Dilated Virchow Robin spaces (dVRs) are common in febrile seizure (FS) patients. However, little is known about how dVRs affect the white matter structure in developing brains. This study aimed to characterize the anisotropy alterations in white matter associated with dVRs in simple FS children by using fractional anisotropy (FA). Through inter-group comparisons, FA was larger in simple FS with dVRs children than that in FS without dVRs and control groups. Significant positive correlations between FA and VRs count, seizure duration were found. These results suggest that dVRs can affect the structure of white matter by increasing FA values.
MATERIALS AND METHODS:
The study was approved by the local institutional review board. Written informed consents were obtained from the parents. Fifty simple FS with dVRs, 20 simple FS without dVRs, and 35 control children were evaluated retrospectively. The children with simple FS were diagnosed by two pediatric neurologists. MRI examinations were performed using a 3T scanner (Signa HDxt, GE Healthcare, Milwaukee, Wisconsin, USA) with an 8-channel head coil. We acquired T2 weighted sequence (TR/TE, 4200ms/120 ms; matrix, 256*256; slice thickness, 2.5 mm; FOV, 240 mm) and T2 FLAIR sequence (TR/TE, 8600 ms/165 ms; matrix, 288*224; slice thickness, 5 mm; FOV, 240 mm). DTI parameters were as follows: 30 gradient directions; b values = 0 and 600 s/mm2; TR/TE = 11000/69.5ms; slice thickness = 2.5 mm without spaces; FOV = 240 mm; and matrix size = 128 × 128. FMRIB software library (FSL, www.fmrib.ox.au.uk/fsl) was used for processing DTI data. FA maps were obtained after the brain extraction and the eddy current correction. Linear and non-linear image registrations were utilized for alignment of the FA maps of all subjects to a selected FA map. An averaged image of the co-registered FA maps was created as the target map. Then, FA maps of all subjects were registered to the target map. The mean FA map and mean FA skeleton were created. The aligned FA map of each subject were projected onto the mean FA skeleton (threshold = 0.15). Voxel-wise statistical analysis was performed to assess the inter-group differences in FA with the threshold-free cluster enhancement and family-wise error correction. Regional values were extracted from the areas with significant differences revealed by TBSS. Categorical variables were analyzed by using Chi-square test in the SPSS software (Version 21.0; IBM, Armonk, New York, USA). The continuous variables were analyzed by using Mann-Whitney U test. P values less than 0.05 were considered statistically significant.RESULTS
There was significant difference between simple FS with dVRs and simple FS without dVRs in seizure duration (Table 1), (P <0.001) and white blood count (WBCs), neutrophil (P=0.007), (P = 0.008) respectively (Table1). Compared with simple FS without dVRs group, no significant difference in the time between controlling the seizure and MRI scanning was found in simple FS with dVRs group (P= 0.741) (Table1). TBSS analysis demonstrates significant increased FA values for the simple FS patients with dVRs, compared with simple FS without dVRs and control groups (Figure 1 and 2). Positive significant correlations were found in terms of FA and seizure duration(P<0.0001) and VRs count (P=0.0001) (Figure 2).DISCUSSION
For simple FS patients with dVRs, FA value increased in the brain white matter (WM). Such changes of FA value may indicate maturation of WM microstructure, detailed as increased axon density, axonal diameter, directionality myelination and decreased water content6. Therefore, above changes may lead to the changes of DTI metrics in the majority of WM areas. Dilated VRs act as mass effect, compress water molecules in WM, and improve it is rearrangement order, and accelerate WM development7 extracellular fluid accumulation, decrease secondary to this mass effect, suggesting augmented diffusion anisotropy. This suggests high density of normal axons, as corroborated by increased index of the fiber density8. The contribution of this work is to provide information that frequent dVRs may be lead to FA changes in simple FS preschool children.CONCLUSION
This study provides an evidence that dVRs can affect the structure of WM by increasing FA values in simple FS children.