Increased Sodium Concentration in Substantia Nigra in Early Parkinson's Disease: A Preliminary Study With Ultra-High Field (7T) MRI

Abstract

Pathophysiology of idiopathic Parkinson's disease (iPD) is complex and still misunderstood. At a time when treatments with disease-modifying potential are being developed, identification of early markers of neurodegeneration is essential. Intracerebral sodium accumulation could be one of them. Indeed, it may be in relation to the mitochondrial dysfunction that early exists in iPD. For the first time, we used brain sodium (23Na) MRI to explore sodium concentration changes that have already been reported to be related to neurodegeneration in other diseases. We prospectively included 10 iPD patients (mean age 52.2 ± 5.9 years-old) with motor symptoms that started <36 months before inclusion and 12 healthy subjects (mean age 53 ± 6.4 years-old). Patients were scanned in OFF medication state by using proton (1H) and 23Na MRI at 7T. We then extracted quantitative Total Sodium Concentration (TSC) from five regions of interest known to be early impaired in iPD [substantia nigra (SN), putamen, caudate nucleus, pallidum, thalamus] and in one region supposed to be relatively spared in the first stages of the disease [cortical gray matter (neocortex)]. Potential atrophy in these structures was also investigated with 1H MRI. Relative to healthy subjects, iPD patients showed higher TSC in the SN (43.73 ± 4.64 vs. 37.72 ± 5.62, p = 0.006 after Bonferroni correction). A trend of increase in sodium concentrations was found within the pallidum (45.80 ± 4.19 vs. 41.07 ± 4.94, p = 0.017), putamen (48.65 ± 4.58 vs. 43.66 ± 5.04, p = 0.041) and the cortical gray matter (56.34 ± 3.92 vs. 50.81 ± 5.50, p = 0.021). No significant brain atrophy was found in patients compared to controls. Thus, alteration of sodium homeostasis in the SN in the absence of atrophy could be considered as a potential early marker of cellular dysfunction in iPD.

Increased Subcortical Sodium Levels in Patients with Progressive Supranuclear Palsy

“…In a recent study applying high-field 23 Na-MRI, similar changes were demonstrated in the midbrain of patients with Parkinson’s disease. Comparative studies are therefore needed to investigate whether observed changes are specific to distinct Parkinsonian disorders [ 13 ].…”

“…Besides some disadvantages, 23 Na-MRI will provide deepened insights into specific disease mechanisms and can help in complimentary map neurodegeneration in vivo. However, the combination with other, in particular pathophysiology-orientated, neuroimaging modalities would be desirable to further enhance the biological interpretability of our findings [ 13 ]. Future studies in larger cohorts are necessary to ensure the reproducibility of our findings.…”

Combining Sodium MRI, Proton MR Spectroscopic Imaging and Intracerebral EEG in Epilepsy

“…The 23 Na-MRI data were processed according to (Grimaldi et al, 2021) using a homemade adjusted procedure. After brain extraction on ²³Na-MRI images (ANTS, (Avants et al, 2011)), a denoising filter was applied to the resulting 23 Na-MRI volumes (Aja-Fernandez et al, 2008; Rajan et al, 2010).…”

Comprehensive Account of Sodium Imaging and Spectroscopy for Brain Research

“…Patients with AD have also shown a significant increase in the tissue sodium Figure 6. Brain disorders exhibiting abnormal sodium concentration levels during 23 Na imaging with the disease progression including AD, 77,82 brain tumor, 42,83 epilepsy, 84 MS, 85 cerebral ischemia 86 Friedreich's ataxia, 87 Huntington's disease, 88 glioblastoma, 89 Parkinson's disease, 90 stroke, 91 migraine, 92 and cerebral hemorrhage. volume in the amygdala, hippocampus, and WM as compared to healthy controls, which denotes neuronal loss.…”

“…Brain disorders exhibiting abnormal sodium concentration levels during 23 Na imaging with the disease progression including AD, , brain tumor, , epilepsy, MS, cerebral ischemia Friedreich’s ataxia, Huntington’s disease, glioblastoma, Parkinson’s disease, stroke, migraine, and cerebral hemorrhage …”