THU0324 AXONAL DYSFUNCTION IN CEREBRAL WHITE MATTER IN SYSTEMIC SCLEROSIS: A PROTON MAGNETIC RESONANCE SPECTROSCOPIC IMAGING (¹H-MRSI) STUDY
Authors: Danilo Pereira, Mariana Freschi, Renan Frittoli, Tiago Amaral, Sergio Dertkigil, Ana Paula del Rio, Gabriela Castellano, Fernando Cendes, Leticia Rittner, Simone Appenzeller
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic sclerosis (SSc) is a diffuse connective tissue disease characterized by varying degrees of cutaneous and visceral fibrosis, presence of autoantibodies and vasculopathy. In addition, central nervous system (CNS) involvements are often observed [1]. <h3>Objectives:</h3> The aim of the present study was to investigate the presence of axonal dysfunction in systemic sclerosis (SSc) and to determine if clinical, laboratory and treatment features are associated with its occurrence. <h3>Methods:</h3> In this longitudinal study we included 38 SSc patients (32 woman, mean age of 50.86, SD±11.66 years; range 31- 74) and 38 healthy volunteers (32 woman, mean age of 49.23, SD±12.03 years; range 26 - 77). All individuals were evaluated (neuropsychiatric evaluation and MRI) at study entry and after 12 months. Cognitive evaluation was performed using the Montreal Cognitive Assessment (MoCA), mood disorders were determined through Beck's Depression (BDI) and Beck's Anxiety Inventories (BAI). Individual with scores: MoCA ≤26, BDI ≥11 and BAI ≥7 were considered impaired. SSc patients were further assessed for clinical and laboratory SSc manifestations, disease activity (Valentini Activity Index), severity activity (Medsger Severity Index). We performed multi-voxel ¹H-MRSI over the superior-posterior region of the corpus callosum. Our MRI/MRSI protocol consisted of: T1-weighted images; 2D pulse sequence (PRESS); excitation angle of 90°; Long TE: 144ms and TR: 2000ms; VOI (MRSI) size (mm) ≈ (116 x 79 x 16) grid with 208 spectra. Scans were performed with a Philips 3.0T MRI scanner. We measured signals from <i>N</i>-acetyl-compounds (NAA), creatine (Cr), choline (Cho), glutamate (Glu), glutamine (Gln) and Glx (the sum of Glu and Gln) using TARQUIN software. Statistics was performed according nature of the variable. <h3>Results:</h3> We observed a significant reduction in NAA/Cr (mean value=1.72; SD=2.4) and Cho/Cr (mean value=2.4; SD=2.04) ratio in SSc when compared to controls (NAA/Cr mean value=1.85; SD=2.7; p = 0.36; Cho/Cr mean value=0.377; SD=0.169; p&lt;0.001). Reduction in NAA/Cr ratio was associated with cognitive impairment (p = 0.017), presence of migraine (p = 0.001), current use of prednisone (p=0.010) and current use of methotrexate (p &lt; 0.001). NAA/Cr ratio correlated with MOCA scores (r=0.4; p=0,015). Follow up study showed a reduction in NAA/Cr values when compared to patients' baseline values (p = 0.0341). <h3>Conclusion:</h3> Our results showed a significant reduction in NAA/Cr ratio in SSc patients associated with cognitive impairment and the use of some drugs (MTX and prednisone) during the treatment. Therefore, NAA/Cr ratios may be a useful biomarker in follow-up studies of SSc. <h3>References:</h3> [1] Hietaharju A, Jaaskelainen S, Hietarinta M, Frey H. Central nervous system involvement and psychiatric manifestations in systemic sclerosis (scleroderma): clinical and neurophysiological evaluation. Acta neurologica Scandinavica. 1993 [2] Mountford, C. E., Stanwell, P., Lin, A., Ramadan, S., and Ross, B., Neurospectroscopy: the past, presente and future," Chemical reviews, 2010 [3] Wilson, M., Reynolds, G., Kauppinen, R. A., Arvanitis, T. N., and Peet, A. C., A constrained least-squares approach to the automated quantitation of in vivo 1h magnetic resonance spectroscopy data," Magnetic resonance in medicine, 2011. <h3>Disclosure of Interests:</h3> None declared