Construction of a nomogram for predicting compensated cirrhosis with Wilson's disease based on non-invasive indicators.

BACKGROUND: Wilson's disease (WD) often leads to liver fibrosis and cirrhosis, and early diagnosis of WD cirrhosis is essential. Currently, there are few non-invasive prediction models for WD cirrhosis. The purpose of this study is to non-invasively predict the occurrence risk of compensated WD cirrhosis based on ultrasound imaging features and clinical characteristics. METHODS: A retrospective analysis of the clinical characteristics and ultrasound examination data of 102 WD patients from November 2018 to November 2020 was conducted. According to the staging system for WD liver involvement, the patients were divided into a cirrhosis group (n = 43) and a non-cirrhosis group (n = 59). Multivariable logistic regression analysis was used to identify independent influencing factors for WD cirrhosis. A nomogram for predicting WD cirrhosis was constructed using R analysis software, and validation of the model's discrimination, calibration, and clinical applicability was completed. Due to the low incidence of WD and the small sample size, bootstrap internal sampling with 500 iterations was adopted for validation to prevent overfitting of the model. RESULTS: Acoustic Radiation Force Impulse (ARFI), portal vein diameter (PVD), and serum albumin (ALB) are independent factors affecting WD cirrhosis. A nomogram for WD cirrhosis was constructed based on these factors. The area under the ROC curve (AUC) of the model's predictive ability is 0.927 (95% CI: 0.88-0.978). As demonstrated by 500 Bootstrap internal sampling validations, the model has high discrimination and calibration. Clinical decision curve analysis shows that the model has high clinical practical value. ROC curve analysis of the model's rationality indicates that the model's AUC is greater than the AUC of using ALB, ARFI, and PVD alone. CONCLUSION: The nomogram model constructed based on ARFI, PVD, and ALB can serve as a non-invasive tool to effectively predict the risk of developing WD cirrhosis.

Resolution of Wing-Beating Tremor and Magnetic Resonance Imaging Lesions in Wilson's Disease Following Penicillamine.

Background: The wing-beating tremor, characteristic of Wilson's disease (WD), is a disabling symptom that can be resistant to anti-copper and anti-tremor medications. Phenomenology Shown: This video illustrates severe bilateral wing-beating tremor, moderate head and lower limb tremors, mild cervical dystonia, and subtle cerebellar ataxia, with nearly resolution after penicillamine treatment. Educational Value: This case highlights a typical aspect of WD, emphasizing the importance of early detection and treatment, and its correlation with MRI findings. Highlights: This case highlights the typical wing-beating tremor in Wilson's disease and its correlation with the involvement of the dentato-rubro-thalamic pathway. The early diagnosis and initiation of treatment with penicillamine resulted in an excellent clinical and radiological response.

Teaching NeuroImage: Neuroimaging Features of Wilson Disease.

A 13-year-old boy of nonconsanguineous parents presented with abnormal body movements, gait difficulty, and slurring of speech for 2 years. On examination, he had rigidity, dystonia, dysarthria, and drooling. Ophthalmologic examination revealed bilateral Kayser-Fleischer rings. He had elevated serum "free" copper levels (41.2 µg/dL [range:10-15]), 24-hour urine copper levels (895.7 µg/d [range:<60]), and reduced serum ceruloplasmin levels (4.3 mg/dL (range:20-40]). MRI revealed "face of giant panda" appearance (Figure A), T2-fluid attenuated inversion recovery hyperintensities (Figure, B and C), and frontal cystic encephalomalacic changes (Figure D), suggestive of Wilson disease (WD). Face of giant panda in WD, first described by Hitoshi et al.,1 is due to high signal intensity in tegmentum with normal signals in red nuclei forming the eyes, normal signals of pars reticulata (lateral portion) of substantia nigra forming the ears, and hypointensity of superior colliculus forming the chin.2 Bilateral cystic changes are less commonly reported in WD.3 Recognizing diverse neuroimaging signatures beyond well-known findings in WD enhances diagnostic accuracy.

A case of Wilson's disease combined with intracranial lipoma and dysplasia of the corpus callosum with review of the literature.

