Current Opinion in Neurology最新文献

Purpose of review: Ischemic stroke remains a leading cause of death and disability worldwide, with carotid atherosclerosis as a major underlying mechanism. For decades, treatment decisions were based primarily on luminal stenosis, overlooking the biological complexity of plaque instability. This review summarizes recent progress in the imaging-based identification and risk stratification of unstable cerebrovascular plaque, emphasizing the transition from geometric to biological evaluation.

Recent findings: Advances in CT, MRI, and ultrasound have enabled in vivo visualization of key features associated with plaque vulnerability, including intraplaque hemorrhage, fibrous cap rupture, neovascularization, inflammation, and perivascular fat alterations. Dual-energy and photon-counting CT now provide spectral and spatial information capable of tissue differentiation at submillimeter scales. MRI offers superior soft-tissue characterization, while contrast-enhanced ultrasound reveals microvascular activity and flow dynamics. The recent introduction of standardized interpretative systems, such as Plaque-reporting and data system (RADS), allows integration of multimodal findings into a unified risk framework.

Summary: Contemporary imaging has transformed the assessment of carotid atherosclerosis from a static measurement of stenosis into a dynamic, biology-driven discipline. The combination of advanced imaging, quantitative analysis, and emerging molecular and genetic correlates promises to refine individualized risk prediction and guide targeted prevention strategies for cerebrovascular disease.

Purpose of review: This review highlights recent advances in neuro-vestibular rehabilitation, with emphasis on vestibular adaptation and emerging mobile technologies. It summarizes developments in promoting vestibular plasticity and discusses novel tools such as virtual reality, wearable sensors, and telehealth platforms that enhance access, engagement, and outcomes. The scope is broad, focusing on general principles rather than specific populations.

Recent findings: New methods to enhance vestibulo-ocular reflex (VOR) adaptation include incremental adaptation devices and gamified exercises. Inducing VOR gain-down adaptation temporarily increases postural sway, which normalizes via sensory reweighting, demonstrating central compensation. Portable tools like StableEyes show promise in boosting VOR gain with brief sessions. Concurrently, technology-driven approaches are gaining traction. Gamified mobile applications and wearable sensors allow home-based rehabilitation with remote supervision and monitoring, showing promising results in conditions like multiple sclerosis. Virtual reality interventions and telehealth models accelerated during the COVID-19 era, expanding therapy delivery to underserved populations. Adjunctive methods such as vibrotactile feedback and galvanic vestibular stimulation are emerging as complementary therapies.

Summary: Recent developments are advancing vestibular rehabilitation by refining adaptive training techniques and leveraging digital tools to overcome barriers in access and adherence. These innovations point to a more personalized, technology-enabled approach to optimizing neuro-vestibular recovery.

Purpose of review: Vestibular migraine (VM) is a prevalent yet underdiagnosed cause of vestibular symptoms, which overlaps with other vestibular and migraine-related conditions. This review focuses on detailed clinical phenomenology, alongside comorbidities, and the appraisal of emerging therapies.

Recent findings: Recent work shows that migraine-associated features such as allodynia, photophobia, and movement sensitivity sharpen clinical discrimination. Premonitory and cognitive symptoms, including brain fog and executive slowing, are increasingly recognized. Chronobiological factors such as menstrual cycle and menopause modulate susceptibility. Oculomotor assessment and neuroimaging point to disturbed integration across vestibular, sensorimotor, and visual networks rather than focal lesions. Comorbid persistent postural-perceptual dizziness, dysautonomia, and autoimmune tendencies complicate diagnosis and management. Early trials support calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxin-A, with lifestyle interventions, and nutraceuticals commonly being used, although clinical trial designs and endpoints remain heterogeneous.

Summary: VM reminds us that bedside examination remains the anchor: a detailed history, eye-movement examination, and context refine diagnosis. Objective markers and interdisciplinary strategies assist rather than replace clinical judgement. Further studies should integrate multimodal assessment and phenotype-guided treatment stratification.

