The Diagnostic Value of Confocal Laser Endomicroscopy in Brain Tumours When Performed by Blinded, Untrained Neuropathologists

非专业、未经培训的神经病理医师进行共聚焦激光内镜显微检查对脑肿瘤的诊断价值

Achieving maximal and safe tumour resection is a key goal in brain tumour surgery. Confocal laser endomicroscopy (CLE) enables real-time visualisation of the tissue microstructure at a cellular level, potentially helping neurosurgeons distinguish non-neoplastic from neoplastic tissue. The core aim of this study was to determine the baseline diagnostic accuracy that can be achieved with CLE alone, when assessed by neuropathologists without prior CLE training and without any additional clinical or contextual information, and to compare these findings to standard haematoxylin and eosin (H & E)-based histology in a blinded setting. CLE shows potential to distinguish between neoplastic and non-neoplastic tissue, but diagnostic accuracy remains lower than with H & E-stained slides. Training in CLE image interpretation is recommended to improve diagnostic accuracy. CLE imaging may have the potential to become a valuable tool for delineating brain tumour borders.

实现最大程度且安全的肿瘤切除是脑肿瘤手术的关键目标。共聚焦激光内镜显微镜检查（CLE）能够在细胞水平实时可视化组织微观结构，有可能帮助神经外科医生区分肿瘤组织和非肿瘤组织。本研究的核心目的是确定在没有接受过CLE培训的神经病理学家在没有任何额外临床或背景信息的情况下，仅使用CLE所能达到的基线诊断准确性，并在盲法设置下将这些结果与基于标准苏木精 - 伊红（H & E）染色的组织学结果进行比较。CLE显示出区分肿瘤组织和非肿瘤组织的潜力，但诊断准确性仍低于H & E染色切片。建议进行CLE图像解读培训以提高诊断准确性。CLE成像有可能成为界定脑肿瘤边界的有价值工具。

REF: Iff I, Gutt-Will M, Maragkou T, et al. The Diagnostic Value of Confocal Laser Endomicroscopy in Brain Tumours When Performed by Blinded, Untrained Neuropathologists. Neuropathol Appl Neurobiol. 2026;52(1):e70049. doi:10.1111/nan.70049 PMID: 41545022

G Protein-Coupled Receptor 32 Contributes to Inflammation Resolution and Neuronal Excitability Dysfunction in Patients With Focal Cortical Dysplasia IIb and Tuberous Sclerosis Complex

G蛋白偶联受体32参与局灶性皮质发育不良IIb型和结节性硬化症患者的炎症消退和神经元兴奋性功能障碍

Focal cortical dysplasia IIb (FCDIIb) and tuberous sclerosis complex (TSC) show persistent neuroinflammation that promotes epileptogenesis and epilepsy progression, suggesting that endogenous resolution of inflammation is inadequate to relieve neuronal network hyperexcitability. G-protein-coupled receptor 32 (GPR32) is a key regulator of inflammation resolution and we aimed to explore the roles of GPR32 in cortical lesions of patients with FCDIIb and TSC. Our results suggest that GPR32 may help control epilepsy in patients with FCDIIb and TSC.

IIb型局灶性皮质发育不良（FCDIIb）和结节性硬化症（TSC）表现出持续的神经炎症，这种炎症会促进癫痫发生和癫痫进展，这表明内源性炎症消退机制不足以缓解神经元网络的过度兴奋。G蛋白偶联受体32（GPR32）是炎症消退的关键调节因子，我们旨在探讨GPR32在FCDIIb和TSC患者皮质病变中的作用。我们的研究结果表明，GPR32可能有助于控制FCDIIb和TSC患者的癫痫发作。

REF: Huang K, Li J, He Z, et al. G Protein-Coupled Receptor 32 Contributes to Inflammation Resolution and Neuronal Excitability Dysfunction in Patients With Focal Cortical Dysplasia IIb and Tuberous Sclerosis Complex. Neuropathol Appl Neurobiol. 2026;52(1):e70062. doi:10.1111/nan.70062 PMID: 41582432

Enhancing the Performance of a Blood-Based Diagnostic Screening Tool for Dysferlinopathy: Optimising an Immunoassay Across Continents

