MRI and oxidative stress markers in neurological worsening of Wilson disease following penicillamine

Ranjan, Abhay; Kalita, Jayantee; Kumar, Vijay; Misra, Usha Kant

doi:10.1016/j.neuro.2015.05.004

Cited by 24 publications

(18 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Brain lesions may be present in multiple sites in WD, exhibiting symmetry abnormal signal in bilateral hemisphere mostly [15]. In the present study, we found that the lenticular nucleus was the most commonly affected site, and the hippocampus and cerebellum were the least, a finding that was consistent with a previous report [16].…”

Section: Discussionsupporting

confidence: 93%

A study of brain MRI characteristics and clinical features in 76 cases of Wilson’s disease

Wang

Huang

Tang

2019

Journal of Clinical Neuroscience

View full text Add to dashboard Cite

To explore the value of brain MRI in Wilson's disease (WD) in relating neurological symptoms with clinical manifestations of the disease, a retrospective analysis of 76 WD patients with neurological symptoms was performed. Patients' neurological symptoms, brain MRI features, and laboratory findings were noted. MRI was abnormal in 89.5% of patients. The lenticular nucleus was the most commonly lesioned site, being affected in 75% of patients, followed by the caudate nucleus (lesioned in 30.9% of patients), pons (30.9%), thalamus (29.4%), midbrain (20.6%), cerebral cortex and white matter (5.9% of patients in each case), and cerebellum and hippocampus (4.4% in each case). Brain atrophy was also relatively common, occurring in 31.6% of subjects. We also determined that the sensitivity of T2 was 89.7%, while that of T1 and FLAIR were both 76.5%. 23 patients were scanned without the benefit of contrast enhancement, and of the 8 patients who were scanned with DWI, 6 exhibited hypointensities, while 2 were normal. The 5 patients who underwent susceptibility-weighted imaging (SWI) all showed hypointensities. A longer disease duration appeared to be more prevalent when thalamic abnormalities were observed, and tremor seemed to be correlated with cerebral atrophy. Ataxia was correlated with brainstem, cerebellar, and cerebral cortex lesions. It was determined that the T2 sequence has a higher sensitivity compared to T1 and FLAIR in the detection of brain lesions.

show abstract

Section: Discussionsupporting

confidence: 93%

A study of brain MRI characteristics and clinical features in 76 cases of Wilson’s disease

Wang

Huang

Tang

2019

Journal of Clinical Neuroscience

View full text Add to dashboard Cite

show abstract

“…Preexisting damage to the glial system in neurologic WD may not be able to clear the oxidative stress leading to enhanced brain damage. On MRI, we have noticed increased T2 hyperintensity and diffusion restriction, especially in the white matter during neurologic deterioration (Ranjan et al 2015). In our earlier study, we have reported increased MDA, cytokines (interleukin 6, 8, 10 and tumor necrosis factor a), glutamate and reduced GSH and TAC in the WD patients.…”

Section: Discussionmentioning

confidence: 80%

Role of Oxidative Stress in the Worsening of Neurologic Wilson Disease Following Chelating Therapy

2015

View full text Add to dashboard Cite

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.

show abstract

“…This drug favors urinary excretion of copper, but it also induces the endogenous intracellular Neurological damage, in some cases irreversible, may be induced by massive and sudden free copper elevation following therapy with D-penicillamine and other potent chelators [78] ; neurological worsening has in fact been linked with spikes in free copper, induced by chelators including D-penicillamine [79,80] . The mechanism behind neurological worsening is the mobilization of important amounts of free copper, which together with an increase in malanodialdehyde and a reduction in glutathione, lead to cellular damage [81] . Moreover, due to its effects on collagen formation and thus on wound healing, D-penicillamine must be suspended (and therapy changed to zinc or trientine) between 2 to 3 mo before planned surgery.…”

Section: D-penicillaminementioning

confidence: 99%

Wilson’s disease: A review of what we have learned

Rodríguez–Castro

Hevia‐Urrutia

Sturniolo

2015

WJH

134

123

View full text Add to dashboard Cite

Wilson's disease (WD), which results from the defective ATP7B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury.

show abstract

MRI and oxidative stress markers in neurological worsening of Wilson disease following penicillamine

Cited by 24 publications

References 24 publications

A study of brain MRI characteristics and clinical features in 76 cases of Wilson’s disease

A study of brain MRI characteristics and clinical features in 76 cases of Wilson’s disease

Role of Oxidative Stress in the Worsening of Neurologic Wilson Disease Following Chelating Therapy

Wilson’s disease: A review of what we have learned

Contact Info

Product

Resources

About