Sodium accumulation in brain correlates with MS progression

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Sodium accumulation in brain correlates with MS progression

Postby Anonymoose » Fri Mar 15, 2013 8:43 am

Aldosterone secretion (part of hpa axis dysregulation in RRMS) increases sodium retention and upregulates sodium channels. ... KEN_ID=900
Brain sodium accumulation and spreading correlate with disability in multiple sclerosis

W. Zaaraoui, B. Audoin, S. Konstandin, A.M. Nagel, E. Soulier, I. Malikova, A. Rico, F. Reuter, P. Viout, S. Confort-Gouny, P.J. Cozzone, J. Pelletier, L.R. Schad, J.-P. Ranjeva (Marseille, FR; Mannheim, Heidelberg, DE)
Purpose: Recent histopathological studies have highlighted the potential key role of sodium accumulation that leads to neuronal injury in multiple sclerosis (MS). We aimed to quantify brain sodium accumulation and characterize for the first time the spatial location of sodium abnormalities at different stages of relapsing remitting multiple sclerosis (RRMS) using sodium MRI.
Materials and Methods: MR explorations were performed at 3T (Verio, Siemens) in two groups of RRMS patients, 14 early RRMS (disease duration<5years) and 12 advanced RRMS (>5years) and 15 controls. Sodium 23Na MRI was acquired using a double-tuned 23Na-1H volume head coil (RapidBiomed) and a density-adapted 3D radial projection reconstruction pulse sequence (Nagel et al 2009) (TE=200µs, TR=120ms, 17000 projections, resolution 3.6x3.6x3.6 mm3) with two external references. Proton MRI 3D-MPRAGE (resolution 1x1x1mm3) and T2-weighted were also obtained. The post-processing included reconstruction of the quantitative 3D radial sodium images (q23Na-MRI); coregistration of the q23Na-MRI with 1H-3D-MPRAGE; normalization and segmentation of the 1H-3D-MPRAGE (VBM8); application of the resulting grey matter (GM), white matter (WM) and T2-lesions masks to the normalized q23Na-MRI; smoothing of the resulting q23Na-MRI maps and statistical mapping analysis (SPM8) to locate total sodium concentration (TSC) abnormalities.
Results: For the two groups of MS patients, TSC was increased inside demyelinating lesions while increased TSC was observed in normal appearing WM and GM only in advanced RRMS. In patients, increased TSC inside GM was correlated to disability (EDSS) (p=0.046) and T2 lesion load (p=0.003) but not to disease duration (p=0.089). Statistical mapping analysis (SPM8, Anova, p<0.001) showed that abnormal TSC are already present at the early stage of RRMS in limited regions (brainstem, cerebellum and temporal poles) and are widespread, affecting the whole brain parenchyma, at the advanced stage of RRMS. EDSS was correlated to TSC increases inside a coherent motor network including bilateral cerebellum, primary motor area and bilateral prefrontal cortices (SPM8, simple regression, p<0.001).
Conclusions: Total sodium accumulation dramatically increases in advanced stage of RRMS especially in the normal appearing brain tissues concomitantly to disability. Further brain sodium MRI longitudinal studies with more patients are required to help monitoring the occurrence of tissue injury and disability.
Last edited by Anonymoose on Fri Mar 15, 2013 8:54 am, edited 1 time in total.
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Re: Sodium accumulation in brain correlates with MS progress

Postby Anonymoose » Fri Mar 15, 2013 8:49 am

Sodium buildup in motor areas of brain correspond directly with motor dysfunction. ... disability
Sodium buildup in the brain correlates with MS disability

By Lisa FrattJul 16, 2012

Images in 33-year-old man with early RR MS. Examples of substantial sodium accumulation in two macroscopic T2 lesions with two different signal intensity patterns at T1-weighted imaging: one lesion was hypointense (solid arrows) and one was isointense (dashed arrows) to normal-appearing WM on T1- weighted image. Source: Radiology (Zaaraoui et al)
A buildup of sodium in the brain detected by MRI may be a biomarker for the degeneration of nerve cells that occurs in patients with multiple sclerosis (MS), according to a study published online in Radiology.

Several key findings emerged from the study. The researchers found that patients with early-stage MS showed sodium accumulation in specific brain regions, while patients with more advanced disease showed sodium accumulation throughout the whole brain, including in normal-appearing areas. Sodium buildup in motor areas of the brain correlated directly to the degree of disability seen in the advanced-stage patients.

“A major challenge with multiple sclerosis is providing patients with a prognosis of disease progression,” Patrick Cozzone, PhD, director emeritus of the Center for Magnetic Resonance in Biology and Medicine, in Marseille, France, said in a release. “It’s very hard to predict the course of the disease.”

Experimental studies have suggested sodium accumulation may play a part in the development of neuronal injury that is the hallmark of MS. Thus, Cozzone and colleagues used 3T sodium MRI to study relapsing-remitting multiple sclerosis (RRMS).

The researchers conducted sodium MRI on 26 MS patients—14 with early-stage RRMS (less than five years in duration) and 12 with advanced disease (longer than five years)—as well as 15 age- and sex-matched control participants.

Cozzone and colleagues completed quantitative assessments of total sodium concentration (TSC) levels within MS lesions, white matter and gray matter.

In the early-stage RRMS patients, sodium MRI revealed abnormally high concentrations of sodium in specific brain regions, including the brainstem, cerebellum and temporal pole. “The early preferential susceptibility of these regions may be related to their high degree of connectivity, which increases their vulnerability to distant axonal injury.” In the advanced-stage RRMS patients, abnormally high sodium accumulation was widespread throughout the whole brain, including normal-appearing brain tissue.

Specifically, TSC values in normal-appearing white matter among participants with advanced MS were significantly higher than in control subjects. In the gray matter compartment, advanced patients also had significantly higher TSC values than those with early MS, which may reflect neuronal loss and neuronal dysfunction, according to the researchers. These values also were higher relative to control subjects for patients with advanced disease, but not those with early disease.

Because current treatments for MS are only able to slow the progress of the disease, the use of sodium accumulation as a biomarker of neuron degeneration may assist pharmaceutical companies in developing and assessing potential treatments. The method also may help monitor the occurrence of tissue injury and disability, according to Cozzone et al.

“Indeed, the results of this cross-sectional study must be confirmed in a larger group of patients and longitudinal follow-up studies are needed to better depict and understand the patterns of brain sodium accumulation and their clinical impact during the course of MS,” wrote Cozzone and colleagues.
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