提高基于血液的肌营养不良蛋白病诊断筛查工具的性能：在各大洲优化免疫测定法

Dysferlin, a 237-kDa protein crucial for muscle function, is deficient in dysferlinopathy, a rare form of muscular dystrophy caused by recessive mutations in the DYSF gene. While genetic analysis is the primary diagnostic approach, protein-based studies remain essential for confirming pathogenicity, particularly for variants of uncertain significance. This study aims to validate an immunohistochemical assay for dysferlin detection in neutrophils from peripheral blood films (PBF) and to evaluate how different storage conditions affect its performance, with particular focus on refining variables that may affect assay reliability and reproducibility. The PBF-based dysferlin assay is a rapid, cost-effective and minimally invasive screening tool, well-suited for use in resource-limited settings. It provides a viable approach for initial screening and variant assessment. As the assay's reliability is influenced by sample quality and storage conditions, proper training in collection techniques and strict adherence to storage protocols are essential for ensuring diagnostic accuracy and enabling broader clinical application.

肌营养不良蛋白（Dysferlin）是一种对肌肉功能至关重要的237 kDa蛋白质，在肌营养不良蛋白病中存在缺陷，这是一种由DYSF基因隐性突变引起的罕见肌营养不良症。虽然基因分析是主要的诊断方法，但基于蛋白质的研究对于确认致病性仍然至关重要，特别是对于意义不明确的变异。本研究旨在验证一种用于检测外周血涂片（PBF）中性粒细胞中肌营养不良蛋白的免疫组织化学检测方法，并评估不同储存条件对其性能的影响，尤其着重于优化可能影响检测可靠性和可重复性的变量。基于PBF的肌营养不良蛋白检测是一种快速、经济且微创的筛查工具，非常适合在资源有限的环境中使用。它为初步筛查和变异评估提供了一种可行的方法。由于该检测的可靠性受样本质量和储存条件的影响，因此对采集技术进行适当培训并严格遵守储存方案对于确保诊断准确性和实现更广泛的临床应用至关重要。

REF: D'Este G, Cox D, Maistrello L, et al. Enhancing the Performance of a Blood-Based Diagnostic Screening Tool for Dysferlinopathy: Optimising an Immunoassay Across Continents. Neuropathol Appl Neurobiol. 2026;52(1):e70060. doi:10.1111/nan.70060 PMID: 41605519

Truncating GAS6 Variant Disrupts Neuroglial Homeostasis in a Childhood-Onset Demyelinating Disorder

截短型GAS6变异体破坏儿童起病型脱髓鞘疾病中的神经胶质稳态

Growth arrest-specific 6 (GAS6) protein is required for cell survival through its role in TAM receptor signalling. Here, we investigate a novel autosomal recessive demyelinating disorder in a 9-year-old male presenting with progressive motor dysfunction, spasticity, seizures and cognitive decline. MRI revealed multifocal T2/FLAIR hyperintensities in periventricular, juxtacortical and brainstem white matter regions. Exome sequencing uncovered a homozygous stop-gain variant in GAS6 (c.444G>A; p.Trp148Ter). The variant results in nonsense-mediated decay and loss of protein expression and secretion. Functional assays in patient fibroblasts and HOG oligodendrocytes showed downregulation of neurotrophic and myelin-related genes (NTRK2, CNTF, EGR1, MBP, PLP), defective oligodendrocyte-process formation and increased G0/G1cell cycle arrest. Rescue experiments confirmed that wild-type GAS6, but not the truncated variant, restored cellular function. These findings establish GAS6 as a critical regulator of neuro-glial homeostasis and identify its deficiency as the cause of a previously unreported childhood-onset demyelinating disease.

生长停滞特异性蛋白6（GAS6）通过在TAM受体信号传导中的作用，对细胞存活至关重要。在此，我们研究了一名9岁男性患者所患的一种新型常染色体隐性脱髓鞘疾病，该患者表现为进行性运动功能障碍、痉挛、癫痫发作和认知能力下降。磁共振成像（MRI）显示，脑室周围、皮质下和脑干白质区域存在多灶性T2/液体衰减反转恢复（FLAIR）高信号影。外显子组测序发现GAS6基因存在纯合无义变异（c.444G>A；p.Trp148Ter）。该变异导致无义介导的mRNA降解以及蛋白表达和分泌缺失。对患者成纤维细胞和人少突胶质前体细胞（HOG）进行的功能检测显示，神经营养和髓鞘相关基因（NTRK2、CNTF、EGR1、MBP、PLP）表达下调，少突胶质细胞突起形成缺陷，且细胞周期停滞于G0/G1期的比例增加。拯救实验证实，野生型GAS6而非截短变异型GAS6能够恢复细胞功能。这些发现表明GAS6是神经胶质稳态的关键调节因子，并确定其缺乏是一种此前未报道的儿童期起病脱髓鞘疾病的病因。

