Jeong Min Kim

Unique Behavioral Characteristics and microRNA Signatures in a Drug Resistant Epilepsy Model

Background Pharmacoresistance is a major issue in the treatment of epilepsy. However, the mechanism underlying pharmacoresistance to antiepileptic drugs (AEDs) is still unclear, and few animal models have been established for studying drug resistant epilepsy (DRE). In our study, spontaneous recurrent seizures (SRSs) were investigated by video-EEG monitoring during the entire procedure. Methods/Principal Findings In the mouse pilocarpine-induced epilepsy model, we administered levetiracetam (LEV) and valproate (VPA) in sequence. AED-responsive and AED-resistant mice were naturally selected after 7-day treatment of LEV and VPA. Behavioral tests (open field, object exploration, elevated plus maze, and light-dark transition test) and a microRNA microarray test were performed. Among the 37 epileptic mice with SRS, 23 showed significantly fewer SRSs during administration of LEV (n = 16, LEV sensitive (LS) group) or VPA (n = 7, LEV resistant/VPA sensitive (LRVS) group), while 7 epileptic mice did not show any amelioration with either of the AEDs (n = 7, multidrug resistant (MDR) group). On the behavioral assessment, MDR mice displayed distinctive behaviors in the object exploration and elevated plus maze tests, which were not observed in the LS group. Expression of miRNA was altered in LS and MDR groups, and we identified 4 miRNAs (miR-206, miR-374, miR-468, and miR-142-5p), which were differently modulated in the MDR group versus both control and LS groups. Conclusion This is the first study to identify a pharmacoresistant subgroup, resistant to 2 AEDs, in the pilocarpine-induced epilepsy model. We hypothesize that modulation of the identified miRNAs may play a key role in developing pharmacoresistance and behavioral alterations in the MDR group.

Intracranial plaque enhancement from high resolution vessel wall magnetic resonance imaging predicts stroke recurrence

Background Intracranial atherosclerosis is associated with frequent stroke recurrence. High resolution vessel wall magnetic resonance imaging (HRMRI) can provide atheroma information related to its vulnerability. Aims We performed HRMRI in stroke patients with intracranial atherosclerosis to determine whether plaque characteristics from vessel wall imaging can predict future stroke recurrence. Methods Between July 2011 and June 2013, acute stroke patients with symptomatic intracranial atherosclerosis were prospectively enrolled and 3-tesla HRMRI was performed on the relevant artery. The plaque enhancement was visually determined from T1 post-gadolinium enhancement image. Stroke recurrence was monitored after index event and multivariate Cox proportional hazards model was constructed to identify factors related to future stroke recurrence. Results A total of 138 patients were included with a median follow-up of 18 months. There were 39 stroke recurrences. Plaque enhancement was detected in 108 patients (78.3%), and 37 of them experienced stroke recurrence. Among 30 stroke patients without plaque enhancement, two patients experienced stroke recurrence. Kaplan–Meier curves demonstrated a significant difference in event free survival between the patients with plaque enhancement and those patients without plaque enhancement (event rates at year 1: 30.3% vs. 6.8%, log-rank test, p = 0.004). Multivariate Cox-regression analysis showed that the plaque enhancement from HRMRI was independently associated with stroke recurrence (hazard ratio: 7.42, 95% confidence interval: 1.74–31.75, p = 0.007). Conclusion Intracranial plaque enhancement from HRMRI is associated with stroke recurrence among the patients with symptomatic intracranial atherosclerosis.

Utility of digital subtraction angiography-based collateral evaluation in medically treated acute symptomatic basilar artery stenosis.

Although a stroke from atherosclerosis in the basilar artery (BA) often presents with mild initial stroke severity, it has heterogeneous clinical courses. We investigated the efficacy of digital subtraction angiography (DSA)‐based collateral perfusion evaluation in association with long‐term outcomes of medically treated symptomatic basilar artery stenosis.