Outcomes of sustained-release formulation of valproate and topiramate monotherapy in patients with epilepsy: a multi-centre, cohort study.

BACKGROUND: New-generation antiepileptic drugs (AEDs) tend to replace traditional AEDs as the first-line choice for epilepsy. However, whether this change results in better outcome, especially in China, remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Two broad spectrum AEDs, the traditional drug of sustained-release formulation of valproate (SRVPA) and the new-generation drug of topiramate, were compared in patients with epilepsy as monotherapy in this multi-centre, observational cohort study from 2000 to 2011. The primary outcome was time to treatment failure. The secondary outcomes included time to first seizure, time to 12-month remission, and time to 24-month remission. Drug tolerability was assessed. Cox proportional hazard models (95% confidence interval [CI]) were used to analyse the relative risks expressed as hazard ratios (HR). Of the 1008 recruited patients, 519 received SRVPA and 489 received topiramate. SRVPA was better than topiramate (28.3% vs. 41.5%; HR = 0.62, [95% CI 0.49-0.77]; p<0.0001) in primary outcome, and in time to first seizure (56.1% vs. 69.3%; HR = 0.73, [95% CI 0.62-0.86]; p = 0.0002). No significant difference was observed between two groups in time to 12-month remission (52.6% vs. 42.5%; HR = 1.01, [95% CI 0.84-1.23]; p = 0.88) and time to 24-month remission (34.7% vs. 25.2%; HR = 1.11, [95% CI 0.88-1.42]; p = 0.38). 36 patients (6.9%) in SRVPA group and 37 patients (7.6%) in topiramate group presented treatment failure associated with intolerable adverse events, there was no significant difference between the two groups (p = 0.70). CONCLUSIONS: The SRVPA is more suitable than topiramate for Chinese epileptic patients, and our results support the viewpoint that traditional AEDs should be the first-line choice for epilepsy rather than new-generation AEDs.

Long-term retention rate of topiramate as initial monotherapy in Chinese patients with newly diagnosed epilepsy: a prospective, observational study.

This is a large-sample, prospective, long-term observational study to assess the retention rate of topiramate as initial monotherapy in Chinese patients with newly diagnosed epilepsy. The retention rate was calculated by Kaplan-Meier method using intention-to-treatment analysis. Cox proportional hazard models were used to analyze the risk factors for retention rate. A total of 229 patients were enrolled into this study. The retention rate was 75.5% at 1 year, 47% at 6 years. Three risk factors for treatment failure were female gender, rural residence, and frequent seizures before treatment. Four predominant causes leading to treatment failure were: lack of efficacy (7.4%), adverse effects (10.9%), follow-up loss (15.7%), and subjective misunderstanding (8.3%). Adverse effects occurred in 129 (56.3%) patients, with 7 (3.1%) patients suffered from renal calculus. This study suggests the long-term retention rate of topiramate as initial monotherapy is high in Chinese patients. Lower initial dose, lower target dose and slower titration contribute to better tolerability. Frequent abdominal ultrasound for detecting renal calculus is necessary. Rural patients and patients with poor education level should be paid more attention by physicians to ensure continued therapy.

Increased insulin receptor expression in anterior temporal neocortex of patients with intractable epilepsy.

The insulin receptor (IR) is a tyrosine kinase receptor that binds to insulin and plays pivotal roles in energy homeostasis, neuronal growth, neuronal survival, synaptic plasticity and cognitive function. The biological mechanisms of intractable epilepsy involve energy metabolism, neuron loss, neurogenesis and abnormal neural networks. Here, we evaluated the expression of the IR in the anterior temporal neocortex of patients with intractable epilepsy (IE) by immunohistochemistry, double-label immunofluorescence and immunoblotting. We compared these tissues against histologically normal anterior temporal lobes from individuals treated for post-trauma intracranial hypertension. We found that the IR was coexpressed with neuron-specific enolase (NSE) and that IR expression increased in the anterior temporal neocortex of epileptic patients. On the basis of the potential physiological effects of IR, our findings suggest that increased expression of the IR is a consequence of epileptic seizures and a cause of IE.

Abnormal expression of netrin-G2 in temporal lobe epilepsy neurons in humans and a rat model.

The membrane-bound axon guidance molecule netrin-g2 is preferentially expressed in the central nervous system and plays a role in synapse formation and maintenance. Using immunohistochemistry, immunofluorescence, and Western blotting, we investigated the possible correlation between netrin-g2 expression and intractable epilepsy (IE) using surgical samples from epilepsy patients. We used 35 samples of temporal neocortex from patients undergoing surgery for drug-refractory epilepsy and 15 autopsy samples from individuals who died in traffic accidents (i.e., samples of normal human brain). We also examined netrin-g2 expression in the hippocampus and adjacent cortex of rats with temporal lobe epilepsy (lithium chloride-pilocarpine model). Netrin-g2 was expressed in the membrane and cytoplasm of neurons from control specimens, and expression was higher in tissue from patients with intractable epilepsy. Western blotting of rat brain tissue showed that netrin-g2 was upregulated starting at 6h after kindling. Maximal expression was seen around 2 days, and relatively high expression was maintained until 30 days. Expression then returned to normal levels at 60 days, which was consistent with the immunohistochemical and immunofluorescence results. These data implicate netrin-g2 in the pathophysiology of epilepsy and are consistent with the hypothesis that this protein may participate in the abnormal development of synapses and in neuron migration.

[Clinical and epidemiological features of the five kinds of new epileptic syndrome].

OBJECTIVE: To investigate the clinical and epidemiological feature of the five kinds of new epilectically syndrome. METHOD: A retrospective study was conducted, by computer inquiry and manual retrieval, on 5300 patients with complete history records who had been followed up regularly in the epilepsy center of the First Affiliated Hospital of Chongqing University in the past 20 years to discover the cases that could be diagnosed as with the five kinds of new epileptic syndromes. RESULTS: Survey was finished in 4894 of the 5300 patients. Two cases of familial temporal lobe epilepsy, one case of familial partial epilepsy with variable foci, fourteen cases with mesial temporal epilepsy, and five cases with startle-provoked epileptic were discovered. CONCLUSION: Patients with the five kinds of new epileptic syndrome have been discovered in China too. It is beneficial to study the clinical and epidemiological features of those new epileptic syndromes.