Wide-spread brain alterations early after the onset of Crohn's disease in children in remission-a pilot study
Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic-ecollection
Document type Journal Article
Grant support
P41 EB027061
NIBIB NIH HHS - United States
PubMed
39691628
PubMed Central
PMC11649648
DOI
10.3389/fnins.2024.1491770
Knihovny.cz E-resources
- Keywords
- Crohn’s disease, MRI relaxometry, brain oedema, diffusion tensor imaging, neuroinflammation,
- Publication type
- Journal Article MeSH
BACKGROUND: The research on possible cerebral involvement in Crohn's disease (CD) has been largely marginalized and failed to capitalize on recent developments in magnetic resonance imaging (MRI). OBJECTIVE: This cross-sectional pilot study searches for eventual macrostructural and microstructural brain affection in CD in remission and early after the disease onset. METHODS: 14 paediatric CD patients and 14 healthy controls underwent structural, diffusion weighted imaging and quantitative relaxation metrics acquisition, both conventional free precession and adiabatic rotating frame transverse and longitudinal relaxation time constants as markers of myelination, iron content and cellular loss. RESULTS: While no inter-group differences in cortical thickness and relaxation metrics were found, lower mean diffusivity and higher intracellular volume fraction were detected in CD patients over vast cortical regions essential for the regulation of the autonomous nervous system, sensorimotor processing, cognition and behavior, pointing to wide-spread cytotoxic oedema in the absence of demyelination, iron deposition or atrophy. CONCLUSION: Although still requiring further validation in longitudinal projects enrolling larger numbers of subjects, this study provides an indication of wide-spread cortical oedema in CD patients very early after the disease onset and sets possible directions for further research.
Center for Magnetic Resonance Research University of Minnesota Minneapolis MN United States
Central European Institute of Technology Masaryk University Neuroscience Centre Brno Czechia
Department of Cybernetics Czech Technical University Prague Prague Czechia
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Bao C., Liu P., Liu H., Jin X., Shi Y., Wu L., et al. . (2018). Difference in regional neural fluctuations and functional connectivity in Crohn’s disease: a resting-state functional MRI study. Brain Imaging Behav. 12, 1795–1803. doi: 10.1007/s11682-018-9850-z, PMID: PubMed DOI PMC
Bao C. H., Liu P., Liu H. R., Wu L. Y., Jin X. M., Wang S. Y., et al. . (2016). Differences in regional homogeneity between patients with Crohn’s disease with and without abdominal pain revealed by resting-state functional magnetic resonance imaging. Pain 157, 1037–1044. doi: 10.1097/j.pain.0000000000000479, PMID: PubMed DOI PMC
Bao C. H., Liu P., Liu H. R., Wu L. Y., Shi Y., Chen W. F., et al. . (2015). Alterations in brain Grey matter structures in patients with Crohn’s disease and their correlation with psychological distress☆. J. Crohn's Colitis 9, 532–540. doi: 10.1093/ecco-jcc/jjv057, PMID: PubMed DOI
Bao C., Liu P., Shi Y., Wu L., Jin X., Zeng X., et al. . (2017). Differences in brain gray matter volume in patients with Crohn’s disease with and without abdominal pain. Oncotarget 8:93624. doi: 10.18632/oncotarget.21161, PMID: PubMed DOI PMC
Benjamin D. J., Berger J. O., Johannesson M., Nosek B. A., Wagenmakers E. J., Berk R., et al. . (2018). Redefine statistical significance. Nat. Hum. Behav. 2, 6–10. doi: 10.1038/s41562-017-0189-z, PMID: PubMed DOI
Benjamini Y., Hochberg Y. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. Royal Stat. Soc. Series B 57, 289–300.
Bonaz B. L., Bernstein C. N. (2013). Brain-gut interactions in inflammatory bowel disease. Gastroenterology 144, 36–49. doi: 10.1053/j.gastro.2012.10.003, PMID: PubMed DOI
Bonaz B., Rivest S. (1998). Effect of a chronic stress on CRF neuronal activity and expression of its type 1 receptor in the rat brain. Am. J. Phys. Regul. Integr. Comp. Phys. 275, R1438–R1449. doi: 10.1152/ajpregu.1998.275.5.R1438, PMID: PubMed DOI
Bora E., Fornito A., Pantelis C., Yücel M. (2012). Gray matter abnormalities in major depressive disorder: a meta-analysis of voxel based morphometry studies. J. Affect. Disord. 138, 9–18. doi: 10.1016/j.jad.2011.03.049, PMID: PubMed DOI
Bronský J., Beránková K., Černá Z., Čopová I., Durilová M., Hradský O., et al. . (2017). Czech working Group for Paediatric Gastroenterology and Nutrition guidelines for diagnostics and treatment of inflammatory bowel diseases in children – 1st edition update. Gastroent Hepatol. 71, 11–18.
