Motor function impairment is an early sign of CLN3 disease
Motor function impairment is an early sign of CLN3 disease
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DOI：
10.1212/wnl.0000000000007773
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发表时间：
2019-07-16
期刊：
影响因子：
9.9
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.
目的描述CLN 3疾病运动功能下降的时间。方法通过6分钟步行测试（6 MWT）评估运动功能，对15名CLN 3疾病患者进行重复评估，得到65个测试结果，并在2个对照队列中进行了一次评估。一个对照队列（n = 14）有孤立的视力损害;第二个队列（n = 12）表现出视力损害与神经功能障碍的组合。基于健康视力儿童的6 MWT参考值，计算CLN 3疾病患者和对照队列个体的6 MWT结果的z评分。6 MWT结果与年龄相关，包括多层次建模分析，允许评估不平衡的重复测量，并与统一巴滕疾病评定量表（UBDRS）scores.ResultsIn CLN 3疾病，6 MWT分数已经受损，从第一次测试近诊断（平均Z分数为-3.6和-4.7在7和8岁，分别）。之后，6 MWT评分随着年龄的增长（r =-0.64，p < 0.0001）和UBDRS评分的增加（r =-0.60，p = 0.0001）而持续下降，证实了与疾病进展的相关性。如CLN 3疾病中6 MWT结果的非线性多水平模型所示，这种降低在年龄较大时更为明显（y = 409.18 - [0.52 x年龄（2）]）。与此相反，在对照组中观察到6 MWT评分随年龄增长呈上升趋势（r = 0.56; p = 0.04），与健康视力正常儿童相似。额外的神经功能障碍的对照组显示出轻微下降的6 MWT步行距离独立于age.ConclusionsThe 6 MWT揭示早期发病的运动下降CLN 3疾病。
ObjectiveTo delineate timing of motor decline in CLN3 disease.MethodsMotor function, assessed by the 6-Minute Walk Test (6MWT), was evaluated repeatedly in 15 patients with CLN3 disease, resulting in 65 test results and during one occasion in 2 control cohorts. One control cohort (n = 14) had isolated visual impairment; a second cohort (n = 12) exhibited visual impairment in combination with neurologic impairments. Based on 6MWT reference values in healthy sighted children, z scores of 6MWT results in patients with CLN3 disease and control cohort individuals were calculated. 6MWT results were correlated with age-including multilevel modeling analysis allowing assessment of imbalanced repeated measurements-and with Unified Batten Disease Rating Scale (UBDRS) scores.ResultsIn CLN3 disease, 6MWT scores were already impaired from first testing near diagnosis (mean z scores of -3.6 and -4.7 at 7 and 8 years of age, respectively). Afterwards, 6MWT scores continuously declined with age (r = -0.64, p < 0.0001) and with increasing UBDRS scores (r = -0.60, p = 0.0001), confirming correlation with disease progression. The decrease was more pronounced at a later age, as shown by the nonlinear multilevel model for 6MWT results in CLN3 disease (y = 409.18 - [0.52 x age(2)]). In contrast, an upward trend of 6MWT scores with age was observed in the control cohort with isolated visual impairment (r = 0.56; p = 0.04) similar to healthy, sighted children. The control cohort with additional neurologic impairments displayed a slightly decreased 6MWT walking distance independent of age.ConclusionsThe 6MWT unveils early onset of motor decline in CLN3 disease.