Skip to main content
Top
Published in: BMC Neurology 1/2022

Open Access 01-12-2022 | Magnetic Resonance Imaging | Research article

Brainstem lesions are associated with diffuse spinal cord involvement in early multiple sclerosis

Authors: Michaela Andelova, Karolina Vodehnalova, Jan Krasensky, Eliska Hardubejova, Tereza Hrnciarova, Barbora Srpova, Tomas Uher, Ingrid Menkyova, Dominika Stastna, Lucie Friedova, Jiri Motyl, Jana Lizrova Preiningerova, Eva Kubala Havrdova, Bénédicte Maréchal, Mário João Fartaria, Tobias Kober, Dana Horakova, Manuela Vaneckova

Published in: BMC Neurology | Issue 1/2022

Login to get access

Abstract

Background

Early infratentorial and focal spinal cord lesions on magnetic resonance imaging (MRI) are associated with a higher risk of long-term disability in patients with multiple sclerosis (MS). The role of diffuse spinal cord lesions remains less understood. The purpose of this study was to evaluate focal and especially diffuse spinal cord lesions in patients with early relapsing-remitting MS and their association with intracranial lesion topography, global and regional brain volume, and spinal cord volume.

Methods

We investigated 58 MS patients with short disease duration (< 5 years) from a large academic MS center and 58 healthy controls matched for age and sex. Brain, spinal cord, and intracranial lesion volumes were compared among patients with- and without diffuse spinal cord lesions and controls. Binary logistic regression models were used to analyse the association between the volume and topology of intracranial lesions and the presence of focal and diffuse spinal cord lesions.

Results

We found spinal cord involvement in 75% of the patients (43/58), including diffuse changes in 41.4% (24/58). Patients with diffuse spinal cord changes exhibited higher volumes of brainstem lesion volume (p = 0.008). The presence of at least one brainstem lesion was associated with a higher probability of the presence of diffuse spinal cord lesions (odds ratio 47.1; 95% confidence interval 6.9–321.6 p < 0.001) as opposed to focal spinal cord lesions (odds ratio 0.22; p = 0.320). Patients with diffuse spinal cord lesions had a lower thalamus volume compared to patients without diffuse spinal cord lesions (p = 0.007) or healthy controls (p = 0.002).

