Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation-Related Mild Ischemic Stroke: A Randomized Clinical Trial.

Importance: In atrial fibrillation (AF)-related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear. Objective: To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke. Design, Setting, and Participants: A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis. Interventions: Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks. Main Outcomes and Measures: The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length. Results: Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001). Conclusions and Relevance: In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy. Trial Registration: clinicaltrials.gov Identifier: NCT02042534.

Altered thalamocortical functional connectivity in idiopathic generalized epilepsy.

OBJECTIVE: Aberrant thalamocortical network has been hypothesized to play a crucial role in the fundamental pathogenesis underlying idiopathic generalized epilepsy (IGE). We aimed to investigate alterations of thalamocortical functional network in patients with IGE using thalamic seed-based functional connectivity (FC) analysis, and their relationships with frontal cognitive functions and clinical characteristics. METHODS: Forty-nine IGE patients (31 with juvenile myoclonic epilepsy, 17 with IGE with generalized tonic-clonic seizures only, one with juvenile absence epilepsy) and 42 control subjects were prospectively recruited. Voxel-based morphometry (VBM) was first performed to detect thalamic region of gray matter (GM) reduction in patients compared to controls. Between-group comparison of thalamocortical FC was then carried out using resting-state functional magnetic resonance imaging (MRI) analysis seeding at thalamic region of volume difference. In addition, thalamocortical FC was correlated with frontal cognitive performance and clinical variables. RESULTS: Neuropsychological assessment revealed that patients with IGE had poorer performance than controls on most of the frontal cognitive functions. VBM detected a reduction in GM in the anteromedial thalamus in patients relative to controls. FC analysis seeding at the anteromedial thalamus revealed a reduction of thalamocortical FC in the bilateral medial prefrontal cortex and precuneus/posterior cingulate cortex in patients with IGE compared to controls. Thalamocortical FC strength of bilateral medial prefrontal cortex correlated negatively with disease duration, but did not correlate with seizure frequency or frontal cognitive functions in patients with IGE. SIGNIFICANCE: Our results indicate that IGE is associated with decreased thalamocortical FC between anteromedial thalamus and medial prefrontal cortex and precuneus/posterior cingulate cortex. Our finding of greater reduction of medial prefrontal FC in relation to increasing disease duration suggests that thalamoprefrontal network abnormality, the proposed pathophysiologic mechanism underlying IGE, may be the consequence of the long-standing burden of the disease.

Volumetric and shape analysis of thalamus in idiopathic generalized epilepsy.

Previous studies using voxel-based morphometry (VBM) provided emerging evidence of structural changes of the thalamus in idiopathic generalized epilepsy (IGE). However, the location of atrophy within the thalamus in IGE has been somewhat inconsistent across the studies. We, therefore, examined the location of thalamic atrophy and its relationship with clinical factors in IGE, using multiple analytic methods. Fifty IGE patients and 50 controls were scanned on a 3T MRI. Structural evaluation consisted of automated thalamic volumetry, VBM, and thalamic shape analysis. Group comparison between patients and controls was made to assess thalamic atrophy. Within-group correlations between thalamic atrophy and clinical variables were further performed in patients. Both thalamic volumes were reduced in IGE patients, and were negatively correlated with disease duration. The VBM showed a significant regional grey matter volume reduction in bilateral anterior-medial thalami in patients compared to controls. Voxel values extracted from the anterior-medial thalamic cluster were negatively correlated with disease duration. Vertex-based shape analysis revealed regional atrophy on the anterior-medial and posterior-dorsal aspects of thalamus bilaterally in patients compared to controls. Correlation analysis showed that anterior-medial and posterior-dorsal aspects of bilateral thalami were negatively correlated with disease duration. Combining multiple analyses, we demonstrated regional atrophy of anterior-medial and posterior-dorsal thalamus in patients with IGE. Given the anatomical connection of these thalamic regions with the frontal lobe, our finding of greater thalamic atrophy in relation to increasing disease duration further supports the pathophysiological concept of thalamo-frontal network abnormality underlying IGE, and may implicate frontal cognitive dysfunctions and disease progression.