Button K. S., Ioannidis J. P. A., Mokrysz C., Nosek B. A., Flint J., Robinson E. S. J., et al. . (2013). Power failure: why small sample size undermines the reliability of neuroscience. Nat. Rev. Neurosci. 14, 365–376. doi: 10.1038/nrn3475, PMID: PubMed DOI
Chrousos G. P. (2009). Stress and disorders of the stress system. Nat. Rev. Endocrinol. 5:374. doi: 10.1038/nrendo.2009.106, PMID: PubMed DOI
Elsehety A., Bertorini T. E. (1997). Neurologic and neuropsychiatric complications of Crohn’s disease. South. Med. J. 90, 606–610. doi: 10.1097/00007611-199706000-00005, PMID: PubMed DOI
Farrokhyar F., Marshall J. K., Easterbrook B., Irvine J. E. (2006). Functional gastrointestinal disorders and mood disorders in patients with inactive inflammatory bowel disease: prevalence and impact on health. Inflamm. Bowel Dis. 12, 38–46. doi: 10.1097/01.MIB.0000195391.49762.89, PMID: PubMed DOI
Filip P., Dufek M., Mangia S., Michaeli S., Bareš M., Schwarz D., et al. . (2021). Alterations in sensorimotor and mesiotemporal cortices and diffuse white matter changes in primary progressive multiple sclerosis detected by adiabatic relaxometry. Front. Neurosci.:1129. PubMed PMC
Filip P., Kokošová V., Valenta Z., Baláž M., Mangia S., Michaeli S., et al. . (2023). Utility of quantitative MRI metrics in brain ageing research. Front. Aging Neurosci.:15. PubMed PMC
Filip P., Svatkova A., Carpenter A. F., Eberly L. E., Nestrasil I., Nissi M. J., et al. . (2020b). Rotating frame MRI relaxations as markers of diffuse white matter abnormalities in multiple sclerosis. NeuroImage 1:102234. PubMed PMC
Filip P., Vojtíšek L., Baláž M., Mangia S., Michaeli S., Šumec R., et al. . (2020a). Differential diagnosis of tremor syndromes using MRI relaxometry. Parkinsonism Relat. Disord. 81, 190–193. doi: 10.1016/j.parkreldis.2020.10.048, PMID: PubMed DOI
Fuhrmann D., Knoll L. J., Blakemore S. J. (2015). Adolescence as a sensitive period of brain development. Trends Cogn. Sci. 19, 558–566. doi: 10.1016/j.tics.2015.07.008, PMID: PubMed DOI
Garwood M., DelaBarre L. (2001). The return of the frequency sweep: designing adiabatic pulses for contemporary NMR. J. Magn. Reson. 153, 155–177. doi: 10.1006/jmre.2001.2340, PMID: PubMed DOI
Glasser M. F., Coalson T. S., Robinson E. C., Hacker C. D., Harwell J., Yacoub E., et al. . (2016). A multi-modal parcellation of human cerebral cortex. Nature 536, 171–178. doi: 10.1038/nature18933, PMID: PubMed DOI PMC
Glasser M. F., Sotiropoulos S. N., Wilson J. A., Coalson T. S., Fischl B., Andersson J. L., et al. . (2013). The minimal preprocessing pipelines for the human connectome project. NeuroImage 80, 105–124. doi: 10.1016/j.neuroimage.2013.04.127, PMID: PubMed DOI PMC
Gobbele R., Reith W., Block F. (2000). Cerebral vasculitis as a concomitant neurological illness in Crohn’s disease. Nervenarzt 71, 299–304. doi: 10.1007/s001150050561, PMID: PubMed DOI
Gray M. A., Chao C. Y., Staudacher H. M., Kolosky N. A., Talley N. J., Holtmann G. (2018). Anti-TNFα therapy in IBD alters brain activity reflecting visceral sensory function and cognitive-affective biases. PLoS One 13:e0193542. doi: 10.1371/journal.pone.0193542, PMID: PubMed DOI PMC