Conclusions

Diffuse spinal cord lesions are associated with the presence of brainstem lesions and with a lower volume of the thalamus. This association was not found in patients with focal spinal cord lesions. If confirmed, thalamic atrophy in patients with diffuse lesions could increase our knowledge on the worse prognosis in patients with infratentorial and SC lesions.
Appendix
Available only for authorised users
Literature
1.
go back to reference Barkhof F, Scheltens P, Comi GP. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 1997 Nov;120 ( Pt 11):2059–69. Barkhof F, Scheltens P, Comi GP. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 1997 Nov;120 ( Pt 11):2059–69. 
2.
go back to reference Minneboo A, Barkhof F, Polman CH, Uitdehaag BMJ, Knol DL, Castelijns JA. Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis. Arch Neurol. 2004;61:217–21.CrossRef Minneboo A, Barkhof F, Polman CH, Uitdehaag BMJ, Knol DL, Castelijns JA. Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis. Arch Neurol. 2004;61:217–21.CrossRef
3.
go back to reference Tintore M, Rovira A, Arrambide G, Mitjana R, Río J, Auger C, et al. Brainstem lesions in clinically isolated syndromes. Neurology . 2010 ;75(21):1933–8. Tintore M, Rovira A, Arrambide G, Mitjana R, Río J, Auger C, et al. Brainstem lesions in clinically isolated syndromes. Neurology . 2010 ;75(21):1933–8.
4.
go back to reference Silveira F, Sánchez F, Miguez J, Contartese L, Gómez A, Patrucco L, et al. New MRI lesions and topography at 6 months of treatment initiation and disease activity during follow up in relapsing remitting multiple sclerosis patients. Neurol Res. 2020;42:148–52.CrossRef Silveira F, Sánchez F, Miguez J, Contartese L, Gómez A, Patrucco L, et al. New MRI lesions and topography at 6 months of treatment initiation and disease activity during follow up in relapsing remitting multiple sclerosis patients. Neurol Res. 2020;42:148–52.CrossRef
6.
go back to reference Arrambide G, Rovira A, Sastre-Garriga J, Tur C, Castilló J, Río J, et al. Spinal cord lesions: a modest contributor to diagnosis in clinically isolated syndromes but a relevant prognostic factor. Mult Scler J. 2018;24:301–12.CrossRef Arrambide G, Rovira A, Sastre-Garriga J, Tur C, Castilló J, Río J, et al. Spinal cord lesions: a modest contributor to diagnosis in clinically isolated syndromes but a relevant prognostic factor. Mult Scler J. 2018;24:301–12.CrossRef
7.
go back to reference Kohler M, Kohler E, Vrech C, Pappolla A, Miguez J, Patrucco L, et al. Aggressive multiple sclerosis in Argentina: data from the nationwide registry RelevarEM. J Clin Neurosci. 2021;89:360–4.CrossRef Kohler M, Kohler E, Vrech C, Pappolla A, Miguez J, Patrucco L, et al. Aggressive multiple sclerosis in Argentina: data from the nationwide registry RelevarEM. J Clin Neurosci. 2021;89:360–4.CrossRef
8.
go back to reference Weier K, Mazraeh J, Naegelin Y, Thoeni A, Hirsch JG, Fabbro T, et al. Biplanar MRI for the assessment of the spinal cord in multiple sclerosis. Mult Scler J. 2012;18:1560–9.CrossRef Weier K, Mazraeh J, Naegelin Y, Thoeni A, Hirsch JG, Fabbro T, et al. Biplanar MRI for the assessment of the spinal cord in multiple sclerosis. Mult Scler J. 2012;18:1560–9.CrossRef
9.
go back to reference Weier K, Penner IK, Magon S, Amann M, Naegelin Y, Andelova M, et al. Cerebellar abnormalities contribute to disability including cognitive impairment in multiple sclerosis. PLoS One. 2014;9(1):e86916.CrossRef Weier K, Penner IK, Magon S, Amann M, Naegelin Y, Andelova M, et al. Cerebellar abnormalities contribute to disability including cognitive impairment in multiple sclerosis. PLoS One. 2014;9(1):e86916.CrossRef
10.
go back to reference Lycklama G, Thompson A, Filippi M, Miller D, Polman C, Fazekas F, et al. Spinal-cord MRI in multiple sclerosis. Lancet Neurol. 2003;2:555–62.CrossRef Lycklama G, Thompson A, Filippi M, Miller D, Polman C, Fazekas F, et al. Spinal-cord MRI in multiple sclerosis. Lancet Neurol. 2003;2:555–62.CrossRef
11.
go back to reference Hua LH, Donlon SL, Sobhanian MJ, Portner SM, Okuda DT. Thoracic spinal cord lesions are influenced by the degree of cervical spine involvement in multiple sclerosis. Spinal Cord. 2015;53:520–5.CrossRef Hua LH, Donlon SL, Sobhanian MJ, Portner SM, Okuda DT. Thoracic spinal cord lesions are influenced by the degree of cervical spine involvement in multiple sclerosis. Spinal Cord. 2015;53:520–5.CrossRef
12.
