BackgroundMRI 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.MethodsThe 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.ResultsIntrarater 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).ConclusionsThe 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

Discontinuation of fingolimod in patients with multiple sclerosis (MS) can lead to disease reactivation. In this review, we describe cases of severe exacerbations in patients with MS following discontinuation of fingolimod, including three cases from our center. We consider potential mechanisms of disease reactivation after cessation of fingolimod, and the evidence supporting this rebound effect. We conclude that discontinuation of fingolimod results in the return of disease activity, which then leads to severe exacerbations (i.e., rebounds) in a clinically significant proportion of patients. Lastly, we consider disease-modifying treatment options for patients who discontinue fingolimod.

IntroductionTo determine whether brain volume was associated with functional and neurological impairments and with copper overload markers in patients with Wilson’s disease.MethodsIn 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.ResultsFunctional 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (10.1007/s10072-019-03942-z) contains supplementary material, which is available to authorized users.

The radioactive copper test had excellent diagnostic accuracy and may be useful in the evaluation of new therapies aimed at restoring ATP7B function.

Small-caliber cerebral vessels change their diameters in response to alterations of key metabolite concentrations such as carbon dioxide or oxygen. This phenomenon, termed the cerebral vasomotor reactivity (CVMR), is the basis for blood flow regulation in the brain in accordance with its metabolic status. Typically, CVMR is determined as the amount of change in cerebral blood flow in response to a vasodilating stimulus, which can be measured by various neuroimaging methods or by transcranial Doppler. It has been shown that CVMR is impaired in cerebrovascular diseases, but there is also evidence of a similar dysfunction in neurodegenerative disorders. Here, we review studies that have investigated CVMR in the common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. Moreover, we discuss potential neurodegenerative mechanisms responsible for the impairment of CVMR.