Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis
Abstract
Objective:
While the hallmark of amyotrophic lateral sclerosis (ALS) is corticospinal tract in combination with lower motor neuron degeneration, the clinical involvement of both compartments is characteristically variable and the site of onset debated. We sought to establish whether there is a consistent signature of cerebral white matter abnormalities in heterogeneous ALS cases.
Methods:
In this observational study, diffusion tensor imaging was applied in a whole-brain analysis of 24 heterogeneous patients with ALS and well-matched healthy controls. Tract-based spatial statistics were used, with optimized voxel-based morphometry of T1 images to determine any associated gray matter involvement.
Results:
A consistent reduction in fractional anisotropy was demonstrated in the corpus callosum of the ALS group, extending rostrally and bilaterally to the region of the primary motor cortices, independent of the degree of clinical upper motor neuron involvement. Matched regional radial diffusivity increase supported the concept of anterograde degeneration of callosal fibers observed pathologically. Gray matter reductions were observed bilaterally in primary motor and supplementary motor regions, and also in the anterior cingulate and temporal lobe regions. A post hoc group comparison model incorporating significant values for fractional anisotropy, radial diffusivity, and gray matter was 92% sensitive, 88% specific, with an accuracy of 90%.
Conclusion:
Callosal involvement is a consistent feature of ALS, independent of clinical upper motor neuron involvement, and may reflect independent bilateral cortical involvement or interhemispheric spread of pathology. The predominantly rostral corticospinal tract involvement further supports the concept of independent cortical degeneration even in those patients with ALS with predominantly lower motor neuron involvement clinically.
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REFERENCES
1.
Rothstein JD. Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann Neurol 2009;65(suppl 1):S3–S9.
2.
Turner MR, Kiernan MC, Leigh PN, Talbot K. Biomarkers in amyotrophic lateral sclerosis. Lancet Neurol 2009;8:94–109.
3.
Johansen-Berg H, Behrens TE. Diffusion MRI: From Quantitative Measurement to in-vivo Neuroanatomy. Academic Press; 2009.
4.
Turner MR, Cagnin A, Turkheimer FE, et al. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [(11)C](R)-PK11195 positron emission tomography study. Neurobiol Dis 2004;15:601–609.
5.
Smith MC. Nerve fibre degeneration in the brain in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 1960;23:269–282.
6.
Ellis CM, Simmons A, Jones DK, et al. Diffusion tensor MRI assesses corticospinal tract damage in ALS. Neurology 1999;53:1051–1058.
7.
Wong JC, Concha L, Beaulieu C, Johnston W, Allen PS, Kalra S. Spatial profiling of the corticospinal tract in amyotrophic lateral sclerosis using diffusion tensor imaging. J Neuroimaging 2007;17:234–240.
8.
Roccatagliata L, Bonzano L, Mancardi G, Canepa C, Caponnetto C. Detection of motor cortex thinning and corticospinal tract involvement by quantitative MRI in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2009;10:47–52.
9.
Iwata NK, Aoki S, Okabe S, et al. Evaluation of corticospinal tracts in ALS with diffusion tensor MRI and brainstem stimulation. Neurology 2008;70:528–532.
10.
Hong YH, Lee KW, Sung JJ, Chang KH, Song IC. Diffusion tensor MRI as a diagnostic tool of upper motor neuron involvement in amyotrophic lateral sclerosis. J Neurol Sci 2004;227:73–78.
11.
Chou SM, Norris FH. Amyotrophic lateral sclerosis: lower motor neuron disease spreading to upper motor neurons. Muscle Nerve 1993;16:864–869.
12.
Eisen A, Kim S, Pant B. Amyotrophic lateral sclerosis (ALS): a phylogenetic disease of the corticomotoneuron? Muscle Nerve 1992;15:219–224.
13.
Ravits JM, La Spada AR. ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration. Neurology 2009;73:805–811.
14.
Sage CA, Van Hecke W, Peeters R, et al. Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis: revisited. Hum Brain Mapp 2009;30:3657–3675.
15.
Sage CA, Peeters RR, Gorner A, Robberecht W, Sunaert S. Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis. Neuroimage 2007;34:486–499.
16.
Sach M, Winkler G, Glauche V, et al. Diffusion tensor MRI of early upper motor neuron involvement in amyotrophic lateral sclerosis. Brain 2004;127:340–350.
17.
Senda J, Ito M, Watanabe H, et al. Correlation between pyramidal tract degeneration and widespread white matter involvement in amyotrophic lateral sclerosis: a study with tractography and diffusion-tensor imaging. Amyotroph Lateral Scler 2009;10:288–294.
18.
Agosta F, Pagani E, Rocca MA, et al. Voxel-based morphometry study of brain volumetry and diffusivity in amyotrophic lateral sclerosis patients with mild disability. Hum Brain Mapp 2007;28:1430–1438.
19.
Chao YP, Cho KH, Yeh CH, Chou KH, Chen JH, Lin CP. Probabilistic topography of human corpus callosum using cytoarchitectural parcellation and high angular resolution diffusion imaging tractography. Hum Brain Mapp 2009;30:3172–3187.
20.
Ciccarelli O, Behrens TE, Johansen-Berg H, et al. Investigation of white matter pathology in ALS and PLS using tract-based spatial statistics. Hum Brain Mapp 2009;30:615–624.
21.
