Timing of cognitive decline in CLN3 disease
Timing of cognitive decline in CLN3 disease
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DOI：
10.1007/s10545-018-0143-x
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发表时间：
2018-03-01
影响因子：
4.2
通讯作者：
van Hasselt, Peter M.
中科院分区：
文献类型：
--
作者：
Kuper, Willemijn F. E.;van Alfen, Claudia;van Hasselt, Peter M.
背景 CLN3 疾病是儿童神经变性的主要原因。人们认为，6 岁左右出现视力障碍会先于认知能力下降几年，但谨慎的报告对这一范式提出了质疑。我们研究的目的是描绘 CLN3 疾病认知能力下降的时间。 方法 使用视觉和认知能力下降的发病年龄以及来自文献的患者描述的 IQ 分数，并补充来自回顾性转诊中心队列的 IQ 分数和学校历史，对 CLN3 疾病的早期神经认知功能进行分析。我们分别分析了长期和经典 CLN3，并添加了一组被诊断为青少年发病性黄斑变性（早发性 Stargardt 病）的患者，以控制视力快速丧失对神经认知功能可能产生的影响。 结果 认知能力下降的平均年龄为 6.8 岁（范围 2-13 岁，n = 19），而视力恶化的平均年龄为 6.4 岁（范围 4-9 岁，n = 19）。 81）这一点得到了经典 CLN3 疾病中智商分数早期下降的支持。迁延性 CLN3 患者的视力丧失的起病时间和病程相似。转诊队列中诊断时智商水平下降（平均 68.4，范围 57-79，n = 9）与 Stargardt 病患者的异常早期学校史（与正常学校史和认知形成对比）一致相关。 结论 在经典 CLN3 疾病的诊断周围普遍存在认知功能障碍。
Background CLN3 disease is a major cause of childhood neurodegeneration. Onset of visual failure around 6 years of age is thought to precede cognitive deterioration by a few years, but casuistic reports question this paradigm. The aim of our study is to delineate timing of cognitive decline in CLN3 disease.Methods Early neurocognitive functioning in CLN3 disease was analyzed using age at onset of visual and cognitive decline and IQ scores from literature-derived patient descriptions, supplemented with IQ scores and school history from a retrospective referral center cohort. We analyzed protracted and classical CLN3 separately and added a control group of patients diagnosed with juvenile onset macular degeneration (early onset Stargardt disease) to control for possible effects of rapid vision loss on neurocognitive functioning.Results Onset of cognitive decline at a mean age of 6.8 years (range 2-13 years, n = 19) paralleled onset of visual deterioration at a mean age of 6.4 years (range 4-9 years, n = 81) as supported by an early decline in IQ scores in classical CLN3 disease. Onset and course of vision loss was similar in patients with protracted CLN3. The decreased IQ levels at diagnosis (mean 68.4, range 57-79, n = 9) in the referral cohort were consistently associated with an aberrant early school history contrasting normal school history and cognition in Stargardt disease patients.Conclusions Cognitive dysfunction is universally present around diagnosis in classical CLN3 disease.