Diffusion tensor imaging of brain white matter in Huntington gene mutation individuals

ABSTRACT

Objective

To evaluate the role of the involvement of white matter tracts in huntingtin gene mutation patients as a potential biomarker of the progression of the disease.

Methods

We evaluated 34 participants (11 symptomatic huntingtin gene mutation, 12 presymptomatic huntingtin gene mutation, and 11 controls). We performed brain magnetic resonance imaging to assess white matter integrity using diffusion tensor imaging, with measurement of fractional anisotropy.

Results

We observed a significant decrease of fractional anisotropy in the cortical spinal tracts, corona radiate, corpus callosum, external capsule, thalamic radiations, superior and inferior longitudinal fasciculus, and inferior frontal-occipital fasciculus in the Huntington disease group compared to the control and presymptomatic groups. Reduction of fractional anisotropy is indicative of a degenerative process and axonal loss. There was no statistically significant difference between the presymptomatic and control groups.

Conclusion

White matter integrity is affected in huntingtin gene mutation symptomatic individuals, but other studies with larger samples are required to assess its usefulness in the progression of the neurodegenerative process.

RESUMO

Objetivo

Avaliar o envolvimento da substância branca (SB) cerebral em indivíduos com mutação do gene da huntingtina.

Métodos

Foram avaliados 34 indivíduos: 11 com mutação do gene da huntingtina sintomática, 12 assintomáticos com mutação do gene da huntingtina e 11 indivíduos controles. Realizamos ressonância magnética cerebral para avaliar a integridade da SB usando o tensor de difusão (DTI), com medição da anisotrofia fracionada (FA).

Resultados

Observamos uma diminuição da FA no trato corticoespinhal, coroa radiada, corpo caloso (joelho, corpo e esplênio), cápsula externa, radiações talâmicas, fascículo longitudinal superior e inferior, e fascículo frontal-occipital inferior no grupo dos indivíduos com mutação sintomática. A redução da FA é indicativa de processo degenerativo e perda axonal. Não houve diferença estatística entre os grupos controle e pré-sintomático.

Conclusão

Houve comprometimento da integridade da SB em indivíduos com mutação no gene da Huntingtina sintomática, mas outros estudos são necessários para avaliar a sua utilidade na progressão do processo neurodegenerativo.