BACKGROUND: Wilson's disease (WD) is an inherited disorder of copper metabolism. Agenesis of the corpus callosum is the complete or partial absence of the major united fiber bundles connecting the cerebral hemispheres. Intracranial lipoma is an adipose tissue tumor resulting from an abnormal embryonic development of the central nervous system. The simultaneous occurrence of these three disorders is rare and has not been reported. This report focuses on the pathogenesis and association between the three disorders and highlights the importance of recognizing and effectively managing their coexistence. CASE PRESENTATION: The purpose of this study was to present a patient with coexisting WD, intracranial lipoma, and corpus callosum dysplasia. We reviewed a female patient hospitalized in 2023 with clinical manifestations of elevated aminotransferases and decreased ceruloplasmin, as well as genetic testing for an initial diagnosis of Wilson's disease. Subsequently, a cranial MRI showed corpus callosum dysplasia with short T1 signal changes in the cerebral falx, leading to a final diagnosis of Wilson's disease combined with intracranial lipoma and corpus callosum dysplasia. The patient's WD is currently stable after treatment with sodium dimercaptosulfonamide (DMPS) and penicillamine, and the patient's abnormal copper metabolism may promote the growth of intracranial lipoma. CONCLUSION: The pathogenesis of WD combined with intracranial lipoma and corpus callosum dysplasia is complex and clinically rare. The growth of intracranial lipomas may be associated with abnormal copper metabolism in WD. Abnormal copper metabolism affects lipid metabolism and triggers inflammatory responses. Therefore, early diagnosis and treatment are beneficial for improvement. Each new case of this rare co-morbidity is important as it allows for a better assessment and understanding of these cases' more characteristic clinical manifestations, which can help estimate the course of the disease and possible therapeutic options.

The volume and structural covariance network of thalamic nuclei in patients with Wilson's disease: an investigation of the association with neurological impairment.

OBJECTIVE: This study aimed to examine the volumes of thalamic nuclei and the intrinsic thalamic network in patients with Wilson's disease (WDs), and to explore the correlation between these volumes and the severity of neurological symptoms. METHODS: A total of 61 WDs and 33 healthy controls (HCs) were included in the study. The volumes of 25 bilateral thalamic nuclei were measured using structural imaging analysis with Freesurfer, and the intrinsic thalamic network was evaluated through structural covariance network (SCN) analysis. RESULTS: The results indicated that multiple thalamic nuclei were smaller in WDs compared to HCs, including mediodorsal medial magnocellular (MDm), anterior ventral (AV), central median (CeM), centromedian (CM), lateral geniculate (LGN), limitans-suprageniculate (L-Sg), reuniens-medial ventral (MV), paracentral (Pc), parafascicular (Pf), paratenial (Pt), pulvinar anterior (PuA), pulvinar inferior (PuI), pulvinar medial (PuM), ventral anterior (VA), ventral anterior magnocellular (VAmc), ventral lateral anterior (VLa), ventral lateral posterior (VLp), ventromedial (VM), ventral posterolateral (VPL), and right middle dorsal intralaminar (MDI). The study also found a negative correlation between the UWDRS scores and the volume of the right MDm. The intrinsic thalamic network analysis showed abnormal topological properties in WDs, including increased mean local efficiency, modularity, normalized clustering coefficient, small-world index, and characteristic path length, and a corresponding decrease in mean node betweenness centrality. WDs with cerebral involvement had a lower modularity compared to HCs. CONCLUSIONS: The findings suggest that the majority of thalamic nuclei in WDs exhibit significant volume reduction, and the atrophy of the right MDm is closely related to the severity of neurological symptoms. The intrinsic thalamic network in WDs demonstrated abnormal topological properties, indicating a close relationship with neurological impairment.

Changes in brain susceptibility in Wilson's disease patients: a quantitative susceptibility mapping study.

AIM: To assess changes in the susceptibility of the caudate nucleus (CN), putamen, and globus pallidus (GP) in patients with neurological and hepatic Wilson's disease (WD) by quantitative susceptibility mapping (QSM). MATERIAL AND METHODS: The brain MRI images of 33 patients diagnosed with WD and 20 age-matched controls were analysed retrospectively. All participants underwent brain T1-weighted, T2-weighted, and QSM imaging using a 1.5 T magnetic resonance imaging (MRI) machine. QSM maps were evaluated with the STISuite toolbox. The quantitative susceptibility levels of the CN, putamen, and GP were analysed using region of interest analysis on QSM maps. Differences among neurological WD patients, hepatic patients, and controls were determined. RESULTS: Susceptibility levels were significantly higher for all examined structures (CN, putamen and GP) in patients with neurological WD compared with controls (all p<0.05) and hepatic WD patients (all p<0.05). No statistically significant differences were found in susceptibility levels between patients with hepatic WD and controls (all p>0.05). CONCLUSION: The QSM technique is a valuable tool for detecting changes in brain susceptibility in WD patients, indicating abnormal metal deposition. Notably, the current findings suggest that neurological WD patients exhibit more severe susceptibility changes compared with hepatic WD patients. Therefore, QSM can be utilised as a complementary method to detect brain injury in WD patients.