Guerrero J. M., Adluru N., Bendlin B. B., Goldsmith H. H., Schaefer S. M., Davidson R. J., et al. . (2019). Optimizing the intrinsic parallel diffusivity in NODDI: an extensive empirical evaluation. PLoS One 14:e0217118. doi: 10.1371/journal.pone.0217118, PMID: PubMed DOI PMC
Harms M. P., Somerville L. H., Ances B. M., Andersson J., Barch D. M., Bastiani M., et al. . (2018). Extending the human connectome project across ages: imaging protocols for the lifespan development and aging projects. NeuroImage 1, 972–984. PubMed PMC
Hollander D. (2004). Inflammatory bowel diseases and brain-gut axis. J. Physiol. Pharmacol. 55, 183–190. PubMed
Hyams J., Markowitz J., Otley A., Rosh J., Mack D., Bousvaros A., et al. . (2005). Evaluation of the pediatric crohn disease activity index: a prospective multicenter experience. J. Pediatr. Gastroenterol. Nutr. 41, 416–421. doi: 10.1097/01.mpg.0000183350.46795.42, PMID: PubMed DOI
Jabandziev P., Bohosova J., Pinkasova T., Kunovsky L., Slaby O., Goel A. (2020a). The emerging role of noncoding RNAs in pediatric inflammatory bowel disease. Inflamm. Bowel Dis. 26, 985–993. doi: 10.1093/ibd/izaa009, PMID: PubMed DOI PMC
Jabandziev P., Pinkasova T., Kunovsky L., Papez J., Jouza M., Karlinova B., et al. . (2020b). Regional incidence of inflammatory bowel disease in a Czech pediatric population: 16 years of experience (2002–2017). J. Pediatr. Gastroenterol. Nutr. 70:586. doi: 10.1097/MPG.0000000000002660, PMID: PubMed DOI PMC
Ji J. L., Spronk M., Kulkarni K., Repovš G., Anticevic A., Cole M. W. (2019). Mapping the human brain’s cortical-subcortical functional network organization. NeuroImage 15, 35–57. PubMed PMC
Joëls M., Pasricha N., Karst H. (2013). The interplay between rapid and slow corticosteroid actions in brain. Eur. J. Pharmacol. 719, 44–52. doi: 10.1016/j.ejphar.2013.07.015, PMID: PubMed DOI
Kamiya K., Hori M., Aoki S. (2020). NODDI in clinical research. J. Neurosci. Methods 346:108908. doi: 10.1016/j.jneumeth.2020.108908, PMID: PubMed DOI
Kelsen J., Baldassano R. N. (2008). Inflammatory bowel disease: the difference between children and adults. Inflamm. Bowel Dis. 14, S9–S11. doi: 10.1002/ibd.20560 PubMed DOI
Kim E. S., Cho K. B., Park K. S., Jang B. I., Kim K. O., Jeon S. W., et al. . (2013). Predictive factors of impaired quality of life in Korean patients with inactive inflammatory bowel disease: association with functional gastrointestinal disorders and mood disorders. J. Clin. Gastroenterol. 47, e38–e44. doi: 10.1097/MCG.0b013e318266fff5, PMID: PubMed DOI
Lakens D., Adolfi F. G., Albers C. J., Anvari F., Apps M. A., Argamon S. E., et al. . (2018). Justify your alpha. Nat. Hum. Behav. 2, 168–171. doi: 10.1038/s41562-018-0311-x, PMID: PubMed DOI
Levine A., Koletzko S., Turner D., Escher J. C., Cucchiara S., de Ridder L., et al. . (2014). ESPGHAN revised Porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J. Pediatr. Gastroenterol. Nutr. 58, 795–806. doi: 10.1097/MPG.0000000000000239, PMID: PubMed DOI
Levitt M. H., Freeman R., Frenkiel T. (1969). Broadband heteronuclear decoupling. J. Magn. Reson. 47, 328–330.
