Objective: To quantify the longitudinal evolution of metabolic indicators of gliosis and neuronal integrity in patients with multiple system atrophy (MSA) over one year.

Background: MSA is pathologically characterized by glial cytoplasmic inclusions, neuronal loss, axonal degeneration, microglial activation and astrogliosis in the basal ganglia. Early diagnosis of MSA is vital for maximizing neuronal preservation with disease modifying therapies, and thus identifying biomarkers for early pathology is critical. Magnetic resonance spectroscopy (MRS) is a non-invasive technique that allows for metabolite quantification, including myoinositol (a marker of gliosis) and N-acetylaspartate (NAA; a marker of neuronal integrity). We applied MRS longitudinally to test the hypothesis that these neuro-chemical biomarkers are associated with clinical indicators of disease severity in MSA.

Method: Participants underwent 3T MRS and completed neurologic examination including clinical assessment with the Unified Multiple System Atrophy Rating Scale (UMSARS) and Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS) rating scales at baseline, 6 months, and 12 months. MRS was obtained from the right putamen using a PRESS sequence. Data processing was performed using Osprey, and the tissue-corrected water-scaled myoinositol (mI/water) and NAA (NAA/water) estimates were obtained. Spearman correlation was used to evaluate the relationships between metabolite concentration and clinical scores. Wilcoxon signed-rank test was used to compare the results between baseline and follow up.

Results: 13 early MSA patients (Age=60±8 years; symptom onset < 4 years) were assessed at baseline; 10 patients completed the 6-month visit and 8 patients completed the 12-month visit. mI/water was significantly positively associated with UMSARS (p=0.41, 0.01, and 0.03 for baseline, 6-month, and 12-month follow-up) and NNIPPS (p=0.20, 0.03, and 0.03). Similarly, NAA/water trended inversely with these clinical scores, but these relationships were statistically non-significant.

Conclusion: We provide evidence that mI/water increases, while NAA/water decrease over one-year in patients with MSA, suggesting that metabolite concentration by MRS may be useful biomarkers for assessing disease severity and treatment response in early MSA.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/preliminary-evidence-for-evolution-of-myoinositol-and-n-acteylaspartate-as-biomarkers-of-disease-severity-in-early-stage-multiple-system-atrophy/