Kalita Jayantee, Kumar Vijay, Ranjan Abhay, Misra Usha K
Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Raebareily Road, Lucknow, 226014, India.
Neuromolecular Med. 2015 Dec;17(4):364-72. doi: 10.1007/s12017-015-8364-8. Epub 2015 Jul 30.
Patients with neurologic Wilson disease (NWD) may worsen on treatment, but there is no study evaluating the role of oxidative stress. We report the role of plasma glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA) in the worsening of NWD following treatment. Fifty-one treatment-naïve NWD patients were subjected to detailed clinical evaluation. The severity of NWD was noted, and dystonia was measured by Burke-Fahn-Marsden (BFM) score. Their hematological, serum chemistry, ultrasound abdomen and cranial MRI changes were noted. Plasma GSH, TAC and MDA, serum free copper (Cu) and 24-h urinary Cu were measured at admission and at 3 and 6 months after treatment. The patients were considered worsened if there was one or more grade deterioration in severity scale, >10 % deterioration in BFM score or appearance of new neurologic signs. The median age of the patients was 11 (5-37) years, and 12 were females. Following treatment, 25 patients improved, 12 worsened, and 14 had stationary course. The worsened group at 3 months had lower GSH (1.99 ± 0.17 vs. 2.30 ± 0.30 mg/dl; P = 0.004) and TAC (1.59 ± 0.12 vs. 1.82 ± 0.17 mmol Trolox equivalent/L; P = 0.001) and higher MDA (5.24 ± 0.22 vs. 4.34 ± 0.46 nmol/ml; P < 0.001) levels compared to the improved group. These changes were associated with increased serum free Cu (41.81 ± 3.31 vs. 35.62 ± 6.40 µg/dl; P = 0.02) and 24-h urinary Cu (206.42 ± 41.61 vs. 121.99 ± 23.72 µg/24 h; P < 0.001) in the worsened compared to the improved group. All the patients having worsening were on penicillamine. Worsening following chelating treatment in NWD may be due to oxidative stress which is induced by increased serum free Cu. These results may have future therapeutic implication and needs further study.
患有神经型威尔逊病（NWD）的患者在治疗过程中病情可能会恶化，但尚无研究评估氧化应激在此过程中的作用。我们报告了血浆谷胱甘肽（GSH）、总抗氧化能力（TAC）和丙二醛（MDA）在NWD治疗后病情恶化中的作用。对51例未经治疗的NWD患者进行了详细的临床评估。记录NWD的严重程度，并用伯克-法恩-马斯登（BFM）评分法测量肌张力障碍。记录他们的血液学、血清化学、腹部超声和头颅MRI变化。在入院时以及治疗后3个月和6个月测量血浆GSH、TAC和MDA、血清游离铜（Cu）和24小时尿铜。如果严重程度量表中有一个或多个等级恶化、BFM评分恶化超过10%或出现新的神经体征，则认为患者病情恶化。患者的中位年龄为11（5-37）岁，女性12例。治疗后，25例患者病情改善，12例恶化，14例病情稳定。与病情改善组相比，恶化组在3个月时GSH水平较低（1.99±0.17 vs. 2.30±0.30 mg/dl；P = 0.004）、TAC水平较低（1.59±0.12 vs. 1.82±0.17 mmol Trolox当量/L；P = 0.001），而MDA水平较高（5.24±0.22 vs. 4.34±0.46 nmol/ml；P < 0.001）。与病情改善组相比，恶化组的这些变化与血清游离铜增加（41.81±3.31 vs. 35.62±6.40 µg/dl；P = 0.02）和24小时尿铜增加（206.42±41.61 vs. 121.99±23.72 µg/24 h；P < 0.001）有关。所有病情恶化的患者均使用青霉胺治疗。NWD患者螯合治疗后病情恶化可能是由于血清游离铜增加诱导的氧化应激所致。这些结果可能具有未来的治疗意义，需要进一步研究。
