Mechanisms of COVID-19-associated olfactory dysfunction

COVID-19-associated嗅觉障碍的机制

This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations, and current understanding of the mechanisms of COVID-19-associated olfactory dysfunction. The pathogenic mechanisms underlying COVID-19-associated olfactory dysfunction are complex and likely multifactorial. Infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, whereas olfactory receptor neuron dysfunction, olfactory bulb injury, and alterations in the olfactory cortex may lead to persistent, long-term olfactory dysfunction.

本文旨在对COVID-19-associated嗅觉障碍的流行病学，临床表现和目前对其机制的理解进行全面总结。COVID-19-associated嗅觉功能障碍的致病机制是复杂的，可能是多因素的。sustentacular细胞的感染和相关的粘膜炎症可能是急性，短暂的嗅觉丧失的罪魁祸首，而嗅觉受体神经元功能障碍，嗅球损伤和嗅觉皮层的改变可能导致持续的，长期的嗅觉功能障碍。

REF: Chang K, Zaikos T, Kilner-Pontone N, Ho CY. Mechanisms of COVID-19-associated olfactory dysfunction. Neuropathol Appl Neurobiol. 2024;50(2):e12960. doi:10.1111/nan.12960 PMID: 38419211 PMCID: PMC10906737

Cerebellar phenotypes in germline PTEN mutation carriers

生殖系PTEN突变携带者的小脑表型

PTEN hamartoma tumour syndrome (PHTS), due to an inherited PTEN pathogenetic variant, is characterised by macrocephaly, multiple hamartomas and an increased risk of cancer. In this review, we focused on the different phenotypes that involve the cerebellum in PHTS patients. Specifically, dysplastic gangliocytoma of the cerebellum, also known as Lhermitte–Duclos disease, is a pathognomonic finding of PHTS, and autism spectrum disorders affect young patients. Furthermore, we reviewed pathological changes induced by cerebellar PTEN loss in both humans and animal models.

由于遗传性PTEN致病变异，PTEN错构瘤肿瘤综合征 (PHTS) 的特征是大头畸形，多发性错构瘤和癌症风险增加。在这篇综述中，我们重点研究了PHTS患者小脑的不同表型。具体来说，小脑发育不良性神经节细胞瘤，也称为lhermitte-duclos病，是PHTS的病原学发现，自闭症谱系障碍影响年轻患者。此外，我们回顾了人类和动物模型中小脑PTEN丢失引起的病理变化。

REF: Gambini D, Ferrero S, Bulfamante G, Pisani L, Corbo M, Kuhn E. Cerebellar phenotypes in germline PTEN mutation carriers. Neuropathol Appl Neurobiol. 2024;50(2):e12970. doi:10.1111/nan.12970 PMID: 38504418

Adult brain tumour research in 2024: Status, challenges and recommendations

2024年成人脑肿瘤研究: 现状、挑战与建议

Brain cancer survival rates are among the lowest of all cancers, with very little improvement having been achieved over the past two decades. In this position paper, a multidisciplinary group of brain tumour experts has investigated the current neuro-oncology research landscape in the United Kingdom to highlight challenges and make UK-specific recommendations on how to address them. The findings are structured around seven key priorities and three cross-cutting themes, pertinent to global neuro-oncology research but described in the specific context of the United Kingdom.

脑癌存活率是所有癌症中最低的，在过去的二十年中几乎没有改善。在本立场文件中，一个由脑肿瘤专家组成的多学科小组调查了英国当前的神经肿瘤学研究领域，以突出挑战并就如何解决这些挑战提出针对英国的建议。研究结果围绕七个关键优先事项和三个交叉主题展开，这些主题与全球神经肿瘤学研究有关，但在英国的特定背景下进行了描述。

REF: Purshouse K, Bulbeck HJ, Rooney AG, et al. Adult brain tumour research in 2024: Status, challenges and recommendations. Neuropathol Appl Neurobiol. 2024;50(2):e12979. doi:10.1111/nan.12979 PMID: 38605644

Regulation of CNS pathology by Serpina3n/SERPINA3: The knowns and the puzzles

Serpina3n/SERPINA3对CNS病理的调节: 已知和困惑

The immune-related molecule Serpina3n/SERPINA3 is dysregulated in people affected by system inflammation, normal ageing, Alzheimer's disease, multiple sclerosis and CNS trauma. Recent preclinical data increasingly indicate the importance of Serpina3n/SERPINA3 in neuropathology. The ‘good’ or ‘bad’ aspects of Serpina3n/SERPINA3-related pathology are hypothesised to depend on the cellular sources and/or disease/injury types. Therefore, tissue or cell-specific tools are necessary to decipher its roles in different CNS disease models.

