Changes of central noradrenaline transporter availability in immunotherapy-naïve multiple sclerosis patients

Ziel/Aim The neurotransmitter noradrenaline (NA) mediates arousal, attention and mood, and exerts anti-inflammatory and neuroprotective effects. Alterations of NA signalling are assumed to account for the high prevalence of comorbid fatigue in patients with multiple sclerosis (MS). Data on in vivo NA transmission, specifically on central NA transporter (NAT), in MS patients, however, do not exist. Therefore, we aimed to assess NAT availability using PET in immunotherapy-naïve patients with relapsing-remitting MS (RRMS) compared with healthy controls (HC) and in relation to clinical and fatigue measures in the RRMS group.

Methodik/Methods PET using the NAT-selective [¹¹C]MRB was applied in 11 patients with RRMS (7 females, 38.3±9.5 yrs) who fulfilled the revised McDonald criteria of 2010 and 12 HC (6 females, 33.5±10.6 yrs). All participants were non-depressed and naïve to immunomodulatory therapy. Distribution volume ratios (DVR) using the occipital cortex as reference region were calculated as the imaging outcome parameter. Clinically, the expanded disability status scale (EDSS) and the fatigue scale Würzburger Erschöpfungsinventar bei MS (WEIMuS) were used.

Ergebnisse/Results Overall, MS patients showed higher DVR as compared with HC predominantly in thalamus (1.72±0.19 vs 1.42±0.16; p = 0.001), amygdala (1.23±0.11 vs 1.10±0.12; p = 0.014) and pons/midbrain (1.19±0.09 vs 1.05±0.06; p = 0.008). Fatigue scores were higher in MS patients compared with HC (16 [range 8 - 25] vs 2 [0 - 8]; p = 0.004) but did not correlate with DVR in any region. DVR was not related to the EDSS or disease duration.

Schlussfolgerungen/Conclusions These first data show higher NAT availability in NAT-rich subcortical brain regions particular indicating altered NA tone in in immunotherapy-naïve RRMS patients. If these changes predispose to other psychiatric symptoms such as depression or associate with disease activity under immunomodulatory treatment needs to be investigated in a larger sample longitudinally.