go back to reference Bonek R, Orlicka KMZ. Demyelinating lesions in the cervical cord in multiple sclerosis 10 years after onset of the disease. Correlation between MRI parameters and clinical course. Neurol Neurochir Pol. 2007;41(3):229–33.PubMed Bonek R, Orlicka KMZ. Demyelinating lesions in the cervical cord in multiple sclerosis 10 years after onset of the disease. Correlation between MRI parameters and clinical course. Neurol Neurochir Pol. 2007;41(3):229–33.PubMed
14.
go back to reference Lukas C, Sombekke MH, Bellenberg B, Hahn HK, Popescu V, Bendfeldt K, et al. Relevance of spinal cord abnormalities to clinical Disability in Multiple sclerosis: MR Imaging Findings in a Large Cohort of Patients. Radiol n Radiol. 2013;269:542–52. Lukas C, Sombekke MH, Bellenberg B, Hahn HK, Popescu V, Bendfeldt K, et al. Relevance of spinal cord abnormalities to clinical Disability in Multiple sclerosis: MR Imaging Findings in a Large Cohort of Patients. Radiol n Radiol. 2013;269:542–52.
15.
go back to reference Andelova M, Uher T, Krasensky J, Sobisek L, Kusova E, Srpova B, et al. Additive effect of spinal cord volume, diffuse and focal cord pathology on disability in multiple sclerosis. Front Neurol. 2019;10:820.CrossRef Andelova M, Uher T, Krasensky J, Sobisek L, Kusova E, Srpova B, et al. Additive effect of spinal cord volume, diffuse and focal cord pathology on disability in multiple sclerosis. Front Neurol. 2019;10:820.CrossRef
16.
go back to reference Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17:162–73.CrossRef Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17:162–73.CrossRef
17.
go back to reference Gass A, Rocca MA, Agosta F, Ciccarelli O, Chard D, Valsasina P, et al. MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis. Lancet Neurol. 2015;14(4):443–54.CrossRef Gass A, Rocca MA, Agosta F, Ciccarelli O, Chard D, Valsasina P, et al. MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis. Lancet Neurol. 2015;14(4):443–54.CrossRef
18.
go back to reference Tsagkas C, Naegelin Y, Amann M, Papadopoulou A, Barro C, Chakravarty MM, et al. Central nervous system atrophy predicts future dynamics of disability progression in a real-world multiple sclerosis cohort. Eur J Neurol. 2021;28(12):4153–66.CrossRef Tsagkas C, Naegelin Y, Amann M, Papadopoulou A, Barro C, Chakravarty MM, et al. Central nervous system atrophy predicts future dynamics of disability progression in a real-world multiple sclerosis cohort. Eur J Neurol. 2021;28(12):4153–66.CrossRef
19.
go back to reference Bischof A, Papinutto N, Keshavan A, Rajesh A, Kirkish G, Zhang X, et al. Spinal cord atrophy predicts progressive disease in relapsing multiple sclerosis. Ann Neurol. 2022;91:268–81.CrossRef Bischof A, Papinutto N, Keshavan A, Rajesh A, Kirkish G, Zhang X, et al. Spinal cord atrophy predicts progressive disease in relapsing multiple sclerosis. Ann Neurol. 2022;91:268–81.CrossRef
21.
go back to reference Nijeholt GJ LÀ, Barkhof F, Scheltens P, Castelijns JA, Adèr H, Van Waesberghe JH, et al. MR of the spinal cord in multiple sclerosis: relation to clinical subtype and disability. Am J Neuroradiol. 1997;18(6):1041–8. Nijeholt GJ LÀ, Barkhof F, Scheltens P, Castelijns JA, Adèr H, Van Waesberghe JH, et al. MR of the spinal cord in multiple sclerosis: relation to clinical subtype and disability. Am J Neuroradiol. 1997;18(6):1041–8.
24.
go back to reference Fartaria MJ, Kober T, Granziera C, Bach CM. Longitudinal analysis of white matter and cortical lesions in multiple sclerosis. NeuroImage Clin. 2019;23:101938.CrossRef Fartaria MJ, Kober T, Granziera C, Bach CM. Longitudinal analysis of white matter and cortical lesions in multiple sclerosis. NeuroImage Clin. 2019;23:101938.CrossRef
25.
go back to reference Bot JC, Barkhof F, Polman CH, Lycklama à Nijeholt GJ, de Groot V, Bergers E, Ader HJ CJ. Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination. Neurology. 2004;Jan;27 62(2):226–33.CrossRef Bot JC, Barkhof F, Polman CH, Lycklama à Nijeholt GJ, de Groot V, Bergers E, Ader HJ CJ. Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination. Neurology. 2004;Jan;27 62(2):226–33.CrossRef
26.
go back to reference Eriksson M, Andersen O, Runmarker B. Long-term follow up of patients with clinically isolated syndromes, relapsing-remitting and secondary progressive multiple sclerosis. Mult Scler. 2003;9:260–74.CrossRef Eriksson M, Andersen O, Runmarker B. Long-term follow up of patients with clinically isolated syndromes, relapsing-remitting and secondary progressive multiple sclerosis. Mult Scler. 2003;9:260–74.CrossRef
