Acute-Onset Visual Impairment in Wilson's Disease: A Case Report and Literature Review.

Objective: We reported the case of a patient with Wilson's disease (WD) with acute-onset visual impairment and summarized previously reported cases to make physicians aware of the complicated clinical expressions of WD and improve diagnosis efficiency. Methods: The patient was recruited from the Second Affiliated Hospital of Zhejiang University School of Medicine. Clinical data, including cranial images, laboratory tests, and ophthalmic findings were obtained. The PubMed database was searched for published cases of WD with visual impairment. Results: We reported a 22-year-old male who presented with hand tremor, personality change, and acute-onset binocular vision blurring. WD was considered to be closely correlated with neuropsychiatric and ocular involvements. After low-copper diet and regular copper-chelation therapy, the related symptoms improved compared to before. Six WD cases of optic neuropathy have been reported, including ours. The patients usually had neurological and/or hepatic symptoms for a period without any treatment. All the reported cases manifested as acute episodes of visual changes, and the ocular manifestations improved after copper-chelation treatment. Conclusions: Excess copper accumulation may be a rare cause of visual impairment in patients with WD. While the etiology behind patients' acute-onset visual impairment remained uncertain, the possibility of WD should be considered through neuropsychiatric and hepatic symptoms, corneal K-F rings, decreased serum ceruloplasmin, and low likelihood or exclusion of other causes. Clinicians need to recognize this rare manifestation and give appropriate treatment to avoid misdiagnosis and unnecessary overtreatment.

Eomesodermin in CD4+T cells is essential for Ginkgolide K ameliorating disease progression in experimental autoimmune encephalomyelitis.

Eomesodermin (Eomes), a transcription factor, could suppress the Th17 cell differentiation and proliferation through directly binding to the promoter zone of the Rorc and Il17a gene, meanwhile the expression of Eomes is suppressed when c-Jun directly binds to its promoter zone. Ginkgolide K (1,10-dihydroxy-3,14-didehydroginkgolide, GK) is a diterpene lactone isolated from the leaves of Ginkgo biloba. A previous study indicated that GK could decrease the level of phospho JNK (c-Jun N-terminal kinase). Here, we reported the therapeutic potential of Ginkgolide K (GK) treatment to ameliorate experimental autoimmune encephalomyelitis (EAE) disease progression. Methods: EAE was induced in both wildtype and CD4-Eomes conditional knockout mice. GK was injected intraperitoneally. Disease severity, inflammation, and tissue damage were assessed by clinical evaluation, flow cytometry of mononuclear cells (MNCs), and histopathological evaluation. Dual-luciferase reporter assays were performed to measure Eomes transcription activity in vitro. The potency of GK (IC50) was determined using JNK1 Kinase Enzyme System. Results: We revealed that GK could ameliorate EAE disease progression by the inhibition of the Th17 cells. Further mechanism studies demonstrated that the level of phospho JNK was decreased and the level of Eomes in CD4+T cells was dramatically increased. This therapeutic effect of GK was almost completely interrupted in CD4-Eomes conditional knockout mice. Conclusions: These results provided the therapeutic potential of GK treatment in EAE, and further suggested that Eomes expression in CD4+T cells might be essential in this process.

Clinical features and outcome of Wilson's disease with generalized epilepsy in Chinese patients.

OBJECTIVE: Generalized epilepsy is rarely reported in patients with Wilson disease (WD) and lacks experience in clinical practice. We aim to provide better experience for the diagnosis and treatment for WD patients with epilepsy in the future. METHODS: A retrospective study was performed in 13 Chinese WD patients with generalized epilepsy. Each patient was diagnosed with WD by clinical evaluation and genetic screening. Patients were given small doses of antiepileptic drugs (AEDs), followed by copper-chelation therapy when the seizures stabilized. Clinical manifestations, brain imaging changes, and treatment and outcome after a long-term follow-up were analyzed. RESULTS: Four out of 13 (30.8%) patients stopped taking copper-chelation drugs for more than 1 year before they were admitted for epilepsy. The incidence of epilepsy of WD patients in our cohort is 1.43% (13/910), lower than those (4.5%-5.9%) in other populations. After the attack of epilepsy, frontal lobes were the most common abnormalities (13/13, 100%) in patients, followed by brain stem (8/13, 61.5%) and thalamus (7/13, 53.8%). After a long-term follow-up, brain imaging and clinical manifestations of 8 (8/9, 88.9%) WD patients were significantly improved. CONCLUSIONS: We firstly described WD patients with generalized epilepsy in the Chinese population. WD patients with aggravation of neuropsychiatric symptoms are prone to occur epilepsy; thus, brain MRI should be performed regularly in those patients. Cortical abnormality in brain MRI is a warning sign of epilepsy. Irregular use of copper-chelation drugs and excessive copper deposition in the brain may be the cause of seizures. Long-term standardized treatment for WD can effectively prevent the extensive brain damage and reduce the incidence of epilepsy in WD patients.

