Longitudinal Effects of Bumetanide on Neuro-Cognitive Functioning in Drug-Resistant Epilepsy

Antiepileptic drugs (AEDs) have repeatedly shown inconsistent and almost contradictory effects on the neurocognitive system, from substantial impairments in processing speed to the noticeable improvement in working memory and executive functioning. Previous studies have provided a novel insight into the cognitive improvement by bumetanide as a potential antiepileptic drug. Through the current investigation, we evaluated the longitudinal effects of bumetanide, an NKCC1 co-transporter antagonist, on the brain microstructural organization as a probable underlying component for cognitive performance. Microstructure assessment was completed using SPM for the whole brain assay and Freesurfer/TRACULA for the automatic probabilistic tractography analysis. Primary cognitive operations including selective attention and processing speed, working memory capacity and spatial memory were evaluated in 12 patients with a confirmed diagnosis of refractory epilepsy. Participants treated with bumetanide (2 mg/ day) in two divided doses as an adjuvant therapy to their regular AEDs for 6 months, which followed by the re-assessment of their cognitive functions and microstructural organizations. Seizure frequency reduced in eight patients which accompanied by white matter reconstruction; fractional anisotropy (FA) increased in the cingulum-cingulate gyrus (CCG), anterior thalamic radiation (ATR), and temporal part of the superior longitudinal fasciculus (SLFt) in correlation with the clinical response. The voxel-based analysis in responder patients revealed increased FA in the left hippocampus, right cerebellum, and right medial temporal lobe, while mean diffusivity (MD) values reduced in the right occipital lobe and cerebellum. Microstructural changes in SLFt and ATR accompanied by a reduction in the error rate in the spatial memory test. These primary results have provided preliminary evidence for the effect of bumetanide on cognitive functioning through microstructural changes in patients with drug-resistant epilepsy

Symmetry differences of structural connectivity in multiple sclerosis and healthy state

Focal and diffuse cerebral damages occur in Multiple Sclerosis (MS) that promotes profound shifts in local and global structural connectivity parameters, mainly derived from diffusion tensor imaging. Most of the reconstruction analyses have applied conventional tracking algorithms largely based on the controversial streamline count. For a more credible explanation of the diffusion MRI signal, we used convex optimization modeling for the microstructure-informed tractography2 (COMMIT2) framework. All multi-shell diffusion data from 40 healthy controls (HCs) and 40 relapsing-remitting MS (RRMS) patients were transformed into COMMIT2-weighted matrices based on the Schefer-200 parcels atlas (7 networks) and 14 bilateral subcortical regions. The success of the classification process between MS and healthy state was efficiently predicted by the left DMN-related structures and visual network-associated pathways. Additionally, the lesion volume and age of onset were remarkably correlated with the components of the left DMN. Using complementary approaches such as global metrics revealed differences in WM microstructural integrity between MS and HCs (efficiency, strength). Our findings demonstrated that the cutting-edge diffusion MRI biomarkers could hold the potential for interpreting brain abnormalities in a more distinctive way