27.
go back to reference Qiu W, Raven S, James I, Luo Y, Wu J, Castley A, et al. Spinal cord involvement in multiple sclerosis: a correlative MRI and high-resolution HLA-DRB1 genotyping study. J Neurol Sci. 2011;300:114–9.CrossRef Qiu W, Raven S, James I, Luo Y, Wu J, Castley A, et al. Spinal cord involvement in multiple sclerosis: a correlative MRI and high-resolution HLA-DRB1 genotyping study. J Neurol Sci. 2011;300:114–9.CrossRef
28.
go back to reference Droby A, Fleischer V, Carnini M, Zimmermann H, Siffrin V, Gawehn J, et al. The impact of isolated lesions on white-matter fiber tracts in multiple sclerosis patients. NeuroImage Clin. 2015;8:110–6.CrossRef Droby A, Fleischer V, Carnini M, Zimmermann H, Siffrin V, Gawehn J, et al. The impact of isolated lesions on white-matter fiber tracts in multiple sclerosis patients. NeuroImage Clin. 2015;8:110–6.CrossRef
29.
go back to reference Nijeholt GJ L à, Bergers E, Kamphorst W, Bot J, Nicolay K, Castelijns JA, et al. Post-mortem high-resolution MRI of the spinal cord in multiple sclerosis a correlative study with conventional MRI, histopathology and clinical phenotype. Brain. 2001;124:154–66.CrossRef Nijeholt GJ L à, Bergers E, Kamphorst W, Bot J, Nicolay K, Castelijns JA, et al. Post-mortem high-resolution MRI of the spinal cord in multiple sclerosis a correlative study with conventional MRI, histopathology and clinical phenotype. Brain. 2001;124:154–66.CrossRef
30.
go back to reference Bot JCJ, Blezer ELA, Kamphorst W, Nijeholt GJ LÀ, Ader HJ, Castelijns JA, et al. The spinal cord in multiple sclerosis: relationship of high-spatial- resolution quantitative MR imaging findings to histopathologic results. Radiology. 2004;233:531–40.CrossRef Bot JCJ, Blezer ELA, Kamphorst W, Nijeholt GJ LÀ, Ader HJ, Castelijns JA, et al. The spinal cord in multiple sclerosis: relationship of high-spatial- resolution quantitative MR imaging findings to histopathologic results. Radiology. 2004;233:531–40.CrossRef
31.
go back to reference Bergers E, Bot JCJ, De Groot CJA, Polman CH, Nijeholt GJ L à, Castelijns JA, et al. Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions. Neurology. 2002;59:1766–71.CrossRef Bergers E, Bot JCJ, De Groot CJA, Polman CH, Nijeholt GJ L à, Castelijns JA, et al. Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions. Neurology. 2002;59:1766–71.CrossRef
32.
go back to reference Sombekke MH, Lukas C, Bart ; J, Crusius A, Tejedor D, Killestein J, et al. HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis. Arch Neurol. 2009;66(12):1531–6. Sombekke MH, Lukas C, Bart ; J, Crusius A, Tejedor D, Killestein J, et al. HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis. Arch Neurol. 2009;66(12):1531–6.
33.
go back to reference Ganesvaran G, Greer JM, Pender MP. Prominent brainstem and cerebellar involvement in multiple sclerosis with psoriasis. Mult Scler. 2009;15:763–6.CrossRef Ganesvaran G, Greer JM, Pender MP. Prominent brainstem and cerebellar involvement in multiple sclerosis with psoriasis. Mult Scler. 2009;15:763–6.CrossRef
34.
go back to reference Greer JM, Csurhes PA, Muller DM, Pender MP. Correlation of blood T cell and antibody reactivity to myelin proteins with HLA type and lesion localization in multiple sclerosis. J Immunol. 2008;180(9):6402–10. Greer JM, Csurhes PA, Muller DM, Pender MP. Correlation of blood T cell and antibody reactivity to myelin proteins with HLA type and lesion localization in multiple sclerosis. J Immunol. 2008;180(9):6402–10.
35.
go back to reference Biberacher V, Boucard CC, Schmidt P, Engl C, Buck D, Berthele A, et al. Atrophy and structural variability of the upper cervical cord in early multiple sclerosis. Mult Scler. 2015;21:875–84.CrossRef Biberacher V, Boucard CC, Schmidt P, Engl C, Buck D, Berthele A, et al. Atrophy and structural variability of the upper cervical cord in early multiple sclerosis. Mult Scler. 2015;21:875–84.CrossRef
37.
go back to reference Azevedo CJ, Overton E, Khadka S, Buckley J, Liu S, Sampat M, et al. Early CNS neurodegeneration in radiologically isolated syndrome. Neurol Neuroimmunol Neuroinflamm. 2015;2(3):e102. Azevedo CJ, Overton E, Khadka S, Buckley J, Liu S, Sampat M, et al. Early CNS neurodegeneration in radiologically isolated syndrome. Neurol Neuroimmunol Neuroinflamm. 2015;2(3):e102.
38.
