spinocerebellar ataxia can display cognitive deficits even early in the disease. These have been given the term cerebellar cognitive affective syndrome (CCAS). CCAS can be tracked using newly developed rating scales. In addition, patients with spinocerebellar ataxia also display impulsive and compulsive behavior, depression, anxiety, fatigue, and sleep disturbances. This review stresses the importance of recognizing non-motor symptoms in SCAs. There is a pressing need for novel therapeutic interventions to address these symptoms given their deleterious impact on patients' quality of life.

Purpose of review: Papilledema refers to optic disc swelling caused by raised intracranial pressure. This syndrome arises from numerous potential causes, which may pose varying degrees of threat to patients. Manifestations of papilledema range from mild to severe, and early diagnosis is important to prevent vision loss and other deleterious outcomes. The purpose of this review is to highlight the role of optical coherence tomography (OCT) in the diagnosis and management of syndromes of raised intracranial pressure associated with papilledema.

Recent findings: Ophthalmoscopy is an unreliable skill for many clinicians. Optical coherence tomography is a non-invasive ocular imaging technique which may fill a current care gap, by facilitating detection of papilledema for those who cannot perform a detailed fundus examination. Optical coherence tomography may help confirm the presence of papilledema, by detecting subclinical peripapillary retinal nerve fiber layer (pRNFL) thickening that might otherwise be missed with ophthalmoscopy. Enhanced depth imaging (EDI) and swept source OCT techniques may identify optic disc drusen as cause of pseudo-papilledema. Macular ganglion cell inner plexiform layer (mGCIPL) values may provide early signs of neuroaxonal injury in patients with papilledema and inform management for patients with syndromes of raised intracranial pressure. There are well-established advantages and disadvantages of OCT that need to be fully understood to best utilize this method for the detection of papilledema. Overall, OCT may complement other existing tools by facilitating detection of papilledema and tracking response to therapies.  Moving forward, OCT findings may be included in deep learning models to diagnose papilledema.