Large-scale networks changes in Wilson's disease associated with neuropsychiatric impairments: a resting-state functional magnetic resonance imaging study.

BACKGROUND: In Wilson's disease (WD) patients, network connections across the brain are disrupted, affecting multidomain function. However, the details of this neuropathophysiological mechanism remain unclear due to the rarity of WD. In this study, we aimed to investigate alterations in brain network connectivity at the whole-brain level (both intra- and inter-network) in WD patients through independent component analysis (ICA) and the relationship between alterations in these brain network functional connections (FCs) and clinical neuropsychiatric features to understand the underlying pathophysiological and central compensatory mechanisms. METHODS: Eighty-five patients with WD and age- and sex-matched 85 healthy control (HC) were recruited for resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We extracted the resting-state networks (RSNs) using the ICA method, analyzed the changes of FC in these networks and the correlation between alterations in FCs and clinical neuropsychiatric features. RESULTS: Compared with HC, WD showed widespread lower connectivity within RSNs, involving default mode network (DMN), frontoparietal network (FPN), somatomotor network (SMN), dorsal attention network (DAN), especially in patients with abnormal UWDRS scores. Furthermore, the decreased FCs in the left medial prefrontal cortex (L_ MPFC), left anterior cingulate gyrus (L_ACC), precuneus (PCUN)within DMN were negatively correlated with the Unified Wilson's Disease Rating Scale-neurological characteristic examination (UWDRS-N), and the decreased FCs in the L_MPFC, PCUN within DMN were negatively correlated with the Unified Wilson's Disease Rating Scale-psychiatric symptoms examination (UWDRS-P). We additionally discovered that the patients with WD exhibited significantly stronger FC between the FPN and DMN, between the DAN and DMN, and between the FPN and DAN compared to HC. CONCLUSIONS: We have provided evidence that WD is a disease with widespread dysfunctional connectivity in resting networks in brain, leading to neurological features and psychiatric symptoms (e.g. higher-order cognitive control and motor control impairments). The alter intra- and inter-network in the brain may be the neural underpinnings for the neuropathological symptoms and the process of injury compensation in WD patients.

Clinical Spectrum, Radiological Correlation and Outcome of Movement Disorders in Wilson's Disease.

Introduction: Movement disorders are the commonest clinical presentation in patients with neurological Wilson's disease (NWD). There are very few studies evaluating the spectrum, severity and their correlation with magnetic resonance imaging (MRI) changes of movement disorders in NWD. Objective: To study the spectrum, topographic distribution, radiological correlate, temporal course and outcome in our cohort of NWD patients. Methods: Retrospective chart review of the NWD patients having movement disorders was performed and analyzed. Results: Sixty-nine patients (males- 47) with NWD were analysed and the mean age at the onset of neurological symptoms was 13.6 ± 6.6 years (median 13 years; range 7-37 years). The first neurological symptom was movement disorder in 55 (79.7%) patients. Tremor (43.6%) and dystonia (41.8%) was the commonest movement disorder as the first neurological symptom. Dystonia (76.8%) was the most common overall movement disorder followed by parkinsonism (52.1%) and tremors (47.8%). Chorea (10.1%), myoclonus (1.4%) and ataxia (1.4%) were the least common movement disorder. Putamen was the most common affected site (95.6%) followed by caudate nucleus (73.9%), thalamus (60.8%), midbrain (59.4%), internal capsule (49.2%), pons (46.3%). Putamen was the most common area of abnormality in dystonia (98%), tremors (85%). Caudate (75%) and putamen (75%) was the most common areas of abnormality in parkinsonism. Favourable outcome was observed in 42 patients (60.8%) following treatment. Conclusion: Dystonia is the most common movement disorder in NWD in isolation or in combination with parkinsonism and tremors. Putamen is the most common radiological site of lesions and more frequently affected in patients with dystonia and tremors. Favourable outcome does occur with appropriate medical and surgical treatment.

