Revealing metabolic alterations in spinal cord injury patients with and without neuropathic pain

Poster No:

Th240 

Submission Type:

Abstract Submission 

Authors:

Dario Pfyffer1, Patrik Wyss2, Eveline Huber1, Armin Curt1, Anke Henning2, Patrick Freund1

Institutions:

1Balgrist University Hospital, University of Zurich, Zurich, Switzerland, 2Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

Introduction:

Spinal cord injury (SCI) leads to immediate sensorimotor and autonomic dysfunction below the level of injury and can result in neuropathic pain (NP). Along with neural structural changes [1], neurodegeneration within the sensorimotor system is reflected by biochemical changes in the neural tissue [2]. Magnetic resonance spectroscopy (MRS) non-invasively detects and quantifies several metabolites in vivo which entails molecular information of the tissue. Alterations of cellular processes after SCI have been associated with neurodegeneration in the thalamus [3] and anterior cingulate cortex [4] of SCI patients with NP. However, little is known about how metabolites change after SCI in the cervical cord above the lesion in NP patients. This study therefore aimed to investigate metabolic changes at cervical level in chronic SCI patients with or without NP and assessed the relationships of these biomarkers to clinical measures of NP.

Methods:

We recruited 14 chronic SCI patients with NP (12 men, age=52.2±10.5 [y], years since injury=11.3±9.2), 10 patients without NP (10 men, age=50.0±10.3 [y], years since injury=18.4±10.5), and 21 healthy controls (HC, 18 men, age=45.0±11.9 [y]). All participants underwent MRS measurement on a 3T scanner (Philips, Netherlands) with a 16 channel SENSE neurovascular coil. T2-weighted images (0.5x0.5x3.2 mm3) were used to place the spectroscopic voxel (6x9x35 mm3) at spinal level C2 and the metabolite cycling (MC) technique [5] was applied. Each MRS measurement contained 512 signal averages and the data were fitted using LCModel [6]. MRS allowed us to reliably detect total N-Acetyl-Aspartate (tNAA), choline containing compound (tCho), and myo-Inositol (mI) at cervical level (CRLB<25%). Groups were compared regarding their tNAA/mI and tCho/mI ratios. All patients were clinically assessed using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol for light-touch and pin-prick scores [7]. Statistical analyses were performed using R (R Core Team, 2016, Version 3.4.3). Group differences were assessed with the Kruskal-Wallis test and Spearman's rank correlations were used to investigate associations between metabolic ratios and clinical outcome. Results with an uncorrected p-value ≤ 0.05 were regarded as significant.

Results:

We found lower tNAA/mI (P=0.005) and tCho/mI (P=0.002) ratios in chronic SCI patients without NP compared to HC (Fig. 1). Additionally, tCho/mI was lower in SCI patients without NP in comparison to patients with NP (P=0.024). However, in patients with NP, tCho/mI and tNAA/mI were at a similar level as in HC. As shown in Fig. 2, the tCho/mI ratio was positively associated with pin-prick (P=0.006, R2=0.298) and light-touch (P=0.001, R2=0.381) scores.
Supporting Image: OHBM_2019_Pfyffer_Figure1.png
Supporting Image: OHBM_2019_Pfyffer_Figure2_.png
 

Conclusions:

This study shows that chronic SCI patients without NP had decreased tNAA/mI and tCho/mI ratios compared to HC and lower tCho/mI ratios compared to patients with NP. Reductions of these ratios can either result from an increase of mI (marker for reactive gliosis and neuro-inflammation) or a decrease in tNAA (neuronal cell integrity marker) and tCho (marker for cell membrane turnover), or both. Thus, our findings could point towards either ongoing neuro-inflammation or neurodegeneration in patients without NP, or both. Patients with NP, on the other hand, are likely to have more spinothalamic tract-specific viable neurons mediating NP and therefore more closely resemble HC. Worse clinical outcome measures were associated with lower tCho/mI ratios, likely originating from reactive astrocytes counteracting axonal regeneration and mediating the clinical impairment [8]. In conclusion, sensitive MRS at the cervical cord can provide metabolic biomarkers underlying neurodegenerative changes and neuro-inflammation after SCI which have the potential to be used in clinical trials for patient stratification and therapy monitoring.

Disorders of the Nervous System:

Disorders of the Nervous System Other 1

Imaging Methods:

MR Spectroscopy 2

Neuroanatomy:

Anatomy and Functional Systems

Perception and Attention:

Perception: Pain and Visceral
Perception: Tactile/Somatosensory

Keywords:

DISORDERS
Magnetic Resonance Spectroscopy (MRS)
Pain
Somatosensory
Spinal Cord
Other - Spinal Cord Injury; Neuropathic Pain; Metabolites; Neurodegeneration; Neuro-Inflammation

1|2Indicates the priority used for review

My abstract is being submitted as a Software Demonstration.

No

Please indicate below if your study was a "resting state" or "task-activation” study.

Resting state

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Patients

Was any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Was any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Other, Please specify  -   Magnetic Resonance Spectroscopy (MRS)
Behavior

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

Other, Please list  -   LCModel

Provide references using author date format

de Graaf, R. A. (2007). In Vivo NMR Spectroscopy', John Wiley & Sons. [2]
Freund, P. (2011). 'Disability, atrophy and cortical reorganization following spinal cord injury', Brain, 134: 1610-22. [1]
Gustin, S. M. (2014). 'Thalamic activity and biochemical changes in individuals with neuropathic pain after spinal cord injury', Pain, 155: 1027-36. [3]
Hock, A. (2013). 'Non-water-suppressed proton MR spectroscopy improves spectral quality in the human spinal cord', Magnetic Resonance in Medicine, 69: 1253-60. [5]
Kirshblum, S. C. (2011). 'International standards for neurological classification of spinal cord injury (revised 2011)', The Journal of Spinal Cord Medicine, 34: 535-46. [7]
Provencher, S. W. (1993). 'Estimation of metabolite concentrations from localized in vivo proton NMR spectra', Magnetic Resonance in Medicine, 30: 672-9. [6]
Stanwell, P. (2010). 'Neuro magnetic resonance spectroscopy using wavelet decomposition and statistical testing identifies biochemical changes in people with spinal cord injury and pain', Neuroimage, 53: 544-52. [8]
Widerstrom-Noga, E. (2013). 'Metabolite concentrations in the anterior cingulate cortex predict high neuropathic pain impact after spinal cord injury', Pain, 154: 204-12. [4]