Purpose of review: Alzheimer's disease (AD) is commonly defined by its hallmark brain pathologies, yet mounting evidence shows that metabolic impairment particularly linked to mitochondrial dysfunction, is a central and systemic feature of the disease. This review highlights consistent abnormalities in mitochondrial function, and turnover (mitophagy) across multiple AD-derived peripheral cells, including skin fibroblasts, lymphocytes, platelets, and peripheral blood mononuclear cells. We also report on potential peripheral AD biomarkers linked to mitochondria dysfunction in AD.

Recent findings: Mitochondrial abnormalities in peripheral cells from individuals with AD robustly correlate with disease development. These mitochondrial dysfunctions mostly include reduced respiratory chain activity, increased accumulation of reactive oxygen species (ROS), altered mitochondrial membrane potential, and consequently decreased ATP production. Studies have also identified a complex pattern of mitochondrial hyperactivity and hypoactivity in peripheral cells of AD patients that appears to depend on the stage of AD and whether the disease is sporadic or familial. Furthermore, multiple steps of the mitophagy pathway are disrupted in peripheral cells as AD progresses. Finally, biochemical and proteomic analyses of peripheral fluids further support the loss of mitochondrial homeostasis in AD patients.

Summary: Collectively, the reviewed findings support mitochondrial homeostasis disruption as a core pathophysiological component of AD and a promising target for biomarker development and therapeutic intervention.

Purpose of review: To review progress in developing new pharmacological treatments for epilepsy, focusing on agents in clinical development.

Recent findings: Over 30 different treatments are currently in clinical development, including novel small molecules, nucleic acid-based therapies, stem cells, microbiome-targeting bacteria, and repurposed drugs originally approved for other indications. Most of these treatments target rare epilepsies, particularly the developmental and epileptic encephalopathies, reflecting a development shift from common epilepsies to rare drug-resistant syndromes where unmet therapeutic needs are greatest. Most compounds are still in early development, and publicly accessible data consist mainly of conference reports and congress abstracts. For only two compounds (the Kv7 activator azetukalner and the inhaled emergency treatment Staccato alprazolam) has evidence of efficacy been obtained from relatively large, well designed randomized placebo-controlled trials.

Summary: New paradigms in drug discovery have brought to development innovative treatments with diverse targets and mechanisms of action. Many of these treatments are etiology-targeting and have the potential for disease-modifying effects. Although high-quality evidence is awaited, there is hope that over the next few years, much needed life-changing therapies will be widely available for millions of people with disabling, drug-resistant epilepsies.

Purpose of review: One in five patients with epilepsy has idiopathic generalized epilepsy (IGE). Novel definitions of seizure types, recent data on pharmacotherapy, and new studies on psychiatric and cognitive comorbidities will be critically discussed.

Recent findings: Epileptic seizures have been re-classified by the International League Against Epilepsy (ILAE), acknowledging absence-to-tonic-clonic seizures and generalized negative myoclonic seizures. Differing from the classical ILAE definition of IGE subtypes, current evidence underlines that IGEs represent rather a neurobiological continuum than separate syndromes. Valproate is still the most efficacious compound to suppress myoclonic and tonic-clonic seizures, but novel data confirm the high risk for both anatomical and neurodevelopmental teratogenicity. However, switching from valproate to other antiseizure medications commonly results in seizure recurrence or worsening. As compared to the general population, persons with IGE have a two- to fourfold increased risk of psychiatric disorders, the lifetime risk is 30-50%. Bidirectional associations between IGE and psychiatric conditions suggest that the latter are integral components of a broader IGE endophenotype.

Summary: Valproate continues to be the most efficacious treatment for IGE but also the most teratogenic, leaving women who plan to become pregnant in a dilemma. Psychiatric comorbidities are frequent in IGE and thus require special attention and a holistic treatment approach.

Purpose of review: To summarize recent animal, postmortem and in vivo human studies examining the role of the noradrenergic and serotonergic system in the pathophysiology and symptomatology of Alzheimer's disease (AD).

