In vivo molecular signatures of cervical spinal cord pathology in degenerative compression

Tomas Horak; Magda Horakova; Alena Svatkova; Zdenek Kadanka; Petr Kudlicka; Jan Valosek; Tomas Rohan; Milos Kerkovsky; Eva Vlckova; Zdenek Kadanka; Dinesh K. Deelchand; Pierre Gilles Henry; Josef Bednarik; Petr Bednarik

doi:10.1089/neu.2021.0151

In vivo molecular signatures of cervical spinal cord pathology in degenerative compression

Tomas Horak, Magda Horakova, Alena Svatkova, Zdenek Kadanka, Petr Kudlicka, Jan Valosek, Tomas Rohan, Milos Kerkovsky, Eva Vlckova, Zdenek Kadanka, Dinesh K. Deelchand, Pierre Gilles Henry, Josef Bednarik, Petr Bednarik

Center for Magnetic Resonance Research

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Degenerative cervical myelopathy (DCM) is a severe consequence of degenerative cervical spinal cord (CSC) compression. The non-myelopathic stage of compression (NMDC) is highly prevalent and often progresses to disabling DCM. This study aims to disclose markers of progressive neurochemical alterations in NMDC and DCM by utilizing an approach based on state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Proton-MRS data were prospectively acquired from 73 participants with CSC compression and 47 healthy controls (HCs). The MRS voxel was centered at the C2 level. Compression-affected participants were clinically categorized as NMDC and DCM, radiologically as mild (MC) or severe (SC) compression. CSC volumes and neurochemical concentrations were compared between cohorts (HC vs. NMDC vs. DCM and HC vs. MC vs. SC) with general linear models adjusted for age and height (pFWE < 0.05) and correlated to stenosis severity, electrophysiology, and myelopathy symptoms (p < 0.05). Whereas the ratio of total creatine (tCr) to total N-acetylaspartate (tNAA) increased in NMDC (+11%) and in DCM (+26%) and SC (+21%), myo-inositol/tNAA, glutamate + glutamine/tNAA, and volumes changed only in DCM (+20%, +73%, and -14%) and SC (+12%, +46%, and -8%, respectively) relative to HCs. Both tCr/tNAA and myo-inositol/tNAA correlated with compression severity and volume (-0.376 < r < -0.259). Myo-inositol/tNAA correlated with myelopathy symptoms (r = -0.670), whereas CSC volume did not. Short-echo 1H-MRS provided neurochemical signatures of CSC impairment that reflected compression severity and clinical significance. Whereas volumetry only reflected clinically manifest myelopathy (DCM), MRS detected neurochemical changes already before the onset of myelopathy symptoms.

Original language	English (US)
Pages (from-to)	2999-3010
Number of pages	12
Journal	Journal of neurotrauma
Volume	38
Issue number	21
DOIs	https://doi.org/10.1089/neu.2021.0151
State	Published - Nov 1 2021

Bibliographical note

Funding Information:
The Center for Magnetic Resonance Research, University of Minnesota is supported, in part, by NIH Center grants P41EB027061 and P30NS076408.

Funding Information:
We acknowledge the core facility of the Multimodal and Functional Imaging Laboratory, Masaryk University, CEITEC supported by MEYS CR (LM2018129 Czech-BioImaging). Access to computing and storage facilities owned by parties and projects contributing to the National Grid Infrastructure MetaCentrum provided under the program ‘‘Projects of Large Research, Development, and Innovations Infrastructures’’ (CESNET LM2015042), is greatly appreciated.

Funding Information:
This research was funded by Czech Health Research Council grants ref. NV18-04-00159 and by the Ministry of Health of the Czech Republic project for conceptual development in research organizations, ref. 65269705 (University Hospital, Brno, Czech Republic).

Funding Information:
A.S. has received funding from the European Union’s Horizon 2020 research and innovation program under a Marie Sk1odowska-Curie grant agreement (no. 794986). P.B. was partially supported by the European Union’s Horizon 2020 research and innovation program under a Marie Sk1odowska-Curie grant agreement (no. 846793) and by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (no. 27238).

Publisher Copyright:
© Tomas Horak et al., 2021; Published by Mary Ann Liebert, Inc. 2021.

