Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine

Performance of two real-life California bridges under regional natural hazards

The performance of two real-life California bridges is assessed under a possible regional multihazard condition involving floods and earthquakes. For flood events with varied frequency, expected scour depths at bridge piers are calculated and incorporated in finite-element analyses (FEAs) of the bridges under earthquakes that represent regional seismic hazards. Based on FEA results, fragility curves of bridges are developed at component and system levels. Fragility surfaces are generated to acquire comprehensive knowledge on bridge failure probability for the combined effect of earthquake and flood events of varying frequency. Quantified bridge vulnerability is applied to a risk evaluation framework that combines hazard probability with bridge failure consequences. Obtained results depict that the occurrence of flood events can increase the seismic vulnerability and risk of bridges, although the amount of increase depends on bridge attributes. Bigger (large-diameter) foundations tend to reduce the impact of flood hazard on bridge seismic performance. Moreover, the multihazard response of the bridges indicates that the seismic design philosophy used for bridges can play a role in attaining the seismic safety of bridges with flood-induced scour at the foundations.NS

Lesion location alters brain activation in chronically impaired stroke survivors

Recovery of motor function after stroke is associated with reorganization in central motor networks. Functional imaging has demonstrated recovery-dependent alterations in brain activation patterns when compared to healthy controls. These alterations are variable across stroke subjects. Factors identified as contributing to this variability are the degree of functional impairment, the time interval since stroke, and rehabilitative therapies. Here, the hypothesis is tested that lesion location influences the activation patterns. Using functional magnetic resonance imaging, the objective was to characterize similarities or differences in movement-related activation patterns in patients chronically disabled by cortical plus subcortical or subcortical lesions only. Brain activation was mapped during paretic and non-paretic movement in 11 patients with subcortical stroke, in nine patients with stroke involving sensorimotor cortex, and in eight healthy volunteers. Patient groups had similar average motor deficit as measured by a battery of scores and strength measures. Substantial differences between patients groups were found in activation patterns associated with paretic limb movement: Whereas contralateral motor cortex, ipsilateral cerebellum (relative to moving limb), bilateral mesial (cingulate, SMA), and perisylvian regions were active in subcortical stroke, cortical patients recruited only ipsilateral postcentral mesial hemisphere regions, and areas at the rim of the stroke cavity. For both groups, activation in ipsilateral postcentral cortex correlated with motor function; in subcortical stroke, the same was found for mesial and perisylvian regions. Overall, brain activation in cortical stroke was less, while in subcortical patients, more than in healthy controls. For non-paretic movement, activation patterns were similar to control in cortical patients. In subcortical patients, however, activation patterns differed: the activation of non-paretic movement was similar to that of paretic movement (corrected for side). The data demonstrate more differences than similarities in the central control of paretic and non-paretic limb movement in patients chronically disabled by subcortical versus cortical stroke. Whereas standard motor circuitry is utilized in subcortical stroke, alternative networks are recruited after cortical stroke. This finding proposes lesion-specific mechanisms of reorganization. Optimal activation of these distinct networks may require different rehabilitative strategie

Repetitive bilateral arm training and motor cortex activation in chronic stroke

Context: reorganization in central motor networks occurs during early recovery from hemiparetic stroke. In chronic stroke survivors, specific rehabilitation therapy can improve upper extremity function.Objective: to test the hypothesis that in patients who have chronic motor impairment following stroke, specific rehabilitation therapy that improves arm function is associated with reorganization of cortical networks.Design, setting, and patients: a randomized controlled clinical trial conducted in a US ambulatory rehabilitation program with 21 patients (median [IQR], 50.3 [34.8-77.3] months after unilateral stroke). Data were collected between 2001 and 2004.Interventions: patients were randomly assigned to bilateral arm training with rhythmic auditory cueing (BATRAC) (n = 9) or standardized dose-matched therapeutic exercises (DMTE) (n = 12). Both were conducted for 1 hour, 3 times a week, for 6 weeks.Main outcome measures: within 2 weeks before and after the intervention, brain activation during elbow movement assessed by functional magnetic resonance imaging (fMRI) and functional outcome assessed using arm function scores.Results: patients in the BATRAC group but not in the DMTE group increased hemispheric activation during paretic arm movement (P = .03). Changes in activation were observed in the contralesional cerebrum and ipsilesional cerebellum (P = .009). BATRAC was associated with significant increases in activation in precentral (P < .001) and postcentral gyri (P = .03) and the cerebellum (P < .001), although 3 BATRAC patients showed no fMRI changes. Considering all patients, there were no differences in functional outcome between groups. When only BATRAC patients with fMRI response were included (n = 6), BATRAC improved arm function more than DMTE did (P = .02).Conclusions: these preliminary findings suggest that BATRAC induces reorganization in contralesional motor networks and provide biological plausibility for repetitive bilateral training as a potential therapy for upper extremity rehabilitation in hemiparetic strok

Na+ deposition in the fibrotic skin of systemic sclerosis patients detected by 23Na-magnetic resonance imaging

Objective. Skin fibrosis is the predominant feature of SSc and arises from excessive extracellular matrix deposition. Glycosaminoglycans are macromolecules of the extracellular matrix, which facilitate Na+ accumulation in the skin. We used Na-23-MRI to quantify Na+ in skin. We hypothesized that skin Na+ might accumulate in SSc and might be a biomarker for skin fibrosis. Methods. In this observational case-control study, skin Na+ was determined by Na-23-MRI using a Na+ volume coil in 12 patients with diffuse cutaneous SSc and in 21 control subjects. We assessed skin fibrosis by the modified Rodnan skin score prior to Na-23-MRI and on follow-up 12 months later. Results.Na-23-MRI demonstrated increased Na+ in the fibrotic skin of SSc patients compared with skin from controls [mean (s.d.): 27.2 (5.6) vs 21.4 (5.3) mmol/l, P < 0.01]. Na+ content was higher in fibrotic than in non-fibrotic SSc skin [26.2 (4.8) vs 19.2 (3.4) mmol/l, P < 0.01]. Furthermore, skin Na+ amount was correlated with changes in follow-up modified Rodnan skin score (R-2 = 0.68). Conclusions.Na-23-MRI detected increased Na+ in the fibrotic SSc skin; high Na+ content was associated with progressive skin disease. Our findings provide the first evidence that Na-23-MRI might be a promising tool to assess skin Na+ and thereby predict progression of skin fibrosis in SSc

Graft-versus-Host Erkrankung, chronisch

Die chronische Graft-versus-Host-Erkrankung (GvHD) ist eine protrahiert einsetzende Reaktion des Spenderimmunsystems gegen Gewebe des Empfängers. Sie tritt bei ca. 50% der Patient*innen nach allogener hämatopoetischer Stammzelltransplantation und in der Regel nach 2 bis 18 Monaten erstmalig auf. Für die Diagnose muss eine eindeutige klinische Symptomatik/Manifestation oder eine histolo­ gische Sicherung vorliegen. Die Therapie richtet sich nach dem Schweregrad der chronischen GvHD und der Organmanifes­ tation. Sie besteht aus topischen Maßnahmen, systemischer Gabe von Kortikosteroiden, ggf. in Kombination mit weiteren Immunsuppressiva. Insbesondere die schwere chronischen GvHD ist für ca. 25% der Todesfälle nach allogener hämatopoetischer Stammzelltransplantation mit verantwortlich