Recent findings: Early in adulthood, the locus coeruleus and raphe nucleus accumulate tau, undergo morphological changes, and exhibit hyperexcitability, which contributes to the development of neuropsychiatric symptoms. As cortical AD pathology increases, these nuclei become hypoactive, but elevated neurotransmitter levels persist in the cortex, presumably driving amyloid-related hyperexcitability and contributing to tau spreading and cognitive decline.

Summary: The pathologic changes occurring within these monoaminergic systems temporally align with the observation that neuropsychiatric symptoms precede cognitive changes in AD, indicating that these systems link the earliest pathobiology of the disease to the evolution of the symptoms. The proposed monoaminergic framework intends to guide researchers into investigating the temporal dynamics between monoaminergic changes, AD pathology, and symptoms, with the ultimate goal of evaluating and developing effective precision therapeutic approaches taking into account the disease stage and symptom profile.

Purpose of review: Patients with grade 2 and 3 meningioma have high recurrence rates and limited treatment options after failure of radiation and surgery. Recent advances in molecular profiling of these tumors have enabled the investigation of novel targeted therapeutic approaches.

Recent findings: Innovative treatment strategies under investigation for recurrent high-grade meningiomas include targeted therapies, immunotherapy, and radionuclide-based approaches. Inhibition of angiogenesis, histone deacetylases, FAK, mTOR, and CDK4/6 pathways has shown early signs of activity in small clinical trials of patients with recurrent meningiomas. Immunotherapy, such as immune checkpoint inhibition (ICI), has also demonstrated prolonged disease control in a subset of patients. Larger randomized studies are needed for further investigation of the efficacy and safety of these newer therapies in patients with high-grade and recurrent meningioma.

Summary: Emerging molecularly driven treatment strategies show promise for the treatment of patients with high-grade meningiomas. Larger trials that incorporate molecular testing are warranted to fully evaluate their therapeutic potential.

Purpose of review: Recovery after spinal cord injury (SCI) is variable, and the contribution of locomotor training to neurological and functional outcomes remains debated. This review summarizes post-SCI locomotor recovery patterns, compares training modalities, and presents recovery findings from the Kunming Locomotor Training (KLT) program, one of the largest reported series of patients with initial complete (AIS A) injuries.

Recent findings: Several months of intensive task-specific overground training yielded substantial gains in neurological, locomotor, and autonomic outcomes. In a retrospective cohort of 485 AIS A patients, 47% improved their AIS grade, while nearly all showed some locomotor recovery measured by the Kunming Locomotor Scale (KLS). A ≥4-point KLS gain strongly predicted AIS conversion (sensitivity 83%, specificity 82%). Recovery probability was highest with lower thoracic and lumbar injuries. Improvements, including ambulation with assistive devices, and significant bladder and bowel recovery occurred even without AIS change. These outcomes reinforce the importance of active, patient-driven training.

Summary: KLT experience indicates that prolonged, intensive overground locomotor training can promote neurological and functional recovery in individuals with initially complete injuries. KLS provides a sensitive measure of functional progress. These findings underscore the clinical value of task-specific stepping and provide a new benchmark for evaluating sustained rehabilitation strategies and research into post-SCI recovery.

Purpose of review: Accurate and reliable determination of tumor response and progression on neuroimaging is critical to identify effective therapies for glioma in clinical trials. In this article, we review response assessment criteria for adult glioma including their evolution over time, current recommendations, limitations, and future directions.

Recent findings: Response Assessment in Neuro-Oncology (RANO) 2.0 delineates unified magnetic resonance imaging (MRI)-based criteria informed by patient data to evaluate endpoints of tumor response and tumor progression. The positron emission tomography (PET) RANO 1.0 criteria propose endpoints for tumor progression and response on amino acid PET imaging.

Summary: The RANO 2.0 criteria provide standardized recommendations to assess tumor response and progression across adult glioma clinical trials regardless of tumor grade, contrast enhancement, molecular profile or treatment modality. Additional validation and exploratory studies can facilitate future refinements to the criteria and possible incorporation of novel neuroimaging endpoints. Advanced imaging modalities such as perfusion MRI and amino acid PET may help overcome some limitations of MRI-based response assessment.