Objective: The primary objective was to compare brain 5-HT1a receptor binding between patients with multiple system atrophy (MSA) and healthy controls (HC). The secondary objectives were (i) to compare brain 5-HT1a receptor binding between MSA and Parkinson’s disease (PD) patients and (ii) to assess potential associations between brain 5-HT1a receptor binding and motor/non-motor symptoms in MSA patients.

Background: Post-mortem studies have demonstrated a significant loss of brain serotonin neurons in MSA patients. More specifically, a depletion of medullary serotonergic neurons has been linked to respiratory disturbances and sudden death. It is very likely that the loss of serotonin function also contributes to other symptoms in MSA, such as mood disorders, sleep disturbances and fatigue.

Method: [¹⁸F]-MPPF PET was used to assess 5-HT1a receptor expression in several predefined brain regions in age and sex-matched patients with MSA (n=16), PD (n=15) and HC (n=18).  The dynamic PET image series was quantitatively analysed using the Logan Plot kinetic model (cerebellum as reference region), giving access to the [¹⁸F]-MPPF non-displaceable binding potential (BP_ND) in 19 cerebral regions (delineation performed using the Freesurfer software). MSA and PD patients were further matched for disease duration. Symptom severity was determined by validated rating scales. Comparisons used adjusted linear regression on age, gender and disease duration. Association with scales used Spearman correlation coefficient and Student test.

Results: [¹⁸F]-MPPF BP_ND were lower in MSA patients compared to HC in caudate nucleus (0.61 vs 0.70 [-0.13;-0.04], p<0.0001), raphe nucleus (0.98 vs 1.19 [-0.21;-0.10], p<0.0002), thalamus (0.81 vs 0.86 [-0.09;-0.02], p<0.0022), and brain stem (0.89 vs 0.95 [-0.08;-0.02], p<0.0002). BP_ND were also lower in the brain stem in MSA compared to PD patients (0.89 vs 0.93 [-0.08;-0.01], p<0.0063). MSA patients showed moderate correlations between BP_ND in the raphe nucleus and fatigue (-0.43 [-0.71;0.03]) and pain (-0.40 [-0.77;0.15]). UMSARS II scores, mood, apathy, daytime sleepiness, and sleep quality showed no or only weak correlations with raphe BP_ND.

Conclusion: Our results demonstrate impaired serotonergic neurotransmission in several brain regions in MSA patients compared to HC and PD patients. They further suggest that impaired serotonergic brain function may contribute to fatigue and pain in MSA patients.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/brain-5-ht1-receptor-binding-in-multiple-system-atrophy-a-18f-mppf-pet-study/