Loubinoux I., Volk A., Borredon J., Guirimand S., Tiffon B., Seylaz J., et al. . (1997). Spreading of Vasogenic edema and cytotoxic edema assessed by quantitative diffusion and T2 magnetic resonance imaging. Stroke 28, 419–427. doi: 10.1161/01.STR.28.2.419, PMID: PubMed DOI
Mackner L. M., Clough-Paabo E., Pajer K., Lourie A., Crandall W. V. (2011). Psychoneuroimmunologic factors in inflammatory bowel disease. Inflamm. Bowel Dis. 17, 849–857. doi: 10.1002/ibd.21430, PMID: PubMed DOI
Mangia S., Carpenter A. F., Tyan A. E., Eberly L. E., Garwood M., Michaeli S. (2014). Magnetization transfer and adiabatic T1ρ MRI reveal abnormalities in normal-appearing white matter of subjects with multiple sclerosis. Mult. Scler. J. 20, 1066–1073. doi: 10.1177/1352458513515084, PMID: PubMed DOI PMC
Mangia S., Svatkova A., Mascali D., Nissi M. J., Burton P. C., Bednarik P., et al. . (2017). Multi-modal brain MRI in subjects with PD and iRBD. Front. Neurosci. 11:11. doi: 10.3389/fnins.2017.00709 PubMed DOI PMC
Marques J. P., Kober T., Krueger G., van der Zwaag W., Van de Moortele P. F., Gruetter R. (2010). MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1-mapping at high field. NeuroImage 49, 1271–1281. doi: 10.1016/j.neuroimage.2009.10.002, PMID: PubMed DOI
Mawdsley J. E., Rampton D. S. (2005). Psychological stress in IBD: new insights into pathogenic and therapeutic implications. Gut 54, 1481–1491. doi: 10.1136/gut.2005.064261, PMID: PubMed DOI PMC
Michaeli S., Burns T. C., Kudishevich E., Harel N., Hanson T., Sorce D. J., et al. . (2009). Detection of neuronal loss using T1ρ MRI assessment of 1H2O spin dynamics in the aphakia mouse. J. Neurosci. Methods 177, 160–167. doi: 10.1016/j.jneumeth.2008.10.025, PMID: PubMed DOI PMC
Mitsumori F., Watanabe H., Takaya N. (2009). Estimation of brain iron concentration in vivo using a linear relationship between regional iron and apparent transverse relaxation rate of the tissue water at 4.7 T. Magn. Reson. Med. 62, 1326–1330. doi: 10.1002/mrm.22097, PMID: PubMed DOI
Morís G. (2014). Inflammatory bowel disease: an increased risk factor for neurologic complications. World J Gastroenterol: WJG 20:1228. doi: 10.3748/wjg.v20.i5.1228, PMID: PubMed DOI PMC
Nair V. A., Beniwal-Patel P., Mbah I., Young B. M., Prabhakaran V., Saha S. (2016). Structural imaging changes and behavioral correlates in patients with Crohn’s disease in remission. Front. Hum. Neurosci. 10:460. doi: 10.3389/fnhum.2016.00460, PMID: PubMed DOI PMC
Preziosa P., Kiljan S., Steenwijk M. D., Meani A., van de Berg W. D. J., Schenk G. J., et al. . (2019). Axonal degeneration as substrate of fractional anisotropy abnormalities in multiple sclerosis cortex. Brain 142, 1921–1937. doi: 10.1093/brain/awz143, PMID: PubMed DOI
Rankin G. B., Watts H. D., Melnyk C. S., Kelley M. L., Jr. (1979). National Cooperative Crohn’s disease study: extraintestinal manifestations and perianal complications. Gastroenterology 77, 914–920. doi: 10.1016/0016-5085(79)90391-3, PMID: PubMed DOI
Repiso A., Alcántara M., Muñoz-Rosas C., Rodríguez-Merlo R., Pérez-Grueso M. J., Carrobles J. M., et al. . (2006). Extraintestinal manifestations of Crohn’s disease: prevalence and related factors. Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva. 98:510. doi: 10.4321/S1130-01082006000700004 PubMed DOI
Reveley C., Ye F. Q., Mars R. B., Matrov D., Chudasama Y., Leopold D. A. (2022). Diffusion MRI anisotropy in the cerebral cortex is determined by unmyelinated tissue features. Nat. Commun. 13:6702. PubMed PMC
