Risk of seizure relapse after antiepileptic drug withdrawal in adult patients with focal epilepsy.

OBJECTIVE: The objective of this study was to estimate the risk of a seizure relapse and the high-risk period of recurrence after antiepileptic drug (AED) withdrawal and to determine the predictive factors for a seizure relapse in adult patients with focal epilepsy who were seizure-free for more than 2years. METHODS: Using the Wenzhou Epilepsy Follow-Up Registry Database, 200 adult patients with focal epilepsy were recruited, who were undergoing follow-up, met the inclusion criteria of this study, were seizure-free for more than 2years, began withdrawing between June 2003 and June 2014, and were followed up prospectively for at least 1year or until a seizure relapse. The risk of recurrence and the time to seizure relapse were analyzed by the Kaplan-Meier method, and the predictive factors were identified by the Cox proportional hazard regression model. RESULT: A total of 99 patients had an unprovoked relapse during the follow-up period. The relapse rate was 49.5%, and each year, the recurrence probability of 12, 24, 36, 48, 60, 72, and 84months after AED withdrawal was 24.0%, 20.4%, 8.3%, 2.7%, 4.6%, 0.97%, and 0.98%, respectively. The two independent risk factors for recurrence after withdrawal in adult patients with focal epilepsy were a longer duration of active epilepsy and a shorter seizure-free period before withdrawal. CONCLUSION: The high-risk period of a seizure relapse in adult patients with focal epilepsy is the first 2years after withdrawal, and beyond 5years after withdrawal, seizures rarely relapse (relapse rate<1%). A seizure-free period for less than 4years before withdrawal is a predictive factor of risk for seizure recurrence after AED withdrawal in adult patients with focal epilepsy.

Progressive Collapse Safety Evaluation of Truss Structures Considering Material Plasticity.

Theoretical or numerical progressive collapse analysis is necessary for important civil structures in case of unforeseen accidents. However, currently, most analytical research is carried out under the assumption of material elasticity for problem simplification, leading to the deviation of analysis results from actual situations. On this account, a progressive collapse analysis procedure for truss structures is proposed, based on the assumption of elastoplastic materials. A plastic importance coefficient was defined to express the importance of truss members in the entire system. The plastic deformations of members were involved in the construction of local and global stiffness matrices. The conceptual removal of a member was adopted, and the impact of the member loss on the truss system was quantified by bearing capacity coefficients, which were subsequently used to calculate the plastic importance coefficients. The member failure occurred when its bearing capacity arrived at the ultimate value, instead of the elastic limit. The extra bearing capacity was embodied by additional virtual loads. The progressive collapse analysis was performed by iterations until the truss became a geometrically unstable system. After that, the critical progressive collapse path inside the truss system was found according to the failure sequence of the members. Lastly, the proposed method was verified against both analytical and experimental truss structures. The critical progressive collapse path of the experimental truss was found by the failure sequence of damaged members. The experimental observation agreed well with the corresponding analytical scenario, proving the method feasibility.

Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study.

OBJECTIVE: To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs) for monotherapy of adult patients with focal epilepsy in routine clinical practice. METHODS: Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), topiramate (TPM), or oxcarbazepine (OXC) as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD), were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure. RESULTS: This study included 654 patients: CBZ (n=125), VPA (n=151), LTG (n=135), TPM (n=76), and OXC (n=167). The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]); TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74]), and OXC was better than VPA (0.86 [0.78-0.96]). After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs. OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]). CONCLUSION: LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.

Idazoxan reduces blood-brain barrier damage during experimental autoimmune encephalomyelitis in mouse.

We have previously shown that Idazoxan (IDA), an imidazoline 2 receptor ligand, is neuroprotective against spinal cord injury caused by experimental autoimmune encephalomyelitis (EAE) in mouse, an animal modal of multiple sclerosis (MS). However, the protective mechanism remains unclear. Here, we provided evidence to show that IDA confers neuroprotection through reduction in blood-brain barrier (BBB) damage. EAE was induced by immunizing C57 BL/6 mice with myelin oligodendrocyte glycoprotein35-55 amino acid peptide (MOG35-55). IDA was administrated for 14 days after MOG immunization at 2 mg/kg (i.p., bid). Significant reduction in BBB damage occurred in the IDA-treated group of mice compared with the saline-treated group, as evidenced by the reduction in Evan׳s blue content in the brain tissue and the reduced BBB tight junction damage viewed under a transmission electron microscope. Moreover, EAE-induced reductions in tight junction proteins (JAM-1, Occludin, Claudin-5 and ZO-1) were also significantly ameliorated in IDA-treated mice, all of which supported the notion that IDA reduced BBB damage. Interestingly, the expression levels of extracellular matrix metalloproteinase-9 (MMP-9) and the ratio of MMP-9 against tissue inhibitor of metalloproteinase-1 (TIMP-1), which is known to be associated with MS-induced BBB damage, were significantly reduced in IDA-treated group, lending further support to the hypothesis that IDA confers brain protection through reducing BBB damage. This study raised a possibility that IDA is a promising pro-drug for development against MS.