Symptom aggravation after withdrawal of metal chelating agent therapy in patients with Wilson's disease.

OBJECTIVE: To study the aggravation of clinical symptoms after discontinuation of metal chelating agent therapy in Wilson's disease (WD) patients, analyze the causes of aggravation, and observe the prognosis. METHODS: 40 WD patients (cerebral type 30 cases and hepatic type 10 cases) who stopped using metal chelating agent were selected, 40 WD patients with normal therapy, and 10 normal control cases were selected. All patients underwent neurological symptom evaluation using modified Young scale, Child-Pugh liver function grading, metal metabolism, and disease typing. Magnetic sensitivity imaging (SWI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy imaging (MRS) were performed. According to the imaging results, WD patients were divided into metal deposition stage, fiber damage stage, and neuron necrosis stage. All patients were treated with metal chelating agent for 6 months. RESULTS: The score of modified Young scale in drug withdrawal group was lower than that in normal treatment group before drug withdrawal (p = .032). The score of modified Young scale was higher after drug withdrawal than before (p = .011). The number of Child-Pugh B-grade patients after drug withdrawal was more than that before drug withdrawal and in normal treatment group. The proportion of patients in the stage of neuronal necrosis after drug withdrawal (25%) was higher than that before drug withdrawal (10%) (p = .025). After drug withdrawal, urine copper was significantly higher than that before drug withdrawal and in the normal treatment group (p = .032, .039). After the withdrawal group resumed metal chelating agent treatment, 34.2% of neurological symptoms worsened. CONCLUSIONS: WD patients showed neurological symptoms aggravation and increased liver injury after metal chelating agent withdrawal. Increased metal deposition and new nerve injury occurred in the brain. After re-treatment, the aggravated neurological symptoms of WD patients are difficult to reverse.

Metal deposits associated with brain atrophy in the deep gray matter nucleus in Wilson's disease.

Regional atrophy and metal deposition are typical manifestations in Wilson's disease, but their relationship has not been systematically investigated. We aim to investigate the association of regional brain atrophy and metal deposition in the deep gray matter nucleus at MRI in Wilson's disease. We acquired the structural and susceptibility mapping and performed a cross-sectional comparison of volume and susceptibility in deep gray matter nucleus. The most extensive and severe atrophy was detected in brain regions in neuro-Wilson's disease, as well as the most widespread and heaviest metal deposits. Metal deposits were significantly negatively correlated with volume in the bilateral thalamus, caudate, and putamen. None of correlation was found between the clinical score with volume or susceptibility in the focused regions. In the 1-year follow-up analysis, the volume of right thalamus, globus pallidus, and brainstem and the susceptibility of the left caudate have decreased significantly as the symptom improvement. In Wilson's disease, phenotypes have varied scope and extend of volumetric atrophy and metal deposits. This study is expected to take the lead in revealing that in neuro-Wilson's disease, greater regional atrophy associated with heavier metal deposits in Wilson's disease. Moreover, after 1-year treatment, the imaging data have changed as the patient's condition improvement.

Optical coherence tomography in patients with Wilson's disease.

BACKGROUND: Morphological changes of retina in patients with Wilson's disease (WD) can be found by optical coherence tomography (OCT), and such changes had significant differences between neurological forms (NWD) and hepatic forms (HWD) of WD. The aim of this study was to evaluate the relationship between morphological parameters of retina and brain magnetic resonance imaging (MRI) lesions, course of disease, type of disease, and sexuality in WD. METHODS: A total of 46 WD patients and 40 health controls (HC) were recruited in this study. A total of 42 WD patients were divided into different groups according to clinical manifestations, course of disease, sexuality, and brain MRI lesions. We employed the Global Assessment Scale to assess neurological severity of WD patients. All WD patients and HC underwent retinal OCT to assess the thickness of inner limiting membrane (ILM) layer to retinal pigment epithelium layer and inner retina layer (ILM to inner plexiform layer, ILM-IPL). RESULTS: Compared to HWD, NWD had thinner superior parafovea zone (108.07 ± 6.89 vs. 114.40 ± 5.54 µm, p < .01), temporal parafovea zone (97.17 ± 6.65 vs. 103.60 ± 4.53 µm, p < .01), inferior parafovea zone (108.114 ± 7.65 vs. 114.93 ± 5.84 µm, p < .01), and nasal parafovea zone (105.53 ± 8.01 vs. 112.10 ± 5.44 µm, p < .01) in inner retina layer. Course of disease influenced the retina thickness. Male patients had thinner inner retina layer compared to female patients. CONCLUSION: Our results demonstrated that WD had thinner inner retina layer compared to HC, and NWD had thinner inner retina layer compared to HWD. We speculated the thickness of inner retina layer may be a potential useful biomarker for NWD.