REF: Diksha, Kumar A, Gaurav V, Mathuria YP, Gupta SK, Ghosh DK. Truncating GAS6 Variant Disrupts Neuroglial Homeostasis in a Childhood-Onset Demyelinating Disorder. Neuropathol Appl Neurobiol. 2026;52(1):e70063. doi:10.1111/nan.70063 PMID: 41612647

Cortical Layer-Specific Remodelling of Parvalbumin and Perineuronal Net Networks in Alcohol Use Disorder

酒精使用障碍中小白蛋白和神经周围网络的皮质层特异性重塑

Alcohol use disorder (AUD) is a chronically relapsing condition marked by a pathological shift in behaviour, where excessive motivational drive predominates over cognitive control. Brodmann area 6 (BA6) is a key cortical region that integrates cognitive control with motor output and striatal circuits. Cellular alterations in the BA6 can shift from flexible, goal-directed planning to habitual, compulsive behaviours. This study reveals layer-specific remodelling of PNN and PV networks in the human cortex in AUD cases, suggesting shifts in AUD behaviours are potentially attributed to PV neuronal activity regulated by PNN in specific cortical layers. Together, this study identifies AUD-related neuropathology and provides insight into the mechanisms underlying persistent alcohol-seeking behaviour.

酒精使用障碍（AUD）是一种慢性复发性疾病，其特征是行为发生病理性改变，过度的动机驱动压倒了认知控制。布罗德曼6区（BA6）是一个关键的皮质区域，它将认知控制与运动输出和纹状体回路相整合。BA6中的细胞改变可使行为从灵活的、目标导向的规划转变为习惯性的、强迫性的行为。这项研究揭示了AUD患者大脑皮质中围神经元网（PNN）和生长抑素阳性中间神经元（PV）网络的层特异性重塑，表明AUD行为的改变可能归因于特定皮质层中由PNN调节的PV神经元活动。总之，这项研究确定了与AUD相关的神经病理学特征，并为持续的觅酒行为背后的机制提供了见解。

REF: Karas T, Prasad AA. Cortical Layer-Specific Remodelling of Parvalbumin and Perineuronal Net Networks in Alcohol Use Disorder. Neuropathol Appl Neurobiol. 2026;52(1):e70066. doi:10.1111/nan.70066 PMID: 41638216

Evaluating Basigin as a Potential Biomarker of Blood–Brain Barrier Dysfunction in Cerebral Amyloid Angiopathy

评估基底膜蛋白作为脑淀粉样血管病血脑屏障功能障碍潜在生物标志物的研究

Blood-brain barrier (BBB) dysfunction may be involved in the pathophysiology of neurodegenerative disorders, including sporadic cerebral amyloid angiopathy (CAA). Because basigin (BSG) may induce activity of matrix metalloproteinases and thereby BBB breakdown, we investigated BSG expression in CAA brain tissue with immunohistochemistry and as cerebrospinal fluid biomarker for BBB dysfunction in patients with CAA. CSF concentrations of BSG may be related to altered expression at the BBB; the BSG concentrations in CSF may thus serve as a biomarker of BBB function, although a contribution of choroid plexus epithelial BSG cannot be entirely excluded. Independent cohorts are needed to replicate these observations before we can conclude that reduced CSF concentrations of BSG may indicate an alteration of the BBB in patients with CAA.

血脑屏障（BBB）功能障碍可能参与神经退行性疾病的病理生理过程，包括散发性脑淀粉样血管病（CAA）。由于基底膜蛋白（BSG）可能诱导基质金属蛋白酶的活性，从而导致血脑屏障破坏，我们通过免疫组织化学方法研究了CAA脑组织中BSG的表达情况，并将其作为CAA患者血脑屏障功能障碍的脑脊液生物标志物进行研究。脑脊液中BSG的浓度可能与血脑屏障处的表达改变有关；因此，脑脊液中BSG的浓度可作为血脑屏障功能的生物标志物，尽管不能完全排除脉络丛上皮BSG的影响。在我们得出CAA患者脑脊液中BSG浓度降低可能提示血脑屏障改变这一结论之前，需要独立队列来重复这些观察结果。

REF: Stellingwerf A, Bosveld D, Jäkel L, et al. Evaluating Basigin as a Potential Biomarker of Blood-Brain Barrier Dysfunction in Cerebral Amyloid Angiopathy. Neuropathol Appl Neurobiol. 2026;52(1):e70064. doi:10.1111/nan.70064 PMID: 41708154