P14. Sodium magnetic resonance imaging in Friedreich ataxia – A preliminary study

Abstract

Friedreich ataxia (FRDA) is the most common autosomal recessive inherited ataxia, mainly caused by a GAA trinucleotide repeat expansion in the FRDA gene encoding the protein frataxin (Bradley et al., 2000). Magnetic resonance imaging (MRI) has successfully been used to detect abnormalities in the brainstem, cerebellum and cortex in FRDA ([Franca et al., 2009], [Dogan et al., 2016]). Here, we used in vivo sodium MRI to investigate cerebral metabolic changes in FRDA (Reetz et al., 2012). Can sodium MRI provide a deeper insight into the metabolic pathophysiology in FRDA? Is the total sodium concentration (TSC) in brain tissue of FRDA patients higher than of controls?. We studied 11 FRDA patients (6 females; mean age = 36.36 [12.55]) and 8 healthy controls (7 females; mean age = 32.88 [8.92]). We estimated the TSC in the cerebellar white matter (left and right CWM) and in the brainstem from sodium MRI acquired on a 3 Tesla whole-body MR scanner (PRISMA, Siemens Medical Systems, Erlangen). Total scan time was 20 min, isotropic resolution 4 mm3. Clinically, we assessed the major symptom ataxia with the Scale for the Assessment and Rating of Ataxia (SARA) (Reetz et al., 2016). One-tailed Student’s t-test was used for mean TSC between groups. Pearson correlation was conducted between mean TSC and SARA scores, age, age of onset, disease duration as well as GAA repeats of both alleles in FRDA patients. In FRDA patients we found ahigher TSC in the left CWM (mean [M] = 45.77, standard error [SE] = .71) and in the brainstem (M = 46.76, SE = 1.03) in comparison to controls (left CWM [M = 43.40, SE = .75; t[17] = −2.27], brainstem [M = 43.70, SE = .97; t[17] = −2.09]; both p<.05). In the right CWM, there were marginally significant higher TSC levels in patients (M = 45.05, SE = .81) than in controls (M = 43.55, SE = .59; t[16.68] = −1.49, p<.10). A positive relationship was found between SARA scores and TSC in all three brain areas (left CWM [r = .50,p<.10], right CWM [r = .66, p<.05], brainstem [r = .65, p<.05]). Remaining correlations gained no significance (p>.05). The increase of TSC in cerebellum and brainstem in FRDA patients suggests the diagnostic potential of in vivo sodium MRI to differentiate between patients and controls. Moreover, this was related to more severe ataxia, as assessed by the SARA. These preliminary results support our hypothesis that sodium MRI may be a new imaging marker that could shed new insights into the metabolic pathophysiological mechanisms of FRDA.