Current Opinion in Neurology最新文献

Purpose of review: On World Encephalitis Day 19th February 2025, Encephalitis International launched the World Health Organization technical brief on encephalitis, highlighting the growing public health challenge and need for improved diagnostics. This review summarizes the published literature over the last 18 months on novel methods of identifying the aetiology of neurological infections and existing research gaps.

Recent findings: There is an increased availability and sensitivity of multiplex polymerase chain reaction assays and untargeted metagenomic sequencing in clinical practice. This is contributing to increasing diagnostic yield in suspected neurological infections. Preliminary results suggest that novel serological methods such as phage immunoprecipitation sequencing (Phip-seq) may be useful where molecular approaches are negative.

Summary: Significant progress in improving diagnostics has been made in the last decade. Going forward, multicentre studies and meta-analyses are needed to achieve adequate power in ascertaining the role of novel diagnostic methods in neurological infections. Studies need to investigate the impact on patient management and cost-effectiveness. The role of other omics methods in identifying host biomarkers for utilization in diagnostic algorithms needs further work.

Purpose of review: Neurocysticercosis, the infestation of the human central nervous system by Taenia solium cysts, accounts for a significant burden of neurological disorders in endemic regions. It is a neglected tropical disease and, hence, often overlooked. However, its importance is underscored by the high burden of epilepsy in endemic regions and many imported cases in nonendemic areas. Given recent epidemiological shifts and advances in diagnosis and treatment, a new focus on neurocysticercosis is required.

Recent findings: While South & Central America remain endemic, sub-Saharan Africa has emerged as a newly recognized hotspot. Recent developments include the potential for antigen-based assays to facilitate 'point of care' diagnosis and treatment monitoring, the combination of antiparasitic regimens, and a newer antiparasitic agent, oxfendazole, currently in clinical trial.

Summary: Recent developments offer significant hope. Wider access to neuroimaging, improved serological tests including antigen assays, and novel therapeutic strategies such as combination antiparasitic treatment have improved outcomes. Ultimately, however, a concerted prevention strategy incorporating diverse approaches will be crucial in reducing the global burden of neurological disorders associated with neurocysticercosis.

Purpose of review: Syphilis continues to be a major global health problem. In recent years epidemics of syphilis have also been reported in many high-income countries. In this review, we aim to highlight varied presentations, including recent guidelines on diagnosis and treatment, including in people with HIV (PWH).

Recent findings: Neurosyphilis is increasingly being diagnosed and presentations are varied in both the immunocompetent and immunocompromised host. An appropriate history, examination and diagnostic work-up is central to identification of neurosyphilis and to enable appropriate treatment. Clear criteria for indication and interpretation of results from lumbar punctures, neuroimaging and treatment protocols have been outlined by the British association for sexual health and HIV (BASHH) in 2024.

Summary: The increase in overall cases of syphilis has been accompanied by increases in the number of cases with neurological involvement. The presentation of neurosyphilis is variable and may occur early or late in the disease course. It is important to be aware of the varied presentations, diagnostic and treatment criteria to limit the late sequelae of disease and address the global health challenge it poses and measures being taken to help reduce this global burden.

Purpose of review: The outcome of central nervous system (CNS) tuberculosis has shown little improvement over several decades, with diagnosis remaining unconfirmed in nearly half of the cases. This review highlights current insights and advancements in the diagnosis and treatment of CNS tuberculosis.

Recent findings: Miliary pulmonary tuberculosis is often linked to CNS tuberculosis and is associated with a worse prognosis. Complications, such as, optochiasmatic arachnoiditis, strokes, and transverse myelitis severely affect prognosis and quality of life. Nearly half of tuberculous meningitis patients exhibited impaired cognition. Diagnosing CNS tuberculosis is challenging because of the low accuracy of standard tests. Advanced techniques like metagenomic and nanopore sequencing enhance detection but are hindered by high costs and limited access. Treatment outcomes remain suboptimal but approaches such as higher drug doses, novel medications, and host-directed therapies are being explored. Drug-resistant tuberculous meningitis is increasingly recognized, posing significant challenges to both diagnosis and treatment. Artificial intelligence (AI) enhances care by enabling early diagnosis, disease monitoring, and personalized treatments, improving outcomes.

Summary: CNS tuberculosis diagnosis faces challenges due to limited sensitivity and delayed results of available tests. Treatments remain suboptimal, with multidrug-resistant cases posing high mortality risks. AI aids in early diagnosis and personalized care.

Purpose of review: Gamma oscillations (30-80 Hz) play a crucial role in sensory processing and cognitive functions, with disruptions in these rhythms linked to neurological disorders such as schizophrenia and Alzheimer's disease. This review highlights the emerging role of astrocytes in regulating gamma oscillations, emphasizing their contribution to the inhibitory tone and extracellular ion homeostasis.

Recent findings: Recent studies suggest that astrocytes facilitate gamma synchrony, while dysfunction in astrocytic activity - such as impaired Ca 2+ signaling - is associated with deficits in gamma oscillations and increased network hyperexcitability. Thus, astrocytic dysfunction may contribute to the pathophysiology of gamma-related disorders.

Summary: By examining the role of astrocytes in maintaining neuronal network stability, this review highlights new aspects of neuroglia signaling.

