Tract-based spatial statistics of the olfactory brain in patients with multiple sclerosis
Introduction
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system resulting in demyelination. Magnetic resonance imaging (MRI) is useful in detecting MS-typical lesions; however, the poor association between clinical extent and radiological visible involvement was discussed previously [1]. It was suggested that the so-called normal-appearing brain tissue (NABT) is affected by the disease too [2]. Diffusion tensor imaging (DTI) measures the Brownian motion of water molecules and its directional prevalence. The directional prevalence is reduced in MS lesions as well as in NABT [3]. This reduced directionality of water motion can be quantified as fractional anisotropy (FA; 1 indicating exclusive diffusion in one direction, 0 indicating no preferred direction of diffusion). Many studies have used FA as a marker for assessing the integrity of neuronal tissue in MS patients. A decreased FA is inherently coupled to an increased mean diffusivity (MD) and an increased radial diffusivity (RD) due to the reduced directionality.
There is evidence that MS patients can experience alterations in olfactory function in the course of the disease [4], [5]. Zivadinov et al. report an impaired olfactory function in a considerable number of MS patients as well as a low level of awareness of patients having episodes of smell loss [6]. Previously, it has been discussed whether olfactory impairment is an early hallmark of the disease [7]. However, it seems that especially those aspects of olfactory function are affected which require higher cognitive involvement such as discrimination and identification of odours [8]. It has been reported that the frequency of odour identification impairment was higher for patients with secondary progressive than relapsing–remitting or primary progressive courses [9]. Previous studies indicate that impaired olfactory function correlates with the lesion load in the olfactory brain [10], [11], [12], [13].
However, none of the studies attempted to describe diffusion abnormalities in the entire olfactory brain of MS patients.
Tract-based spatial statistics (TBSS) was developed for voxelwise analysis of DTI data and comparison in multi-subject studies [14], [15]. The software allows assessing streamlines in brain structures from the diffusion tensor data. Furthermore, it allows determining the number of streamlines outgoing from a seed point or structure. Threshold-free cluster enhancement (TFCE) cluster analysis uses spatial neighbourhood information from perpendicular voxels to enhance information on the spatial distribution of lesions in white matter pathways [16]. TBSS-based analysis of multiple sclerosis patients indicates that FA is lower in a number of brain regions and has been shown to be useful to localise damage [17].
In this study we used TBSS to determine FA, MD, and RD changes of the olfactory brain of MS patients.
We hypothesised that FA is reduced in patients with impaired olfactory function and quantified clusters with significantly decreased FA in the olfactory brain using MNI coordinates. To check for differences between MS patients and healthy controls we also compared reconstructed streamlines outgoing from the olfactory brain in both groups.
Section snippets
Material and methods
For this prospective study, we recruited 30 patients and 12 healthy volunteers for MRI measurements. Our own database of normal olfactory function consisting of a reference group of 30 healthy volunteers was used to compare olfactory performance.
All patients fulfilled the McDonald criteria for MS and were between 18 and 65 years old [18]. All patients underwent neurological examination on the day of magnetic resonance imaging (MRI). Furthermore, they were seen by an ENT specialist for
Results
The groups (patient group, n = 30; MRI healthy controls, n = 12; database consisting of a reference group for olfactory testing, n = 30) were compared for age.
The groups did not differ in mean age (patients 40.7 ± 11.7 years; MRI healthy volunteers 38.3 ± 11.9 years, p > 0.05; reference group for olfactory testing 42.4 ± 12.3, p > 0.05).
Clinical characteristics (disease duration, EDSS, BDI, MMSE) of patients as well as demographic data of the healthy controls and olfactory test results of the reference group are
Discussion
Our results indicate that there are significant differences in DTI data volumes of the olfactory brain of MS patients compared to healthy controls. The main finding of this study is that there is a significant decrease in FA in central olfactory structures of MS patients compared to healthy controls. The FA decrease and MD/RD increase become more marked if correlated with the I subscore. The location of the FA decreased cluster differs between group comparison and correlation with the I
Conflict of interest
The authors have no conflict of interest to disclose.
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