Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
J Neurol. 2020 Jun;267(6):1643-1650. doi: 10.1007/s00415-020-09746-y. Epub 2020 Feb 14.
A randomized-controlled trial comparing study of the changes in brain sensitive-weighted imaging (SWI) of Wilson disease (WD) patients during the treatment with metal chelator was done.
100 untreated WD patients (80 cases of cerebral type, 20 cases of hepatic type, age 20.13 ± 9.12 years old) and 20 normal controls were selected. Neurological symptoms were scored using the modified Young scale. Liver function tests and copper indices were collected. All study objects received SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. Cerebral-type WD patients were treated with D-penicillamine (DPA) (group 1) or Dimercaptopropane Sulfonate (DMPS) + Dimercaptosuccinic Acid (DMSA) (group 2). Hepatic-type WD patients were treated with DPA (group 3). All patients received annual neurological symptom score, liver function, copper indices, and SWI examination.
At the first year of treatment, score of the modified Young scale in group 2 was lower than that in group 1 (P = 0.023) and lower than that before treatment (P = 0.040). After 2 years of treatment, the score of the modified Young scale in group 1 was lower than that before treatment (P = 0.012). At the second year after treatment, the urinary copper in group 2 was higher than that in group 1 (P = 0.014). Urinary copper was maintained at 200 µg/day in group 1 and 300 µg/day in group 2 after 3 years of treatment. At the first year of treatment, serum copper in group 1 was lower than that in group 2 (P = 0.032). At the first year of treatment, CP values of the pallidum and substantia nigra in group 2 were higher than those in group 1 (P = 0.026, 0.040). At the second year of treatment, CP value of substantia nigra in group 2 was higher than that in group 1 (P = 0.037). After 3 years of treatment, there was no difference in CP values between WD patients and normal controls.
Therapy with DMPS and DMSA improves neurological symptoms of WD patients more quickly and leads to less aggravation, compared with therapy with DPA. The metal content in the brain of WD patients was at a low level after 3 years of treatment. DMPS and DMSA can remove metal from brain tissue faster than DPA.
比较 Wilson 病（WD）患者在接受金属螯合剂治疗过程中脑敏感加权成像（SWI）变化的随机对照研究。
选取未经治疗的 WD 患者 100 例（脑型 80 例，肝型 20 例，年龄 20.13±9.12 岁）和 20 例正常对照。采用改良 Young 量表对神经症状进行评分。检测肝功能及铜指标。所有研究对象均行脑 SWI 检查，计算 SWI 校正相位（CP）值。脑型 WD 患者给予 D-青霉胺（DPA）（1 组）或二巯丁二酸二钠（DMPS）+二巯丁二酸（DMSA）（2 组）治疗，肝型 WD 患者给予 DPA（3 组）治疗。所有患者均接受年度神经症状评分、肝功能、铜指标和 SWI 检查。
治疗 1 年时，2 组改良 Young 量表评分低于 1 组（P=0.023）和治疗前（P=0.040），1 组低于治疗前（P=0.012）。治疗 2 年后，2 组尿铜高于 1 组（P=0.014）。治疗 3 年后，1 组尿铜维持在 200μg/d，2 组尿铜维持在 300μg/d。治疗 1 年时，1 组血清铜低于 2 组（P=0.032）。治疗 1 年时，2 组苍白球和黑质 CP 值高于 1 组（P=0.026、0.040）。治疗 2 年后，2 组黑质 CP 值高于 1 组（P=0.037）。治疗 3 年后，WD 患者 CP 值与正常对照组比较，差异无统计学意义。
与 DPA 治疗相比，DMPS 和 DMSA 治疗可更快改善 WD 患者的神经症状，导致病情恶化程度较轻。WD 患者脑内金属含量在治疗 3 年后处于较低水平。DMPS 和 DMSA 从脑组织中去除金属的速度快于 DPA。
