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结核性脑膜炎的流行病学、发病机制、临床表现及治疗策略

Epidemiology, Pathogenesis, Clinical Manifestations, and Management Strategies of Tuberculous Meningitis.

作者信息

Oo Nicholas, Agrawal Devendra K

机构信息

Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766 USA.

出版信息

Arch Intern Med Res. 2025;8(1):48-58. doi: 10.26502/aimr.0195. Epub 2025 Feb 10.

Abstract

Tuberculous meningitis (TBM), the most severe manifestation of extrapulmonary tuberculosis, poses significant global health challenges due to its high mortality rates and complex pathophysiology. This review synthesizes recent findings on TBM, covering epidemiology, pathogenesis, clinical manifestations, diagnostics, and management strategies. TBM disproportionately affects immunocompromised populations, including individuals with HIV, with the highest mortality observed in low-resource settings. Pathogenesis involves Mycobacterium tuberculosis breaching the blood-brain barrier, eliciting a granulomatous inflammatory response that contributes to neurotoxicity. Advances in diagnostics, such as next-generation sequencing and novel imaging techniques, have improved early detection and treatment guidance. Management strategies emphasize multidrug regimens, adjunctive corticosteroids, and emerging therapies like intrathecal administration and nanoparticle-based drug delivery. Host-directed therapies targeting immune modulation and oxidative stress show promise in improving outcomes, particularly for drug-resistant TBM. Despite advancements, diagnostic delays, treatment resistance, and high rates of neurological effects underscore the need for further research. Preventive strategies focusing on early diagnosis, modifiable risk factor management, and public health interventions are critical to reducing global burden of TBM. This review highlights the importance of integrating innovative diagnostics, tailored treatments, and preventive measures to address the challenges of TBM and improve patient outcomes.

摘要

结核性脑膜炎(TBM)是肺外结核病最严重的表现形式,因其高死亡率和复杂的病理生理学而给全球卫生带来重大挑战。本综述综合了关于TBM的最新研究结果,涵盖流行病学、发病机制、临床表现、诊断和管理策略。TBM对免疫功能低下人群的影响尤为严重,包括艾滋病毒感染者,在资源匮乏地区观察到的死亡率最高。发病机制涉及结核分枝杆菌突破血脑屏障,引发肉芽肿性炎症反应,进而导致神经毒性。诊断方面的进展,如下一代测序和新型成像技术,改善了早期检测和治疗指导。管理策略强调多药联合方案、辅助使用皮质类固醇,以及鞘内给药和基于纳米颗粒的药物递送等新兴疗法。针对免疫调节和氧化应激的宿主导向疗法在改善治疗效果方面显示出前景,特别是对于耐药性TBM。尽管取得了进展,但诊断延迟、治疗耐药性以及高比例的神经学影响凸显了进一步研究的必要性。侧重于早期诊断、可改变风险因素管理和公共卫生干预措施的预防策略对于减轻全球TBM负担至关重要。本综述强调了整合创新诊断方法、量身定制的治疗方案和预防措施以应对TBM挑战并改善患者治疗效果的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d26/11887623/a00d8f88bded/nihms-2058538-f0001.jpg

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