Developmental Cognitive Neurosciences Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
Brain. 2012 Oct;135(Pt 10):3153-64. doi: 10.1093/brain/aws213. Epub 2012 Sep 3.
Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal injury may be evident in human children after prolonged febrile seizures. The current study addressed this question by investigating memory abilities in 26 children soon after a prolonged febrile seizure (median: 37.5 days) and compared their results to those of 37 normally developing children. Fifteen patients were reassessed at a mean of 12.5 months after their first assessment to determine the transiency of any observed effects. We used the visual paired comparison task to test memory abilities in our group, as this task does not depend on verbal abilities and also because successful performance on the task has been proven to depend on the presence of functional hippocampi. Our findings show that patients perform as well as controls in the absence of a delay between the learning phase and the memory test, suggesting that both groups are able to form representations of the presented stimulus. However, after a 5-min delay, patients' recognition memory is not different from chance, and comparison of patients and controls points to an accelerated forgetting rate in the prolonged febrile seizure group. The patients' performance was not related to the time elapsed from the acute event or the duration of the prolonged febrile seizure, suggesting that the observed effect is not a by-product of the seizure itself or a delayed effect of medication administered to terminate the seizure. By contrast, performance was related to hippocampal size; participants with the smallest mean hippocampal volumes revealed the biggest drop in performance from the immediate to the delayed paradigm. At follow-up, children were still showing deficiencies in recognizing a face after a 5-min delay. Similarly, this suggests that the observed memory impairments are not a transient effect of the prolonged febrile seizures. This is the first report of such impairments in humans, and it is clinically significant given the links between mesial temporal sclerosis and prolonged febrile seizures. The persistence of these impairments a year onwards signals the potential benefits of intervention in these children who run the risk of developing episodic memory deficits in later childhood.
患有长时间热性惊厥史的儿童在磁共振成像上显示出急性海马损伤的迹象。此外,动物研究表明,在发育过程中患有热性惊厥的成年大鼠表现出记忆障碍。这些证据表明,与海马损伤相关的记忆障碍可能在长时间热性惊厥后的人类儿童中表现出来。本研究通过调查 26 名儿童在长时间热性惊厥后不久(中位数:37.5 天)的记忆能力,并将其结果与 37 名正常发育的儿童进行比较,来解决这个问题。15 名患者在第一次评估后平均 12.5 个月进行重新评估,以确定任何观察到的影响的短暂性。我们使用视觉配对比较任务来测试我们组的记忆能力,因为该任务不依赖于语言能力,并且因为已经证明成功完成任务依赖于功能性海马的存在。我们的研究结果表明,在学习阶段和记忆测试之间没有延迟的情况下,患者的表现与对照组一样好,这表明两组都能够对呈现的刺激形成表示。然而,在 5 分钟的延迟后,患者的识别记忆与机会没有区别,并且患者和对照组的比较表明,在长时间热性惊厥组中,遗忘率加快。患者的表现与从急性事件到发作的时间或长时间热性惊厥的持续时间无关,这表明观察到的影响不是发作本身的副产物或终止发作的药物的延迟作用。相比之下,表现与海马体大小有关;海马体平均体积最小的参与者表现出从即时到延迟范式的最大性能下降。在随访中,即使在 5 分钟的延迟后,儿童仍在识别面孔方面存在缺陷。同样,这表明观察到的记忆障碍不是长时间热性惊厥的短暂影响。这是在人类中首次报道此类损伤,并且鉴于内侧颞叶硬化症与长时间热性惊厥之间的联系,这在临床上具有重要意义。这些损伤在一年后仍然存在,这表明对这些有发展为后期儿童期发作性记忆缺陷风险的儿童进行干预具有潜在益处。