title: Role of Oxidative Stress in the Worsening of Neurologic Wilson Disease Following Chelating Therapy.
abstract: 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.
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Raebareily Road, Lucknow, 226014, India. jayanteek@yahoo.com.
authors.forename: Jayantee
authors.initials: J
authors.lastname: Kalita
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Raebareily Road, Lucknow, 226014, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Raebareily Road, Lucknow, 226014, India.
authors.forename: Abhay
authors.initials: A
authors.lastname: Ranjan
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Raebareily Road, Lucknow, 226014, India.
authors.forename: Usha K
authors.initials: UK
authors.lastname: Misra
mesh_terms: D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000032:analysis; D002614:Chelating Agents / Q000009:adverse effects*; D015913:Chelation Therapy / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003300:Copper / Q000097:blood / Q000652:urine; D018450:Disease Progression; D005260:Female; D005978:Glutathione / Q000097:blood; D006527:Hepatolenticular Degeneration / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D019934:International Normalized Ratio; D007668:Kidney / Q000503:physiopathology; D015227:Lipid Peroxidation; D008099:Liver / Q000000981:diagnostic imaging / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress; D010396:Penicillamine / Q000009:adverse effects* / Q000627:therapeutic use; D012720:Severity of Illness Index; D013154:Spleen / Q000000981:diagnostic imaging; D016896:Treatment Outcome; D014463:Ultrasonography; D055815:Young Adult; D015032:Zinc / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D002614:Chelating Agents; D008315:Malondialdehyde; D003300:Copper; D005978:Glutathione; D010396:Penicillamine; D015032:Zinc
keywords: Copper; Glutathione; Lipid peroxidation; Oxidative stress; Total antioxidant capacity; Wilson disease