Robinson E. C., Jbabdi S., Glasser M. F., Andersson J., Burgess G. C., Harms M. P., et al. . (2014). MSM: a new flexible framework for multimodal surface matching. NeuroImage 15, 414–426. PubMed PMC
Sevick R. J., Kanda F., Mintorovitch J., Arieff A. I., Kucharczyk J., Tsuruda J. S., et al. . (1992). Cytotoxic brain edema: assessment with diffusion-weighted MR imaging. Radiology 185, 687–690. doi: 10.1148/radiology.185.3.1438745, PMID: PubMed DOI
Smith S. M., Beckmann C. F., Andersson J., Auerbach E. J., Bijsterbosch J., Douaud G., et al. . (2013). Resting-state fMRI in the human connectome project. NeuroImage 80, 144–168. doi: 10.1016/j.neuroimage.2013.05.039, PMID: PubMed DOI PMC
Stovicek J., Liskova P., Lisy J., Hlava S., Keil R. (2014). Crohn’s disease: is there a place for neurological screening? Scand. J. Gastroenterol. 49, 173–176. doi: 10.3109/00365521.2013.867358, PMID: PubMed DOI
Straub R. H., Herfarth H., Falk W., Andus T., Schölmerich J. (2002). Uncoupling of the sympathetic nervous system and the hypothalamic–pituitary–adrenal axis in inflammatory bowel disease? J. Neuroimmunol. 126, 116–125. PubMed
Sutton S. S., Magagnoli J., Cummings T., Hardin J. W. (2019). Association between thiopurine medication exposure and Alzheimer’s disease among a cohort of patients with inflammatory bowel disease. Alzheimers Dement (NY) 5, 809–813. doi: 10.1016/j.trci.2019.10.002 PubMed DOI PMC
Sỳkora J., Pomahačová R., Kreslová M., Cvalínová D., Štych P., Schwarz J. (2018). Current global trends in the incidence of pediatric-onset inflammatory bowel disease. World J. Gastroenterol. 24:2741. doi: 10.3748/wjg.v24.i25.2741, PMID: PubMed DOI PMC
Taché Y., Bonaz B. (2007). Corticotropin-releasing factor receptors and stress-related alterations of gut motor function. J. Clin. Invest. 117, 33–40. doi: 10.1172/JCI30085, PMID: PubMed DOI PMC
Tache Y., Perdue M. H. (2004). Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function. Neurogastroenterol. Motil. 16, 137–142. doi: 10.1111/j.1743-3150.2004.00490.x, PMID: PubMed DOI
Thomann A. K., Thomann P. A., Wolf R. C., Hirjak D., Schmahl C., Ebert M. P., et al. . (2016). Altered markers of brain development in Crohn’s disease with extraintestinal manifestations–a pilot study. PLoS One 11:e0163202. doi: 10.1371/journal.pone.0163202, PMID: PubMed DOI PMC
Tracey K. J. (2002). The inflammatory reflex. Nature 420, 853–859. doi: 10.1038/nature01321, PMID: PubMed DOI
Van Limbergen J., Russell R. K., Drummond H. E., Aldhous M. C., Round N. K., Nimmo E. R., et al. . (2008). Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology 135, 1114–1122. doi: 10.1053/j.gastro.2008.06.081, PMID: PubMed DOI
Weiskopf N., Edwards L. J., Helms G., Mohammadi S., Kirilina E. (2021). Quantitative magnetic resonance imaging of brain anatomy and in vivo histology. Nat. Rev. Phys. 3, 570–588. doi: 10.1038/s42254-021-00326-1, PMID: PubMed DOI
Wills A. J., Tengah D. P., Holmes G. K. (2006). The neurology of enteric disease. J. Neurol. Neurosurg. Psychiatry 77, 805–810. PubMed PMC
Winkler A. M., Ridgway G. R., Webster M. A., Smith S. M., Nichols T. E. (2014). Permutation inference for the general linear model. NeuroImage 15, 381–397. PubMed PMC
Zois C. D., Katsanos K. H., Kosmidou M., Tsianos E. V. (2010). Neurologic manifestations in inflammatory bowel diseases: current knowledge and novel insights. J. Crohn's Colitis 4, 115–124. doi: 10.1016/j.crohns.2009.10.005, PMID: PubMed DOI