Study on different pathogenic factors in different disease stages of patients with Wilson disease.

OBJECTIVE: To investigate in different stages of patients with Wilson disease (WD), there are different pathogenic factors such as metal deposition, oxidative stress, and inflammatory response in the brain. METHODS: A total of 32 untreated WD patients and 10 normal controls were enrolled in the study. The neurological symptoms were evaluated using the modified Young scale. Liver function, metal metabolism, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) examination were done. The clinical disease stages were divided into metal deposition period, fiber damage period, and neuronal necrosis period according to the imaging results. The content of 24-h urine copper, serum copper, and serum iron; and the levels of catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), interleukin (IL-1), and tumor necrosis factor alpha (TNF-α) were detected. RESULTS: The contents of urinary copper in WD patients at neuronal necrosis stage were lower than those in patients at the metal deposition stage (P = 0.011) and fiber injury stage (P = 0.023). The contents of NOS (P = 0.039) and NO (P = 0.047) in WD patients at the stage of fiber injury were higher than those of the normal control, while GSH-PX (P = 0.025) and CAT (P = 0.041) were lower in the neuronal necrosis stage. In the stage of neuronal necrosis, the levels of IL-1 (P = 0.030) and TNF-α were higher than those of the normal control (P = 0.042). The neurological symptom scores in patients with fiber injury (P = 0.013) and neuron injury were higher than those with metal deposition (P = 0.026). CONCLUSION: There are different pathogenic factors in different stages of WD. At the neuronal necrosis stage, copper deposition was decreased in WD patients. In the stage of fiber injury and neuronal necrosis, there is oxidative stress injury in WD patients. In the neuronal necrosis phase, WD patients have an inflammatory response.

A study of susceptibility-weighted imaging in patients with Wilson disease during the treatment of metal chelator.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.