Clinical features and outcome in patients with osseomuscular type of Wilson's disease.

BACKGROUND: Wilson's disease with osseomuscular type is a rare condition, which often lacks typical hepatic and neurological symptoms and causes misdiagnoses easily. During the past 10 years, eight Chinese patients of osseomuscular type of Wilson's disease were identified in our clinic. METHODS: Clinical information was gathered from medical records and follow-ups. The genetic testing was performed in each patient. Serum ceruloplasmin, Kayser-Fleischer rings, liver function, brain magnetic resonance imaging and abdominal ultrasonography were also evaluated. RESULTS: The median age of onset is 12 years of age. The patients had their initial musculoskeletal conditions with arthralgia or joint deformity, while the hepatic or neurologic signs were minimal. Most patients (6/8) eventually developed clinical neurological symptoms afterwards with a median interval of 36 months. All of them had normal liver function and low serum ceruloplasmin (<0.1 g/L). Most patients (6/8) present with Kayser-Fleischer rings and abnormal hepatic ultrasonography. The arthralgia was resolved with copper chelation therapy. CONCLUSIONS: Wilson's disease with osseomuscular type occurs without typical hepatic or neurological symptoms, which makes the clinical diagnosis challenging. Serum ceruloplasmin, abdominal ultrasonography, ophthalmic examination and genetic testing help to establish the diagnosis. Early diagnosis can initiate an effective treatment and prevent the further damage.

[Characteristics of Nitrogen and Phosphorus Losses in Longhong Ravine Basin of Westlake in Rainstorm Runoff].

In order to understand the non-point source pollution status in Longhong ravine basin of Westlake, the characteristics of nutrient losses in runoff was investigated during three rainstorms in one year. The results showed that long duration rainstorm event generally formed several runoff peaks, and the time of its lag behind the peaks of rain intensity was dependent on the distribution of heavy rainfall. The first flush was related to the antecedent rainfall, and the less rainfall in the earlier period, the more total phosphorus (TP) and ammonia (NH4+ -N) in runoff was washed off. During the recession of runoff, more subsurface runoff would result in a concentration peak of total nitrogen (TN) and nitrogen (NO3- -N) . The event mean concentration (EMC) of runoff nitrogen had a negative correlation with rainfall, rainfall duration, maximum rain intensity and average rain intensity except for antecedent rainfall, whereas the change in TP EMC showed the opposite trend. The transport fluxes of nutrients increased with an elevation in runoffs, and Pearson analysis showed that the transport fluxes of TN and NO3- -N had good correlations with runoff depth. The average transport fluxes of TP, TN, NH4+ -N and NO3- -N were 34.10, 1195.55, 1006.62 and 52.38 g x hm(-2), respectively, and NO3- -N was the main nitrogen form and accounted for 84% of TN.

Early Application of Auxiliary Partial Orthotopic Liver Transplantation in Murine Model of Wilson Disease.

BACKGROUND: Liver transplantation (LT) is the only option of treatment for Wilson disease (WD) when chelation therapy fails, but it is limited due to the shortage of donor. Auxiliary partial orthotopic LT (APOLT) has been performed successfully in end-stage WD patients, which expands the donor pool. METHODS: Atp7bmice were used as experimental model of WD. Eight- and 20-week-old mice were used as different timepoints to perform APOLT. Serum copper, tissue copper, serum ceruloplasmin (CP), and liver histological examination were observed after operation. RESULTS: Hepatic and serum copper levels in Atp7b mice decreased after APOLT, and copper metabolism disorder of WD mice was relieved at both early and late stages. The progression of pathology in the native liver was delayed only when transplantation was performed at an early stage. CONCLUSIONS: Auxiliary partial orthotopic LT can significantly improve copper metabolism disorder in the Atp7b mice, and early transplantation may prevent the disease progression.