Vascular changes in macula, optic disc, and choroid in Wilson's disease: A cross-sectional optical coherence tomography angiography study.

PURPOSE: To evaluate the changes in the retinal and optic disc (OD) microcirculation in patients with Wilson's disease (WD) using optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: This cross-sectional comparative study included 35 eyes of 35 WD patients (study group) and 36 eyes of 36 healthy participants (control group). The patients with WD were divided into subgroups based on the presence of Kayser-Fleischer rings. All the participants underwent a comprehensive ophthalmological examination, including OCTA. RESULTS: The inferior perifoveal deep capillary plexus vessel density (DCP-VD), inferior radial peripapillary capillary vessel density (RPC-VD), and inferior peripapillary retinal nerve fiber layer (PPRNFL) thickness were significantly lower in the WD group than in the healthy participants (p=0.041, p=0.043, and p=0.045, respectively). In addition, in the subgroup analysis, the superior RPC-VD and inferior PPRNFL were significantly lower in the subgroup with Kayser-Fleischer rings (p=0.013 and p=0.041, respectively). CONCLUSION: We showed there to be changes in certain OCTA parameters in WD patients when compared with healthy controls. Thus, we hypothesized that OCTA could detect any retinal microvascular changes in WD patients without clinical evidence of retinal or OD involvement.

Computed tomography of hyper-attenuated liver: Pictorial essay.

Demonstration of a very dense or hyper-attenuated liver on the pre-contrast CT images of the abdomen can be an unexpected finding. It may present as a diagnostic challenge if the underlying cause of it is not apparent from the provided clinical history. There are about 12 different pathologic conditions that are associated with deposition of radiopaque elements within the hepatic parenchyma, resulting in diffuse or multi-lobar hyperdense appearance of the liver on abdominal radiographs and CT. Most of them are drug-induced or iatrogenic in nature, while others are the sequelae of genetic disorders like thalassemia, Wilson's disease, and primary hemochromatosis. This pictorial essay will present the CT appearance and etiology of hyper-attenuated liver in various clinical entities.

Application of attenuation coefficient in the assessment of hepatic involvement in children and adolescents with Wilson's disease.

BACKGROUND: To investigate whether the attenuation coefficient (ATT) can be used as a noninvasive index to assess liver involvement in children and adolescents with Wilson's disease (WD). METHODS: Children and adolescents diagnosed with WD were retrospectively collected from the First Affiliated Hospital of the Anhui University of Traditional Chinese Medicine between May 2022 and August 2022. The findings on ATT, Shear Wave Measurement (SWM), AST to platelet ratio index (APRI), and fibrosis 4 (FIB-4) score were obtained. The liver involvement of WD was classified into 3 groups based on serum levels of collagen type IV (CIV), hyaluronic acid (HA), laminin (LN) and precollagen type III N-terminal peptide (PIIINP): (1) Group1 (n = 25), no abnormalities in CIV, HA, LN and PIIINP; (2) Group2 (n = 19), elevation of 1 or 2 indexes in CIV, HA, LN, and PIIINP; Group3 (n = 18), elevation of 3 or 4 indicators in CIV, HA, LN, and PIIINP. The levels of ATT, SWM, APRI and FIB-4 were compared between the 3 groups; and correlation of ATT with SWM and triglyceride (TG) was performed using Spearman's correlation analysis. The Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of ATT alone and its combination with SWM, APRI, and FIB-4 in children and adolescents with WD. RESULTS: A total of 62 children and adolescents with WD were retrospectively retrieved. ATT levels were significantly different in intergroup comparisons (P < 0.001). The ROC curve showed that the area under the curve (AUC) for the diagnosis of hepatic steatosis using ATT was 0.714, 0.712 and 0.867 in Group 1 versus Group 2, Group 2 versus Group 3, and Group 1 versus Group 3, respectively; the sensitivity for the diagnosis of hepatic steatosis in Group 1 versus Group 2 was 89.47% with the cutoff value of ATT of 0.73 dB/cm/MHz. No significant correlation found between ATT and TG (ρ = 0.154, P = 0.231). Compared to ATT alone, the combination of ATT with APRI and FIB-4 or the combination of ATT with SWM, APRI, and FIB-4 showed a better diagnostic efficacy in Group 1 versus Group 2 (both P = 0.038). CONCLUSION: ATT could be used as a non-invasive index for the evaluation of liver steatosis in children and adolescents with WD, with a good clinical applicative value. Furthermore, ATT in combination with APRI, FIB-4, and SWM might have better diagnostic efficacy than ATT alone.

