Pardo Carlos A, Nabbout Rima, Galanopoulou Aristea S
Department of Neurology, Division of Neuroimmunology and Neuroinfectious Disorders, Center for Pediatric Rasmussen Syndrome, Johns Hopkins University School of Medicine, Baltimore, MD, USA,
Neurotherapeutics. 2014 Apr;11(2):297-310. doi: 10.1007/s13311-014-0265-2.
The mechanisms of epileptogenesis in pediatric epileptic syndromes are diverse, and may involve disturbances of neurodevelopmental trajectories, synaptic homeostasis, and cortical connectivity, which may occur during brain development, early infancy, or childhood. Although genetic or structural/metabolic factors are frequently associated with age-specific epileptic syndromes, such as infantile spasms and West syndrome, other syndromes may be determined by the effect of immunopathogenic mechanisms or energy-dependent processes in response to environmental challenges, such as infections or fever in normally-developed children during early or late childhood. Immune-mediated mechanisms have been suggested in selected pediatric epileptic syndromes in which acute and rapidly progressive encephalopathies preceded by fever and/or infections, such as febrile infection-related epilepsy syndrome, or in chronic progressive encephalopathies, such as Rasmussen encephalitis. A definite involvement of adaptive and innate immune mechanisms driven by cytotoxic CD8(+) T lymphocytes and neuroglial responses has been demonstrated in Rasmussen encephalitis, although the triggering factor of these responses remains unknown. Although the beneficial response to steroids and adrenocorticotropic hormone of infantile spasms, or preceding fever or infection in FIRES, may support a potential role of neuroinflammation as pathogenic factor, no definite demonstration of such involvement has been achieved, and genetic or metabolic factors are suspected. A major challenge for the future is discovering pathogenic mechanisms and etiological factors that facilitate the introduction of novel targets for drug intervention aimed at interfering with the disease mechanisms, therefore providing putative disease-modifying treatments in these pediatric epileptic syndromes.
小儿癫痫综合征的癫痫发生机制多种多样，可能涉及神经发育轨迹、突触稳态和皮质连接的紊乱，这些紊乱可能发生在脑发育、婴儿早期或儿童期。尽管遗传或结构/代谢因素常与特定年龄的癫痫综合征相关，如婴儿痉挛症和韦斯特综合征，但其他综合征可能由免疫致病机制或能量依赖过程对环境挑战（如正常发育儿童在儿童早期或晚期的感染或发热）的反应所决定。在某些小儿癫痫综合征中已提出免疫介导机制，其中急性和快速进展性脑病先于发热和/或感染，如发热感染相关癫痫综合征，或慢性进展性脑病，如拉斯穆森脑炎。在拉斯穆森脑炎中已证实细胞毒性CD8(+) T淋巴细胞和神经胶质反应驱动的适应性和先天性免疫机制有明确参与，尽管这些反应的触发因素仍不清楚。尽管婴儿痉挛症对类固醇和促肾上腺皮质激素的有益反应，或FIRES中先前的发热或感染，可能支持神经炎症作为致病因素的潜在作用，但尚未明确证实这种参与，并且怀疑有遗传或代谢因素。未来的一个主要挑战是发现致病机制和病因因素，以促进引入旨在干扰疾病机制的新型药物干预靶点，从而为这些小儿癫痫综合征提供假定的疾病修饰治疗。