Huntington disease - biomarkers - neuroimaging

doença de Huntington - biomarcadores - neuroimagem

• References

• 1 Weir DW, Sturrock A, Leavitt BR. Development of biomarkers for Huntington’s disease. Lancet Neurol 2011;10(6):573-90. https://doi.org/10.1016/S1474-4422(11)70070-9
• 2 Paulsen JS, Langbehn DR, Stout JC, Aylward E, Ross CA, Nance M et al. Detection of Huntington’s disease decades before diagnosis: the Predict-HD study. J Neurol Neurosurg Psychiatry 2008;79(8):874-80. https://doi.org/10.1136/jnnp.2007.128728
• 3 Aylward EH, Sparks BF, Field KM, Yallapragada V, Shpritz BD, Rosenblatt A et al. Onset and rate of striatal atrophy in preclinical Huntington disease. Neurology 2004;63(1):66-72. https://doi.org/10.1212/01.WNL.0000132965.14653.D1
• 4 Ferrante RJ, Gutekunst CA, Persichetti F, McNeil SM, Kowall NW, Gusella JF et al. Heterogeneous topographic and cellular distribution of huntingtin expression in the normal human neostriatum. J Neurosci 1997;17(9):3052-63.
• 5 Ciarmiello A, Cannella M, Lastoria S, Simonelli M, Frati L, Rubinsztein DC et al. Brain white-matter volume loss and glucose hypometabolism precede the clinical symptoms of Huntington’s disease. J Nucl Med 2006;47(2):215-22.
• 6 Rosas HD, Tuch DS, Hevelone ND, Zaleta AK, Vangel M, Hersch SM et al. Diffusion tensor imaging in presymptomatic and early Huntington’s disease: selective white matter pathology and its relationship to clinical measures. Mov Disord. 2006; 21(9):1317-25. https://doi.org/10.1002/mds.20979
• 7 Basser PJ, Pierpaoli C. Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson. 1996;111(3):209-19. https://doi.org/10.1006/jmrb.1996.0086
• 8 Basser P, Pierpaoli C. Recollections about our 1996 JMR paper on diffusion anisotropy. J Magn Reson. 2011;213(2):571-2. https://doi.org/10.1016/j.jmr.2011.08.023
• 9 Klöppel S, Draganski B, Golding CV, Chu C, Nagy Z, Cook PA et al. White matter connections reflect changes in voluntary-guided saccades in pre-symptomatic Huntington’s disease. Brain. 2008;131(1):196-204. https://doi.org/10.1093/brain/awm275
• 10 Paulsen JS, Nopoulos PC, Aylward E, Ross CA, Johnson H, Magnotta VA et al. Striatal and white matter predictors of estimated diagnosis for Huntington disease. Brain Res Bull. 2010;82(3-4):201-7. https://doi.org/10.1016/j.brainresbull.2010.04.003
• 11 Dumas EM, Bogaard SJ, Ruber ME, Reilman RR, Stout JC, Craufurd D et al. Early changes in white matter pathways of the sensorimotor cortex in premanifest Huntington’s disease. Hum Brain Mapp. 2012;33(1):203-12. https://doi.org/10.1002/hbm.21205
• 12 Huntington Study Group. Unified Huntington’s Disease Rating Scale: reliability and consistency. Mov Disord. 1996;11(2):136-42. https://doi.org/10.1002/mds.870110204
• 13 Tumas V, Camargos ST, Jalali PS, Galesso AP, Marques Junior W. Internal consistency of a Brazilian version of the unified Huntington’s disease rating scale. Arq Neuropsiquiatr. 2004;62(4):977-82. https://doi.org/10.1590/S0004-282X2004000600009
• 14 Brucki SM, Nitrini R, Caramelli P, Bertolucci PH, Okamoto IH. [Suggestions for utilization of the mini-mental state examination in Brazil]. Arq Neuropsiquiatr. 2003;61(3B):777-81. Portuguese. https://doi.org/10.1590/S0004-282X2003000500014
• 15 Duro D, Simões MR, Ponciano E, Santana I. Validation studies of the Portuguese experimental version of the Montreal Cognitive Assessment (MoCA): confirmatory factor analysis. J Neurol. 2010;257(5):728-34. https://doi.org/10.1007/s00415-009-5399-5
• 16 Gorenstein C, Andrade L, Vieira Filho AH, Tung TC, Artes R. Psychometric properties of the Portuguese version of the Beck Depression Inventory on Brazilian college students. J Clin Psychol. 1999;55(5):553-62. https://doi.org/10.1002/(SICI)1097-4679(199905)55:5<553::AID-JCLP3>3.0.CO;2-D
• 17 Tabrizi SJ, Langbehn DR, Leavitt BR, Roos RA, Durr A, Craufurd D et al. Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol. 2009;899):791-801. https://doi.org/10.1016/S1474-4422(09)70170-X
• 18 Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23 Suppl 1:S208-19. https://doi.org/10.1016/j.neuroimage.2004.07.051
• 19 Rueckert D, Sonoda LI, Hayes C, Hill DL, Leach MO, Hawkes DJ. Nonrigid registration using free-form deformations: application to breast MR images. IEEE Trans Med Imaging. 1999;18(8):712-21. https://doi.org/10.1109/42.796284
• 20 Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE et al. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage. 2006;31(4):1487-505. https://doi.org/10.1016/j.neuroimage.2006.02.024
• 21 Bohanna I, Georgiou-Karistianis N, Hannan AJ, Egan GF. Magnetic resonance imaging as an approach towards identifying neuropathological biomarkers for Huntington’s disease. Brain Res Rev. 2008;58(1):209-25. https://doi.org/10.1016/j.brainresrev.2008.04.001
• 22 Mascalchi M, Lolli F, Della Nave R, Tessa C, Petralli R, Gavazzi C et al. Huntington disease: volumetric, diffusion-weighted, and magnetization transfer MR imaging of brain. Radiology. 2004;232(3):867-73. https://doi.org/10.1148/radiol.2322030820
• 23 Stoffers D, Sheldon S, Kuperman JM, Goldstein J, Corey-Bloom J, Aron AR. Contrasting gray and white matter changes in preclinical Huntington disease: an MRI study. Neurology. 2010;74(15):1208-16. https://doi.org/10.1212/WNL.0b013e3181d8c20a
• 24 Novak MJ, Seunarine KK, Gibbard CR, Hobbs NZ, Scahill RI, Clark CA et al. White matter integrity in premanifest and early Huntington’s disease is related to caudate loss and disease progression. Cortex. 2014;52:98-112. https://doi.org/10.1016/j.cortex.2013.11.009
• 25 Rosas HD, Salat DH, Lee SY, Zaleta AK, Pappu V, Fischl B et al. Cerebral cortex and the clinical expression of Huntington’s disease: complexity and heterogeneity. Brain. 2008;131(4):1057-68. https://doi.org/10.1093/brain/awn025
• 26 Weaver KE, Richards TL, Liang O, Laurino MY, Samii A, Aylward EH. Longitudinal diffusion tensor imaging in Huntington’s disease. Exp Neurol. 2009;216(2):525-9. https://doi.org/10.1016/j.expneurol.2008.12.026
• 27 Poudel GR, Stout JC, Dominguez JF, Churchyard A, Chua P, Egan GF et al. Longitudinal change in white matter microstructure in Huntington’s disease: the IMAGE-HD study. Neurobiol Dis. 2015;74:406-12. https://doi.org/10.1016/j.nbd.2014.12.009