免疫相关分子Serpina3n/SERPINA3在受系统炎症，正常衰老，阿尔茨海默氏病，多发性硬化症和CNS创伤影响的人群中失调。最近的临床前数据越来越多地表明Serpina3n/SERPINA3在神经病理学中的重要性。假设Serpina3n/SERPINA3-related病理学的 “好” 或 “坏” 方面取决于细胞来源和/或疾病/损伤类型。因此，组织或细胞特异性工具对于破译其在不同CNS疾病模型中的作用是必要的。

REF: Zhu M, Lan Z, Park J, Gong S, Wang Y, Guo F. Regulation of CNS pathology by Serpina3n/SERPINA3: The knowns and the puzzles. Neuropathol Appl Neurobiol. 2024;50(2):e12980. doi:10.1111/nan.12980 PMID: 38647003

Automated whole slide morphometry of sural nerve biopsy using machine learning

使用机器学习的腓肠神经活检的自动全载玻片形态测量

A machine learning-based application automatically performs morphometric and spatial analyses with whole slide images of biopsied sural nerves.

基于机器学习的应用程序会自动对活检的腓肠神经的整个幻灯片图像进行形态测量和空间分析。

REF: Ono D, Kawai H, Kuwahara H, Yokota T. Automated whole slide morphometry of sural nerve biopsy using machine learning. Neuropathol Appl Neurobiol. 2024;50(2):e12967. doi:10.1111/nan.12967 PMID: 38448224

Chronic traumatic encephalopathy neuropathologic change in former Australian rugby players

前澳大利亚橄榄球运动员的慢性创伤性脑病神经病理变化

In this clinicopathological case series of former Australian rugby code players, four of six had post mortem CTE-NC. All met current diagnostic criteria for TES and had multiple pathologies at post mortem. Future studies are needed to improve the specificity of the TES consensus diagnostic criteria for predicting the presence of CTE-NC, and we encourage future researchers to report all neuropathological comorbidities clearly in their clinicopathological studies.

在这个前澳大利亚橄榄球代码运动员的临床病理病例系列中，六分之四的尸体具有死后cte-nc。所有患者均符合当前的TES诊断标准，并在死后具有多种病理。未来的研究需要提高预测cte-nc存在的TES共识诊断标准的特异性，我们鼓励未来的研究人员在其临床病理研究中清楚地报告所有神经病理合并症。

REF: Shepherd CE, McCann H, McLean CA, Iverson GL, Gardner AJ. Chronic traumatic encephalopathy neuropathologic change in former Australian rugby players. Neuropathol Appl Neurobiol. 2024;50(2):e12972. doi:10.1111/nan.12972 PMID: 38502287

Targeting the EGFR pathway: An alternative strategy for the treatment of tuberous sclerosis complex?

靶向EGFR通路: 治疗结节性硬化症的替代策略？

Epilepsy-surgery specimens from TSC as well as FCD2B brain lesions showed an overexpression of EGFR. Interestingly, when primary patient-derived cells from tuber, SEGA or FCD2B were treated with the EGFR inhibitor afatinib, a decrease in cell viability and proliferation was observed.

癫痫-来自TSC以及FCD2B脑损伤的手术标本显示EGFR的过度表达。有趣的是，当用EGFR抑制剂阿法替尼处理来自块茎、SEGA或FCD2B的原代患者来源的细胞时，观察到细胞活力和增殖的降低。

REF: Schachenhofer J, Gruber VE, Fehrer SV, et al. Targeting the EGFR pathway: An alternative strategy for the treatment of tuberous sclerosis complex?. Neuropathol Appl Neurobiol. 2024;50(2):e12974. doi:10.1111/nan.12974 PMID: 38562027

Revisiting the relevance of Hirano bodies in neurodegenerative diseases

重新审视平野体在神经退行性疾病中的相关性

Hirano bodies (HBs) in the posterior hippocampus were systematically evaluated in a cohort of 193 patients with major neurodegenerative diseases, including Alzheimer's disease, Lewy body disease and progressive supranuclear palsy. Three morphological types of HBs were identified in the CA1: classic rod-shaped HB (CHB), balloon-shaped HB (BHB) and string-shaped HB (SHB), the latter being newly discovered. The prevalence of each HB type differed among disease groups, indicating associations between HB and various neurodegenerative diseases, with distinct morphological types evident across pathologies.

在一组193名患有主要神经退行性疾病的患者中，系统地评估了海马后部的平野体 (HBs)，包括阿尔茨海默氏病，路易体病和进行性核上性麻痹。在CA1中鉴定出三种形态类型的HBs: 经典的杆状HB (CHB)，气球状HB (BHB) 和弦状HB (SHB)，后者是新发现的。每种HB类型的患病率在疾病组之间有所不同，表明HB与各种神经退行性疾病之间存在关联，并且在各种病理之间具有明显的形态类型。

REF: Yoshida K, Forrest SL, Ichimata S, et al. Revisiting the relevance of Hirano bodies in neurodegenerative diseases. Neuropathol Appl Neurobiol. 2024;50(2):e12978. doi:10.1111/nan.12978 PMID: 38634242