Altered microstructural pattern of the cortex and basal forebrain cholinergic system in wilson's disease: an automated fiber quantification tractography study.

Basal forebrain (BF) cholinergic projection neurons form a highly extensive input to the cortex. Failure of BF cholinergic circuits is responsible for the cognitive impairment associated with Wilson's disease (WD), but whether and how the microstructural changes in fiber projections between the BF and cerebral cortex influence prospective memory (PM) remain poorly understood. We collected diffusion tensor imaging (DTI) data from 21 neurological WD individuals and 26 healthy controls (HCs). The experiment reconstructed the probabilistic streamlined tractography of 18 white matter tracts using an automated fiber quantification (AFQ) toolkit. Tract properties (FA, MD, RD, and AD) were computed for 100 points along each tract for each participant, and the differences between the groups were examined. Subsequently, correlation analysis was performed to evaluate whether abnormal microstructural white matter integrity measures correlate with PM performance. Additional investigations used a tract-based spatial statistics (TBSS) approach to identify regions with altered white matter structure between groups and verify the reliability of the AFQ results. The highest nonoverlapping DTI-related differences were detected in the anterior thalamic radiation (ATR), corticospinal tract (CST), corpus callosum, association fibers, and limbic system fibers. Additionally, PM parameters of the patient group were highly correlated with white matter microstructure changes in the inferior longitudinal fasciculus. Our study highlights that the performance of projections between cholinergic input and output areas-the cerebral cortex and BF-may serve as neural biomarkers of PM and disease prognosis.

Free water imaging as a novel biomarker in Wilson's disease: A cross-sectional study.

BACKGROUND: The bi-tensor free water imaging may provide more specific information in detecting microstructural brain tissue alterations than conventional single tensor diffusion tensor imaging. The study aimed to investigate microstructural changes in deep gray matter (DGM) nuclei of Wilson's disease (WD) using a bi-tensor free water imaging and whether the findings correlate with the neurological impairment in WD patients. METHODS: The study included 29 WD patients and 25 controls. Free water and free water corrected fractional anisotropy (FAT) in DGM nuclei of WD patients were calculated. The correlations of free water and FAT with the Unified WD Rating Scale (UWDRS) neurological subscale of WD patients were performed. RESULTS: Free water and FAT values were significantly increased in multiple DGM nuclei of neurological WD patients compared to controls. WD patients with normal appearing on conventional MRI also had significantly higher free water and FAT values in multiple DGM nuclei than controls. Positive correlations were noted between the UWDRS neurological subscores and free water values of the putamen and pontine tegmentum as well as FAT values of the dentate nucleus, red nucleus, and globus pallidus. In addition, the measured free water and FAT values of specific structures also showed a positive correlation with specific clinical symptoms in neurological WD patients, such as dysarthria, parkinsonian signs, tremor, dystonia, and ataxia. CONCLUSIONS: Free water imaging detects microstructural changes in both normal and abnormal appearing DGM nuclei of WD patients. Free water imaging indices were correlated with the severity of neurological impairment in WD patients.

Lesions in White Matter in Wilson's Disease and Correlation with Clinical Characteristics.