go back to reference Henry RG, Shieh M, Okuda DT, Evangelista A, Gorno-Tempini ML, Pelletier D. Regional grey matter atrophy in clinically isolated syndromes at presentation. J Neurol Neurosurg Psychiatry. 2008;79:1236–44.CrossRef Henry RG, Shieh M, Okuda DT, Evangelista A, Gorno-Tempini ML, Pelletier D. Regional grey matter atrophy in clinically isolated syndromes at presentation. J Neurol Neurosurg Psychiatry. 2008;79:1236–44.CrossRef
39.
go back to reference Dekker I, Schoonheim MM, Venkatraghavan V, Eijlers AJC, Brouwer I, Bron EE, et al. The sequence of structural, functional and cognitive changes in multiple sclerosis. NeuroImage Clin. 2021;29:102550.CrossRef Dekker I, Schoonheim MM, Venkatraghavan V, Eijlers AJC, Brouwer I, Bron EE, et al. The sequence of structural, functional and cognitive changes in multiple sclerosis. NeuroImage Clin. 2021;29:102550.CrossRef
40.
go back to reference Wagenknecht N, Becker B, Scheld M, Beyer C, Clarner T, Hochstrasser T, et al. Thalamus degeneration and inflammation in two distinct multiple sclerosis animal models. J Mol Neurosci. 2016;60(1):102–14.CrossRef Wagenknecht N, Becker B, Scheld M, Beyer C, Clarner T, Hochstrasser T, et al. Thalamus degeneration and inflammation in two distinct multiple sclerosis animal models. J Mol Neurosci. 2016;60(1):102–14.CrossRef
42.
go back to reference Eshaghi A, Prados F, Brownlee WJ, Altmann DR, Tur C, Cardoso MJ, et al. Deep gray matter volume loss drives disability worsening in multiple sclerosis. Ann Neurol. 2018;83(2):210–22.CrossRef Eshaghi A, Prados F, Brownlee WJ, Altmann DR, Tur C, Cardoso MJ, et al. Deep gray matter volume loss drives disability worsening in multiple sclerosis. Ann Neurol. 2018;83(2):210–22.CrossRef
43.
go back to reference Magon S, Tsagkas C, Gaetano L, Patel R, Naegelin Y, Amann M, et al. Volume loss in the deep gray matter and thalamic subnuclei: a longitudinal study on disability progression in multiple sclerosis. J Neurol. 2020;267(5):1536–46.CrossRef Magon S, Tsagkas C, Gaetano L, Patel R, Naegelin Y, Amann M, et al. Volume loss in the deep gray matter and thalamic subnuclei: a longitudinal study on disability progression in multiple sclerosis. J Neurol. 2020;267(5):1536–46.CrossRef
44.
go back to reference Combès B, Kerbrat A, Ferré JC, Callot V, Maranzano J, Badji A, et al. Focal and diffuse cervical spinal cord damage in patients with early relapsing–remitting MS: a multicentre magnetisation transfer ratio study. Mult Scler. 2019;25(8):1113–23. Combès B, Kerbrat A, Ferré JC, Callot V, Maranzano J, Badji A, et al. Focal and diffuse cervical spinal cord damage in patients with early relapsing–remitting MS: a multicentre magnetisation transfer ratio study. Mult Scler. 2019;25(8):1113–23.
45.
go back to reference Oh J, Saidha S, Chen M, Smith SA, Prince J, Jones C, et al. Spinal cord quantitative MRI discriminates between disability levels in multiple sclerosis. Neurology. 2013;80(6):540-7. Oh J, Saidha S, Chen M, Smith SA, Prince J, Jones C, et al. Spinal cord quantitative MRI discriminates between disability levels in multiple sclerosis. Neurology. 2013;80(6):540-7.
46.
go back to reference Von Meyenburg J, Wilm BJ, Weck A, Petersen J, Gallus E, Mathys J, et al. Spinal cord diffusion-tensor imaging and motor-evoked potentials in multiple sclerosis patients: microstructural and functional asymmetry. Radiology. 2013;267:869–79.CrossRef Von Meyenburg J, Wilm BJ, Weck A, Petersen J, Gallus E, Mathys J, et al. Spinal cord diffusion-tensor imaging and motor-evoked potentials in multiple sclerosis patients: microstructural and functional asymmetry. Radiology. 2013;267:869–79.CrossRef
47.
go back to reference Eden D. Spatial distribution of multiple sclerosis lesions in the cervical spinal cord. Brain. 2019;142(3):633–46.CrossRef Eden D. Spatial distribution of multiple sclerosis lesions in the cervical spinal cord. Brain. 2019;142(3):633–46.CrossRef
Metadata
Title
Brainstem lesions are associated with diffuse spinal cord involvement in early multiple sclerosis
Authors
Michaela Andelova
Karolina Vodehnalova
Jan Krasensky
Eliska Hardubejova
Tereza Hrnciarova
Barbora Srpova
Tomas Uher
Ingrid Menkyova
Dominika Stastna
Lucie Friedova
Jiri Motyl
Jana Lizrova Preiningerova
Eva Kubala Havrdova
Bénédicte Maréchal
Mário João Fartaria
Tobias Kober
Dana Horakova
Manuela Vaneckova
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2022
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-022-02778-z

Other articles of this Issue 1/2022

BMC Neurology 1/2022 Go to the issue