Pathognomonic neuroradiological signs in Wilson's disease - Truth or myth?

INTRODUCTION: Wilson's disease (WD) is a treatable genetic disorder caused by impaired copper metabolism. Early diagnosis and correct anti-copper treatment are crucial for therapeutic success. Brain magnetic resonance imaging (MRI) is used both for diagnosis and treatment monitoring. Several neuroradiological signs have been proposed to be pathognomonic for WD; however, their frequency and significance are not established. The frequency and significance of these brain MRI signs were analyzed in a large cohort of WD patients. METHODS: We retrospectively analyzed 100 newly diagnosed, treatment-naive WD patients. Brain MRI was performed and the frequency of typical MRI changes was analyzed with demographic, clinical and laboratory characteristics of WD. RESULTS: Potentially pathognomonic brain MRI signs for WD occurred in 24% patients and in 43% (24/55) patients with neurological WD. Signs detected included the "face of the giant panda" in 15% of all patients (27.3% of neurological cases), "miniature panda" in 12% (21.8% of neurological cases), "split thalamus" in 7% (12.7% of neurological cases), and "bright claustrum" and "whorl" signs in 1 patients each. Signs were observed only in patients with neurological symptoms and were significantly associated with early age of onset/diagnosis, more severe neurological presentation and lower ceruloplasmin level (all p < 0.05). CONCLUSIONS: Potentially brain MRI pathognomonic signs occurred relatively rarely across all patients, most often in patients with early onset and severe neurological symptoms, and this knowledge may improve WD diagnosis. However, as these signs are also found in brain MRI in other disorders, they may not be truly pathognomonic of WD.

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.

Brain magnetic resonance imaging and severity of neurological disease in Wilson's disease - the neuroradiological correlations.

INTRODUCTION: Wilson's disease (WD) is a genetic disorder with pathological copper accumulation and associated clinical symptoms in various organs, particularly the liver and brain. Neurological disease is assessed with the clinical Unified Wilson's Disease Rating Scale (UWDRS). There is a lack of quantitative objective markers evaluating brain involvement. Recently, a semiquantitative brain magnetic resonance imaging (MRI) scale has been proposed, which combines acute toxicity and chronic damage measures into a total score. The relationship between MRI brain pathology and the MRI scale with disease form and neurological severity was studied in a large cohort. METHODS: We retrospectively assessed 100 newly diagnosed treatment-naïve patients with WD with respect to brain MRI pathology and MRI scores (acute toxicity, chronic damage, and total) and analyzed the relationship with disease form and UWDRS part II (functional impairment) and part III (neurological deficits) scores. RESULTS: Most patients had the neurological form of WD (55%) followed by hepatic (31%) and presymptomatic (14%). MRI examination revealed WD-typical abnormalities in 56% of patients, with higher pathology rates in neurological cases (83%) than in hepatic (29%) and presymptomatic (7%) cases. UWDRS part II and III scores correlated with the MRI acute toxicity score (r = 0.55 and 0.55, respectively), chronic damage score (r = 0.39 and 0.45), and total score (0.45 and 0.52) (all P < 0.01). CONCLUSIONS: Brain MRI changes may be present even in patients without neurological symptoms, although not frequently. The semiquantitative MRI scale correlated with the UWDRS and appears to be a complementary tool for severity of brain injury assessment in WD patients.

Semiquantitative Scale for Assessing Brain MRI Abnormalities in Wilson Disease: A Validation Study.

BACKGROUND: MRI is a sensitive method for the assessment of brain abnormalities in Wilson disease, that is, T2 hyperintensities, T2 hypointensities, and atrophy, but a validated scoring system for the classification of radiological severity is lacking. The objective of this study was to develop and validate a brain MRI visual rating scale for Wilson disease. METHODS: The proposed Wilson disease brain MRI severity scale consists of acute toxicity and chronic damage subscores from predefined structures. The former, calculated by summing scores of T2 hyperintensities (excluding cavitation), is likely to be partially reversible with treatment. The latter, representing the sum of scores of T2 hypointensities and brain atrophy, reflects pathology that is not readily reversible. Validation was performed on MRI scans acquired using 1.5T system from 39 Wilson disease patients examined at baseline and after 24 months on anticopper treatment. Intraclass correlation coefficients of 5 ratings from 3 raters were calculated. Temporal evolution of the MRI severity score and its association with clinical severity, assessed using the Unified Wilson Disease Rating Scale part III, was calculated. RESULTS: Intrarater and interrater agreement were good (r > 0.93; P < 0.001; and r > 0.74; P < 0.001, respectively). In neurologic Wilson disease patients, the total MRI severity score improved over 2 years (P = 0.032), mainly because of reduced acute toxicity (P = 0.0015), whereas the chronic damage score deteriorated (P = 0.035). Unified Wilson Disease Rating Scale part III score was positively associated with chronic damage and total score at baseline (P = 0.005 and P = 0.003, respectively) and in month 24 (P < 0.001 and P = 0.001, respectively). CONCLUSIONS: The Wilson disease brain MRI severity scale is a simple, reliable, and valid instrument that allows semiquantitative assessment of radiological Wilson disease severity. © 2020 International Parkinson and Movement Disorder Society.

Brain volume is related to neurological impairment and to copper overload in Wilson's disease.

INTRODUCTION: To determine whether brain volume was associated with functional and neurological impairments and with copper overload markers in patients with Wilson's disease. METHODS: In 48 treatment-naïve patients, we assessed functional and neurological impairments with the Unified Wilson's Disease Rating Scale, measured normalized brain volumes based on magnetic resonance images, and assessed concentration of non-ceruloplasmin-bound copper. We correlated brain volume measures with functional and neurological impairment scores and copper overload indices. RESULTS: Functional and neurological impairments correlated with all brain volume measures, including the total brain volume and the volumes of white matter and gray matter (both peripheral gray matter and deep brain nuclei). Higher non-ceruloplasmin-bound copper concentrations were associated with greater functional and neurological impairments and lower brain volumes. CONCLUSIONS: Our findings provided the first in vivo evidence that the severity of brain atrophy is a correlate of functional and neurological impairments in patients with Wilson's disease and that brain volume could serve as a marker of neurodegeneration induced by copper.