Keywords

cervical spinal cord, compression, degenerative
magnetic resonance
myelopathy
spectroscopy

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Horak, T., Horakova, M., Svatkova, A., Kadanka, Z., Kudlicka, P., Valosek, J., Rohan, T., Kerkovsky, M., Vlckova, E., Kadanka, Z., Deelchand, D. K., Henry, P. G., Bednarik, J., & Bednarik, P. (2021). In vivo molecular signatures of cervical spinal cord pathology in degenerative compression. Journal of neurotrauma, 38(21), 2999-3010. https://doi.org/10.1089/neu.2021.0151

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abstract = "Degenerative cervical myelopathy (DCM) is a severe consequence of degenerative cervical spinal cord (CSC) compression. The non-myelopathic stage of compression (NMDC) is highly prevalent and often progresses to disabling DCM. This study aims to disclose markers of progressive neurochemical alterations in NMDC and DCM by utilizing an approach based on state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Proton-MRS data were prospectively acquired from 73 participants with CSC compression and 47 healthy controls (HCs). The MRS voxel was centered at the C2 level. Compression-affected participants were clinically categorized as NMDC and DCM, radiologically as mild (MC) or severe (SC) compression. CSC volumes and neurochemical concentrations were compared between cohorts (HC vs. NMDC vs. DCM and HC vs. MC vs. SC) with general linear models adjusted for age and height (pFWE < 0.05) and correlated to stenosis severity, electrophysiology, and myelopathy symptoms (p < 0.05). Whereas the ratio of total creatine (tCr) to total N-acetylaspartate (tNAA) increased in NMDC (+11%) and in DCM (+26%) and SC (+21%), myo-inositol/tNAA, glutamate + glutamine/tNAA, and volumes changed only in DCM (+20%, +73%, and -14%) and SC (+12%, +46%, and -8%, respectively) relative to HCs. Both tCr/tNAA and myo-inositol/tNAA correlated with compression severity and volume (-0.376 < r < -0.259). Myo-inositol/tNAA correlated with myelopathy symptoms (r = -0.670), whereas CSC volume did not. Short-echo 1H-MRS provided neurochemical signatures of CSC impairment that reflected compression severity and clinical significance. Whereas volumetry only reflected clinically manifest myelopathy (DCM), MRS detected neurochemical changes already before the onset of myelopathy symptoms.",

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author = "Tomas Horak and Magda Horakova and Alena Svatkova and Zdenek Kadanka and Petr Kudlicka and Jan Valosek and Tomas Rohan and Milos Kerkovsky and Eva Vlckova and Zdenek Kadanka and Deelchand, {Dinesh K.} and Henry, {Pierre Gilles} and Josef Bednarik and Petr Bednarik",

note = "Funding Information: The Center for Magnetic Resonance Research, University of Minnesota is supported, in part, by NIH Center grants P41EB027061 and P30NS076408. Funding Information: We acknowledge the core facility of the Multimodal and Functional Imaging Laboratory, Masaryk University, CEITEC supported by MEYS CR (LM2018129 Czech-BioImaging). Access to computing and storage facilities owned by parties and projects contributing to the National Grid Infrastructure MetaCentrum provided under the program {\textquoteleft}{\textquoteleft}Projects of Large Research, Development, and Innovations Infrastructures{\textquoteright}{\textquoteright} (CESNET LM2015042), is greatly appreciated. Funding Information: This research was funded by Czech Health Research Council grants ref. NV18-04-00159 and by the Ministry of Health of the Czech Republic project for conceptual development in research organizations, ref. 65269705 (University Hospital, Brno, Czech Republic). Funding Information: A.S. has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation program under a Marie Sk1odowska-Curie grant agreement (no. 794986). P.B. was partially supported by the European Union{\textquoteright}s Horizon 2020 research and innovation program under a Marie Sk1odowska-Curie grant agreement (no. 846793) and by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (no. 27238). Publisher Copyright: {\textcopyright} Tomas Horak et al., 2021; Published by Mary Ann Liebert, Inc. 2021.",

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doi = "10.1089/neu.2021.0151",

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AU - Kadanka, Zdenek

AU - Kudlicka, Petr

AU - Valosek, Jan

AU - Rohan, Tomas

AU - Kerkovsky, Milos

AU - Vlckova, Eva

AU - Kadanka, Zdenek

AU - Deelchand, Dinesh K.