Unrath A, Muller HP, Riecker A, Ludolph AC, Sperfeld AD, Kassubek J. Whole brain-based analysis of regional white matter tract alterations in rare motor neuron diseases by diffusion tensor imaging. Hum Brain Mapp 2010 (in press).
22.
Karandreas N, Papadopoulou M, Kokotis P, Papapostolou A, Tsivgoulis G, Zambelis T. Impaired interhemispheric inhibition in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2007;8:112–118.
23.
Bartels C, Mertens N, Hofer S, et al. Callosal dysfunction in amyotrophic lateral sclerosis correlates with diffusion tensor imaging of the central motor system. Neuromuscul Disord 2008;18:398–407.
24.
Wittstock M, Wolters A, Benecke R. Transcallosal inhibition in amyotrophic lateral sclerosis. Clin Neurophysiol 2007;118:301–307.
25.
Vucic S, Nicholson GA, Kiernan MC. Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis. Brain 2008;131:1540–1550.
26.
Aggarwal A, Nicholson G. Detection of preclinical motor neurone loss in SOD1 mutation carriers using motor unit number estimation. J Neurol Neurosurg Psychiatry 2002;73:199–201.
27.
Ellis CM, Suckling J, Amaro E, et al. Volumetric analysis reveals corticospinal tract degeneration and extramotor involvement in ALS. Neurology 2001;57:1571–1578.
28.
Cosottini M, Giannelli M, Siciliano G, et al. Diffusion-tensor MR imaging of corticospinal tract in amyotrophic lateral sclerosis and progressive muscular atrophy. Radiology 2005;237:258–264.
29.
Concha L, Gross DW, Wheatley BM, Beaulieu C. Diffusion tensor imaging of time-dependent axonal and myelin degradation after corpus callosotomy in epilepsy patients. Neuroimage 2006;32:1090–1099.
30.
Eisen A. Amyotrophic lateral sclerosis: evolutionary and other perspectives. Muscle Nerve 2009;40:297–304.
31.
Turner MR, Wicks P, Brownstein CA, et al. Concordance between site of onset and limb dominance in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2010 (in press).
32.
Matsuo K, Mizuno T, Yamada K, et al. Cerebral white matter damage in frontotemporal dementia assessed by diffusion tensor tractography. Neuroradiology 2008;50:605–611.
33.
Gredal O, Pakkenberg H, Karlsborg M, Pakkenberg B. Unchanged total number of neurons in motor cortex and neocortex in amyotrophic lateral sclerosis: a stereological study. J Neurosci Methods 2000;95:171–176.
34.
Kassubek J, Unrath A, Huppertz HJ, et al. Global brain atrophy and corticospinal tract alterations in ALS, as investigated by voxel-based morphometry of 3-D MRI. Amyotroph Lateral Scler Other Motor Neuron Disord 2005;6:213–220.
35.
Chang JL, Lomen-Hoerth C, Murphy J, et al. A voxel-based morphometry study of patterns of brain atrophy in ALS and ALS/FTLD. Neurology 2005;65:75–80.
36.
Grosskreutz J, Kaufmann J, Fradrich J, Dengler R, Heinze HJ, Peschel T. Widespread sensorimotor and frontal cortical atrophy in amyotrophic lateral sclerosis. BMC Neurol 2006;6:17.
37.
Grosskreutz J, Peschel T, Unrath A, Dengler R, Ludolph AC, Kassubek J. Whole brain-based computerized neuroimaging in ALS and other motor neuron disorders. Amyotroph Lateral Scler 2008;9:238–248.
38.
Turner MR, Hammers A, Al Chalabi A, et al. Distinct cerebral lesions in sporadic and ‘D90A' SOD1 ALS: studies with [11C]flumazenil PET. Brain 2005;128:1323–1329.
39.
Ng MC, Ho JT, Ho SL, et al. Abnormal diffusion tensor in nonsymptomatic familial amyotrophic lateral sclerosis with a causative superoxide dismutase 1 mutation. J Magn Reson Imaging 2008;27:8–13.
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Copyright © 2010 by AAN Enterprises, Inc.
Publication History
Received: April 9, 2010
Accepted: June 21, 2010
Published online: November 1, 2010
Published in print: November 2, 2010
Disclosure
Dr. Filippini receives research support from the Gordon Small Charitable Trust. Dr. Douaud receives license fee and royalty payments from the University of Oxford for FSL software and receives research support from the Engineering and Physical Sciences Research Council (EPSRC). Dr. Mackay and S. Knight report no disclosures. Dr. Talbot serves on a scientific advisory board for Agenzia di Ricerca per la Sclerosi Laterale Amiotrofica (AriSLA); serves on the editorial board of Neuropathology and Applied Neurobiology; receives royalties from the publication of Medicine at a Glance (Blackwell Science, 2002), Motor Neuron Disease: The Facts (Oxford University Press, 2009), and Motor Neuron Disease: A Practical Manual (Oxford University Press, 2010); and receives research support from the Motor Neurone Disease Association and SMA Trust. Dr. Turner receives royalties from the publication of The Brain: A Beginner's Guide (Oneworld, 2008) and Motor Neuron Disease: A Practical Manual (Oxford University Press, 2010); serves as a consultant for Evalueserve, IMS Hospital Group Ltd., Smartanalyst Inc., Scisive, and Guidepoint Global; and receives research support from the Medical Research Council, the Motor Neurone Disease Association Lady Edith Wolfson Fellowship.
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