Asymmetrical Cerebral Mitochondrial Dysfunction Correlates With Motor Laterality in Parkinson's Disease: A 31Phosphorus Magnetic Resonance Spectroscopy Study.

BACKGROUND

31P magnetic resonance spectroscopy (31P-MRS) allows non-invasive assessment of mitochondrial function by quantifying metabolites of energy and phospholipid metabolism, but the association between these metabolic alterations and motor laterality in Parkinson's disease (PD) remains unknown.

PURPOSE: To investigate the association between mitochondrial dysfunction and motor symptom lateralization in PD using 31P-MRS.

STUDY TYPE: Retrospective.

POPULATION: 34 PD patients with left-sided predominance (LPD; 20 M/14 F), 35 PD patients with right-sided predominance (RPD; 16 M/19 F), and 43 healthy controls (HCs; 20 M/23 F).

FIELDSTRENGTH/SEQUENCE: 3T; 3D T1-weighted gradient-echo and 2D FID-based chemical shift imaging sequences.

ASSESSMENT: 31P-MRS spectra from bilateral putamen, frontal, and temporoparietal cortices were quantified for adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and phosphodiesters (PDE). Metabolite levels were corrected for cerebrospinal fluid (CSF) partial volume effects. Metabolic ratios and laterality indices (LIs) were calculated and correlated with motor symptom LIs.

STATISTICAL TESTS: General linear models, spearman's rank correlation, and receiver operating characteristic (ROC) analysis. p < 0.05 was considered statistically significant.

RESULTS

RPD patients exhibited significantly elevated ATP (0.181 ± 0.005) and reduced PCr/ATP (0.979 ± 0.033) in the left putamen compared to HCs (0.164 ± 0.004; 1.098 ± 0.030); they also showed a significantly lower frontal PDE LI (-0.069 ± 0.022), higher temporoparietal Pi LI (0.086 ± 0.039), and reduced PCr/Pi LI (-0.106 ± 0.041) relative to LPD patients (-0.019 ± 0.022; -0.075 ± 0.040; 0.047 ± 0.042). In the temporoparietal cortex, the LIs of PCr/Pi (r = 0.260), PME/PDE (r = 0.323), and Pi (r = -0.315) were significantly correlated with the LIs of UPDRS-III scores. The Pi LI in the temporoparietal cortex showed a promising ability to distinguish LPD from RPD patients (AUC = 0.709).

DATA

CONCLUSION

Asymmetrical mitochondrial dysfunction, detected by 31P-MRS, correlates with motor symptom laterality in PD. These metabolic asymmetries may serve as the underlying basis for symptom lateralization.

EVIDENCE LEVEL: 3.

TECHNICAL EFFICACY: Stage 1.