Cerebellar contribution to motor and cognitive impairment in multiple sclerosis patients: a sub-regional structural MRI analysis
Elisabetta Pagani1, Maria Assunta Rocca1,2, Alessandro D'Ambrosio1,3, Gianna Carla Riccitelli1, Bruno Colombo2, Mariaemma Rodegher2, Andrea Falini4, Giancarlo Comi2, and Massimo Filippi1,2

1Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 2Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 3I Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy, 4Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

Synopsis

Aim of the study was to assess the role of cerebellar global and sub-regional involvement on motor and cognitive impairment in multiple sclerosis (MS) patients. Cerebellar segmentation and lobular parcellation was performed on T1 weighted images from 95 MS patients and 32 healthy controls using SUIT tool. The Nine Hole Peg Test was obtained as a measure of motor performance; patients also underwent cognitive evaluation. Cerebellar posterior-inferior volume accounted for variance in cognitive measures in MS patients, whereas anterior cerebellar volume accounted for variance in motor performance, supporting a critical contribution of regional cerebellar damage to clinical manifestations of MS.

Background

The cerebellum plays a role in a wide variety of complex behaviors. Many evidences support a topographic division into “motor” and “non-motor” regions mapped to the anterior and posterior lobe of the cerebellum, respectively (1). Currently, no study has investigated the impact of structural cerebellar sub-regional involvement on motor and cognitive manifestations in multiple sclerosis (MS) patients.

Purpose

To assess the role of cerebellar global and sub-regional involvement on motor and cognitive performance in MS patients.

Methods

Cerebellar segmentation and lobular parcellation was performed on high resolution 3D T1 weighted brain images from 95 MS patients (53 relapsing remitting [RR] MS, 20 benign MS and 22 secondary progressive [SP] MS) and 32 healthy controls (HC) using the SUIT tool (2) from SPM12. For all subjects, the Nine Hole Peg Test (9-HPT) was obtained as a measure of motor performance. MS patients also underwent cognitive evaluation, including the Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT) and Wisconsin Card Sorting Test (WCST). The SUIT tool automatically isolates the cerebellum, which is then non-linearly transformed with Dartel (3) onto the standard space. A probabilistic atlas is available, based on the anatomy of 20 healthy subjects, whose lobules were segmented according to Schmahmann et al. (4). Through the application of the atlas, the volumes of the anterior and posterior regions were obtained, after combining lobules I-V and VI-X respectively (Figure 1). Volumes were then normalized for the intracranial volume. Spearman’s correlations between normalized cerebellar volumes vs motor and cognitive scores were estimated (p<0.05).

Results

Global and regional cerebellar volumes did not differ between MS patients and HC. In MS patients, better 9-HPT performance correlated with higher global and regional cerebellar volumes, with stronger correlation with the anterior regions (lobules I-V) (p=0.02, r=0.24) (Figure 2). In RRMS patients, better cognitive performance (SDMT, WCST) correlated with higher global and posterior-inferior (lobules VI-X) cerebellar volumes (p range: 0.008-0.01, r range: 0.30-0-32) (Figure 3).

Conclusions

Cerebellar posterior-inferior volume accounted for variance in cognitive measures in MS patients, whereas anterior cerebellar volume accounted for variance in motor performance, supporting a critical contribution of regional cerebellar damage to the clinical manifestations of MS.

Acknowledgements

This study has been partially supported by a grant from FISM 2011/R/19 and Italian Ministry of Health (GR-2009-1529671).

References

1) Stoodley CJ, Valera EM, Schmahmann JD. Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study. Neuroimage. 2012;59(2):1560-70.

2) Diedrichsen J, Balster J.H., Flavell J, Cussans E, Ramnani N. A probabilistic MR atlas of the human cerebellum. Neuroimage. 2009;46(1):39-46.

3) Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage. 2007;38(1):95-113.

4) Schmahmann JD, Doyon J, McDonald D, Holmes C, Lavoie K, Hurwitz AS, Kabani N, Toga A, Evans A, Petrides M. Three-dimensional MRI atlas of the human cerebellum in proportional stereotaxic space. Neuroimage. 1999;10(3 Pt 1):233-60.

Figures

Figure 1. T1 weighted scan of a representative MS patient. The image was transformed into the atlas space and the SUIT atlas was overlapped. The different colours show the lobular parcellation (first row). According to Stoodley et al., lobules were merged to obtained the anterior (red) and the posterior (blue) region of the cerebellum (second row).

Figure 2. Correlation scatterplot of the whole MS group. The normalized volumes of the anterior cerebellar regions are plot against the left-right averaged inverted 9-HPT score.

Figure 3. Correlation scatterplot of the RRMS group. The normalized volumes of the posterior cerebellar regions are plot against the SDMT score.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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