AU - Henry, Pierre Gilles

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N1 - Funding Information: The Center for Magnetic Resonance Research, University of Minnesota is supported, in part, by NIH Center grants P41EB027061 and P30NS076408. Funding Information: We acknowledge the core facility of the Multimodal and Functional Imaging Laboratory, Masaryk University, CEITEC supported by MEYS CR (LM2018129 Czech-BioImaging). Access to computing and storage facilities owned by parties and projects contributing to the National Grid Infrastructure MetaCentrum provided under the program ‘‘Projects of Large Research, Development, and Innovations Infrastructures’’ (CESNET LM2015042), is greatly appreciated. Funding Information: This research was funded by Czech Health Research Council grants ref. NV18-04-00159 and by the Ministry of Health of the Czech Republic project for conceptual development in research organizations, ref. 65269705 (University Hospital, Brno, Czech Republic). Funding Information: A.S. has received funding from the European Union’s Horizon 2020 research and innovation program under a Marie Sk1odowska-Curie grant agreement (no. 794986). P.B. was partially supported by the European Union’s Horizon 2020 research and innovation program under a Marie Sk1odowska-Curie grant agreement (no. 846793) and by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (no. 27238). Publisher Copyright: © Tomas Horak et al., 2021; Published by Mary Ann Liebert, Inc. 2021.

PY - 2021/11/1

Y1 - 2021/11/1

N2 - Degenerative cervical myelopathy (DCM) is a severe consequence of degenerative cervical spinal cord (CSC) compression. The non-myelopathic stage of compression (NMDC) is highly prevalent and often progresses to disabling DCM. This study aims to disclose markers of progressive neurochemical alterations in NMDC and DCM by utilizing an approach based on state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Proton-MRS data were prospectively acquired from 73 participants with CSC compression and 47 healthy controls (HCs). The MRS voxel was centered at the C2 level. Compression-affected participants were clinically categorized as NMDC and DCM, radiologically as mild (MC) or severe (SC) compression. CSC volumes and neurochemical concentrations were compared between cohorts (HC vs. NMDC vs. DCM and HC vs. MC vs. SC) with general linear models adjusted for age and height (pFWE < 0.05) and correlated to stenosis severity, electrophysiology, and myelopathy symptoms (p < 0.05). Whereas the ratio of total creatine (tCr) to total N-acetylaspartate (tNAA) increased in NMDC (+11%) and in DCM (+26%) and SC (+21%), myo-inositol/tNAA, glutamate + glutamine/tNAA, and volumes changed only in DCM (+20%, +73%, and -14%) and SC (+12%, +46%, and -8%, respectively) relative to HCs. Both tCr/tNAA and myo-inositol/tNAA correlated with compression severity and volume (-0.376 < r < -0.259). Myo-inositol/tNAA correlated with myelopathy symptoms (r = -0.670), whereas CSC volume did not. Short-echo 1H-MRS provided neurochemical signatures of CSC impairment that reflected compression severity and clinical significance. Whereas volumetry only reflected clinically manifest myelopathy (DCM), MRS detected neurochemical changes already before the onset of myelopathy symptoms.

AB - Degenerative cervical myelopathy (DCM) is a severe consequence of degenerative cervical spinal cord (CSC) compression. The non-myelopathic stage of compression (NMDC) is highly prevalent and often progresses to disabling DCM. This study aims to disclose markers of progressive neurochemical alterations in NMDC and DCM by utilizing an approach based on state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Proton-MRS data were prospectively acquired from 73 participants with CSC compression and 47 healthy controls (HCs). The MRS voxel was centered at the C2 level. Compression-affected participants were clinically categorized as NMDC and DCM, radiologically as mild (MC) or severe (SC) compression. CSC volumes and neurochemical concentrations were compared between cohorts (HC vs. NMDC vs. DCM and HC vs. MC vs. SC) with general linear models adjusted for age and height (pFWE < 0.05) and correlated to stenosis severity, electrophysiology, and myelopathy symptoms (p < 0.05). Whereas the ratio of total creatine (tCr) to total N-acetylaspartate (tNAA) increased in NMDC (+11%) and in DCM (+26%) and SC (+21%), myo-inositol/tNAA, glutamate + glutamine/tNAA, and volumes changed only in DCM (+20%, +73%, and -14%) and SC (+12%, +46%, and -8%, respectively) relative to HCs. Both tCr/tNAA and myo-inositol/tNAA correlated with compression severity and volume (-0.376 < r < -0.259). Myo-inositol/tNAA correlated with myelopathy symptoms (r = -0.670), whereas CSC volume did not. Short-echo 1H-MRS provided neurochemical signatures of CSC impairment that reflected compression severity and clinical significance. Whereas volumetry only reflected clinically manifest myelopathy (DCM), MRS detected neurochemical changes already before the onset of myelopathy symptoms.

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In vivo molecular signatures of cervical spinal cord pathology in degenerative compression

Abstract

Bibliographical note

Keywords

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