BACKGROUND: Neuroimaging studies in Wilson's disease (WD) have identified various alterations in white matter (WM) microstructural organization. However, it remains unclear whether these alterations are localized to specific regions of fiber tracts, and what diagnostic value they might have. The purpose of this study is to explore the spatial profile of WM abnormalities along defined fiber tracts in WD and its clinical relevance. METHODS: Ninety-nine patients with WD (62 men and 37 women) and 91 age- and sex-matched controls (59 men and 32 women) were recruited to take part in experiments of diffusion-weighted imaging with 64 gradient vectors. The data were calculated by FMRIB Software Library (FSL) software and Automated Fiber Quantification (AFQ) software. After registration, patient groups and normal groups were compared by Mann-Whitney U test analysis. RESULTS: Compared with the controls, the patients with WD showed widespread fractional anisotropy reduction and mean diffusivity, radial diffusivity elevation of identified fiber tracts. Significant correlations between diffusion tensor imaging (DTI) parameters and the neurological Unified Wilson's Disease Rating Scale (UWDRS-N), serum ceruloplasmin, and 24-h urinary copper excretion were found. CONCLUSIONS: The present study has provided evidence that the metrics of DTI could be utilized as a potential biomarker of neuropathological symptoms in WD. Damage to the microstructure of callosum forceps and corticospinal tract may be involved in the pathophysiological process of neurological symptoms in WD patients, such as gait and balance disturbances, involuntary movements, dysphagia, and autonomic dysfunction.

Serum neurofilament light chain and initial severity of neurological disease predict the early neurological deterioration in Wilson's disease.

BACKGROUND: In Wilson's disease (WD), early neurological deterioration after treatment initiation is associated with poor outcomes; however, data on this phenomenon are limited. Our study analysed the frequency and risk factors of early neurological deterioration in WD. METHODS: Early neurological deterioration, within 6 months from diagnosis, was defined based on the Unified Wilson's Disease Rating Scale (UWDRS): any increase in part II or an increase of ≥ 4 in part III. In total, 61 newly diagnosed WD patients were included. UWDRS scores, brain magnetic resonance imaging (MRI) scores, copper metabolism parameters, treatment type and serum neuro-filament light chain (sNfL) concentrations at diagnosis were analysed as potential risk factors of early deterioration. RESULTS: Early neurological deterioration was observed in 16.3% of all WD patients; all cases of worsening occurred in the neurological phenotype (27.7%). Higher scores were seen in those who deteriorated compared with those who did not for UWDRS part II (4.3 ± 5.0 vs 2.0 ± 5.9; p < 0.05), UWDRS part III (21.5 ± 14.1 vs 9.3 ± 16.4; p < 0.01) and MRI-assessed chronic damage (3.2 ± 1.6 vs 1.4 ± 2.2; p = 0.006); all these variables indicated the initial severity of neurological disease. Pre-treatment sNfL concentrations were significantly higher in patients who deteriorated compared with those who did not (33.2 ± 23.5 vs 27.6 ± 62.7 pg/mL; p < 0.01). In univariate logistic regression amongst all patients, chronic damage MRI scores, UWDRS part III scores and sNfL concentrations predicated early deterioration. In the neurological WD, only sNFL were a significant predictor. In bivariate logistic regression amongst all patients, sNfL remained the only significant predictor of deterioration when corrected for MRI scores. CONCLUSION: sNfL concentrations are a promising biomarker of the risk of early neurological deterioration in WD.

[Nuclear medicine diagnostics in Wilson's disease]. / Nuklearmedizinische Diagnostik beim Morbus Wilson.

Wilson's disease is an autosomal recessive disorder of copper metabolism and is caused by a genetic defect on chromosome 13. Nuclear medicine methods can prove the metabolic defect and contribute to the assessment of central neurological deficits.With high specificity and sensitivity, the intravenous radiocopper test enables the diagnosis to be confirmed as the basis for initiating treatment. The oral radiocopper test is used to monitor zinc treatment.[123I]ß-CIT-SPECT and [123I]IBZM-SPECT provide functional information of the nigrostriatal system.[123I]ß-CIT-SPECT also allows the determination of SERT availability in the hypothalamus/brain stem as a surrogate parameter of depression.Metabolic parameters of the cortex, basal ganglia and cerebellum can be assessed by [18F]FDG-PET studies.SPECT and [18F]FDG-PET studies show significant differences between neurological and non-neurological Wilson patients. Overall, only noninvasive in vivo nuclear medicine enables a deeper insight into the pathophysiology of neurological processes in Wilson's disease.