Purpose of review: The number of known genetic movement disorders and potential treatments for these disorders have grown rapidly over the last few decades. Despite this, genetic testing for movement disorders remains relatively underutilized in clinical practice. In this review, we explore a number of barriers that prevent more routine and widespread use of genetic testing for movement disorders.

Recent findings: Cost and limited health insurance coverage as well as difficulty accessing genetic testing and counselling are major barriers to genetic testing and disproportionately affect low- and middle-income countries and specific sociodemographic groups. Clinician misperceptions and limited knowledge about genetic testing for movements disorders as well as patient and clinician concerns about the potential for genetic discrimination are further obstacles. Despite these barriers, several recent international collaborative studies have demonstrated the feasibility of delivering clinical genetic testing and genetic counselling for movement disorders on a large scale.

Summary: Concerted action at multiple organizational levels (government, specialty societies, health insurance organizations, etc.) is required in order to address the identified barriers and improve utilization of genetic testing in movement disorders on a global scale.

Purpose of review: Monitoring of disease activity and treatment response in multiple sclerosis (MS) currently relies on the integration of qualitative clinical and radiological data that is of limited predictive value. An array of quantitative digital and fluid biomarkers, many on the cusp of broad clinical translation, is expected to herald a new era of data-driven therapeutic strategy, particularly with respect to the sequencing of disease-modifying therapies (DMTs). Available highly-effective DMTs, which largely abolish acute inflammatory activity in early, relapsing MS, have a limited impact on progressive MS disease biology. However, robust digital and fluid biomarkers of progression independent of relapse activity (PIRA) have emerged as a major unmet need, fuelled by the imminent availability of treatments that target pathomechanisms such as chronic active or smouldering brain inflammation.

Recent findings: The criteria for MS diagnosis incorporate both imaging and cerebrospinal fluid (CSF) biomarkers of the disease, which lacks a single diagnostic 'test'. The recent validation of objective and quantitative CSF biomarkers, such as the k-FLC index, promises to improve diagnostic accuracy, particularly in patients with atypical or minor imaging changes. Precision monitoring of disease and is response to therapy is being transformed by the advent of clinically integrated, quantitative digital imaging tools; digital wearables and patient reported outcomes, including cognitive batteries delivered on personal devices; and an array of ultra-sensitive, readily-obtained serum fluid biomarkers that indicate the severity of tissue injury in MS. The promise of data-driven therapeutic strategy is being further explored in multimodal digital/fluid and digital twin biomarker studies that incorporate predictive artificial intelligence algorithms.

Summary: Here, we review the key near-term biomarkers that will guide individualised therapy for people with MS, targeting no evidence of disease activity (NEDA) in both early relapsing and established disease. In the medium term, composite digital and fluid biomarkers, integrated with clinical outcomes and underpinned by predictive artificial intelligence will have a transformative effect on the management of MS.

Purpose of review: Neuropathological studies in human brain tissue are indispensable for our understanding of disease mechanisms in multiple sclerosis (MS). They inform concepts of lesion evolution, tissue regeneration and disease progression, and ideally reveal new disease mechanisms and therapeutic targets. Here we review recent neuropathological studies that have advanced our knowledge of MS pathogenesis.

Recent findings: Recent cohort studies support the notion that different clinical MS disease phenotypes share underlying pathological features, and that clinical and pathological heterogeneity is derived from a variable combination of innate and adaptive inflammation, demyelinating activity, and neuroaxonal loss. Importantly, emerging technologies for spatial transcriptome analysis enable an unprecedented glimpse into the cellular composition and molecular mechanisms involved in lesion evolution. These promising technologies will help identify the identification of molecular hubs governing tissue damage and regeneration.

Summary: Recent neuropathological studies helped to identify tissue correlates of disability and disease progression. Substantial progress in molecular brain tissue analysis revealed the complexity of MS-related tissue features. Close collaboration between tissue-based, molecular, bioinformatic, pharmacologic, imaging and clinical experts is needed to continue to advance the field, particularly for the benefit of people with progressive MS.

Purpose of review: The purpose of this article is to provide an overview of progression in multiple sclerosis (MS), including definitions, pathological mechanisms, and evidence that progressive biology begins early in the disease course.

Recent findings: Definitions of MS clinical course have been refined to acknowledge the presence of both relapse and progression biology throughout the disease. Progression independent of relapse activity represents a significant proportion of disability worsening in relapsing-remitting MS (RRMS) disease. Progression in MS appears to be caused by the complex interplay of multiple processes, including nonresolving inflammation, microglial activation, oxidative stress, mitochondrial dysfunction, energetic failure, and neuro-axonal degeneration. These processes appear to begin in the earliest disease stages and their contribution to clinical phenotypes is dynamic over time. Promising results from clinical trials of tolebrutinib, in particular, underline the utility of targeting both innate and adaptive immune mechanisms to reduce disability accumulation.

Summary: Pathological processes that underpin MS progression are detectable early in RRMS, evolve throughout the disease course and correlate with disability accumulation. Progression in MS should not be defined dichotomously - the focus instead should be on recognizing progressive components based on clinical measures and biomarkers early in the disease to better individualize treatment strategies.