Relationship between Damage to the Cerebellar Peduncles and Clinical Disability in Multiple Sclerosis

Preziosa, Paolo; Rocca, Maria A.; Mesaroš, Šarlota; Pagani, Elisabetta; Drulović, Jelena; Stošić-Opinćal, Tatjana; Dačković, Jelena; Copetti, Massimiliano; Caputo, Domenico; Filippi, Massimo

doi:10.1148/radiol.13132142

Cited by 51 publications

(53 citation statements)

References 33 publications

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“…9, 33-35 We were actually impressed by the strength and high reproducibility of the developed models and how well the models selected those anatomical structures that underlie physical versus cognitive disability, 36-38 without any pre-existing knowledge of biology. This validates the MRI elements selected by mathematical models as biologically meaningful.…”

Section: Discussionmentioning

confidence: 99%

Novel composite MRI scale correlates highly with disability in multiple sclerosis patients

Kósa

Komori

Waters

et al. 2015

Multiple Sclerosis and Related Disorders

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Understanding genotype-phenotype relationships or development/validation of biomarkers requires large multicenter cohorts integrated by universal quantification of crucial phenotypical traits, such as central nervous system (CNS) tissue destruction. We hypothesized that mathematical modeling-guided combination of biologically meaningful, semiquantitative MRI elements characterized by high signal-to-noise ratio will provide such reliable, universal tool for measuring CNS tissue destruction. We retrospectively graded 15 elements in MRI scans performed in 419 untreated subjects with or without neurological diseases, while being blinded to their prospectively acquired clinical scores. We then used 305 subjects for disability-guided mathematical modeling to select and combine MRI elements that had non-redundant contributions to clinical disability, resulting in Combinatorial MRI Scale (COMRIS). We validated our model on the remaining 114 independent subjects. COMRIS requires 5-10 minutes per scan on average to compute and demonstrates highly significant (p<0.0001) and validation-consistent Spearman correlation coefficients (0.75, 0.76, and 0.65) for the expanded disability status scale (EDSS), Scripps neurological rating scale (SNRS), and symbol digit modality test (SDMT) measures of neurological disability, respectively. Because COMRIS is not greatly influenced by MRI scanners or protocols and can be computed even in the presence of some motion artifacts, it does not require censoring out patients and it provides comparable results across different cohorts. As such, it represents a broadly available clinical and research tool that can facilitate multicenter research studies and comparative analyses across patient cohorts and research projects.

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Section: Discussionmentioning

confidence: 99%

Novel composite MRI scale correlates highly with disability in multiple sclerosis patients

Kósa

Komori

Waters

et al. 2015

Multiple Sclerosis and Related Disorders

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“…Cerebellum volume loss in MS patients moderately correlated with motor disability [Anderson et al, ; Calabrese et al, ] and cognitive impairment [Weier et al, ], whereas volume loss in selected cerebellar lobes (IV, V, VI, and VIII) was associated with balance impairment [Prosperini et al, ]. Damage in cerebellar white matter tracts, as measured by diffusion MRI, was described in cohorts of MS patients, including both RRMS and SPMS, with different degrees of disability and cognitive impairment [Hulst et al, ; Preziosa et al, ]. Conversely, compensatory plasticity in cerebellar‐frontal lobe connections was evident in RRMS, but not at later disease stages (SPMS) [Rocca et al, ].…”

Section: Discussionmentioning

confidence: 99%

Multicontrast connectometry: A new tool to assess cerebellum alterations in early relapsing‐remitting multiple sclerosis

Romascano

Meskaldji

Bonnier

et al. 2014

Human Brain Mapping

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Background: Cerebellar pathology occurs in late multiple sclerosis (MS) but little is known about cerebellar changes during early disease stages. In this study, we propose a new multicontrast "connectometry" approach to assess the structural and functional integrity of cerebellar networks and connectivity in early MS. Methods: We used diffusion spectrum and resting-state functional MRI (rs-fMRI) to establish the structural and functional cerebellar connectomes in 28 early relapsing-remitting MS patients and 16 healthy controls (HC). We performed multicontrast "connectometry" by quantifying multiple MRI parameters along the structural tracts (generalized fractional anisotropy-GFA, T1/T2 relaxation times and magnetization transfer ratio) and functional connectivity measures. Subsequently, we assessed multivariate differences in local connections and network properties between MS and HC subjects; finally, we correlated detected alterations with lesion load, disease duration, and clinical scores. Results: In MS patients, a subset of structural connections showed quantitative MRI changes suggesting loss of axonal microstructure and integrity (increased T1 and decreased GFA, P < 0.05). These alterations highly correlated with motor, memory and attention in patients, but were independent of cerebellar lesion load and disease duration. Neither network organization nor rs-fMRI abnormalities were observed at this early stage. Conclusion: Multicontrast cerebellar connectometry revealed subtle cerebellar alterations in MS patients, which were independent of conventional disease markers and highly correlated with patient function. Future work should assess the prognostic value of the observed damage. Hum Brain Mapp 36:1609-1619, 2015. V C 2014 Wiley Periodicals, Inc.

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“…One study revealed abnormalities in tractography signals within the superior cerebellar peduncle, which correlated with upper limb dysfunction in patients with PPMS (36). Indeed, the presence of T2 lesions within cerebellar peduncles on MRI was associated with cerebellar and ambulatory symptoms in a large imaging study (37). As stated above, cerebellar gray matter disease may be extensive in pathological samples.…”

Section: Monitoring Cerebellar Disease In Msmentioning

confidence: 99%

Cerebellar Dysfunction in Multiple Sclerosis

Wilkins

2017

Front. Neurol.

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Multiple sclerosis (MS) commonly affects the cerebellum causing acute and chronic symptoms. Cerebellar signs contribute significantly to clinical disability, and symptoms such as tremor, ataxia, and dysarthria are particularly difficult to treat. Increasing knowledge concerning the pathophysiology of cerebellar disease in MS from human postmortem studies, experimental models, and clinical trials has raised the hope that cerebellar symptoms will be better treated in the future.

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Relationship between Damage to the Cerebellar Peduncles and Clinical Disability in Multiple Sclerosis

Abstract: The assessment of middle and superior cerebellar peduncle damage contributes to the explanation of cerebellar and/or brainstem symptoms and ambulatory impairment in MS.

Cited by 51 publications

References 33 publications

Novel composite MRI scale correlates highly with disability in multiple sclerosis patients

Novel composite MRI scale correlates highly with disability in multiple sclerosis patients

Multicontrast connectometry: A new tool to assess cerebellum alterations in early relapsing‐remitting multiple sclerosis

Cerebellar Dysfunction in Multiple Sclerosis

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