Treatment of epilepsy in adults: expert opinion in China.

OBJECTIVE: The goal of this study was to survey a group of epileptologists in China regarding the treatment of adult epilepsy. METHODS: A questionnaire on treatment of adult epilepsy was sent to a group of opinion leaders in the field of epilepsy. RESULTS: For initial monotherapy for idiopathic generalized epilepsy (IGE), valproate was rated as the treatment of choice. In symptomatic localization-related epilepsy (SLRE)/simple partial seizures and SLRE/complex partial seizures, carbamazepine and oxcarbazepine were the respective treatments of choice, whereas in SLRE/secondarily generalized tonic-clonic seizures, carbamazepine, lamotrigine, and oxcarbazepine were treatments of choice. For women who were pregnant or trying to conceive, lamotrigine was the treatment of choice for both IGE and SLRE. In people with epilepsy who were HBsAg positive, whether liver function was normal or not, topiramate and levetiracetam were treatments of choice for IGE. Valproate and levetiracetam were treatments of choice for seizures in the emergency department. CONCLUSION: A high level of consensus was reached on most treatments of choice and first-line treatments for patients with epilepsy, which were in accordance with published US expert opinion.

eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells.

OBJECTIVE: We investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K)/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs). METHODS: Cortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR. RESULTS: Mdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs. CONCLUSIONS: eEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.

Enhanced brain delivery of lamotrigine with Pluronic(®) P123-based nanocarrier.

BACKGROUND: P-glycoprotein (P-gp) mediated drug efflux across the blood-brain barrier (BBB) is an important mechanism underlying poor brain penetration of certain antiepileptic drugs (AEDs). Nanomaterials, as drug carriers, can overcome P-gp activity and improve the targeted delivery of AEDs. However, their applications in the delivery of AEDs have not been adequately investigated. The objective of this study was to develop a nano-scale delivery system to improve the solubility and brain penetration of the antiepileptic drug lamotrigine (LTG). METHODS: LTG-loaded Pluronic(®) P123 (P123) polymeric micelles (P123/LTG) were prepared by thin-film hydration, and brain penetration capability of the nanocarrier was evaluated. RESULTS: The mean encapsulating efficiency for the optimized formulation was 98.07%; drug-loading was 5.63%, and particle size was 18.73 nm. The solubility of LTG in P123/LTG can increase to 2.17 mg/mL, making it available as a solution. The in vitro release of LTG from P123LTG presented a sustained-release property. Compared with free LTG, the LTG-incorporated micelles accumulated more in the brain at 0.5, 1, and 4 hours after intravenous administration in rats. Pretreatment with systemic verapamil increased the rapid brain penetration of free LTG but not P123/LTG. Incorporating another P-gp substrate (Rhodamine 123) into P123 micelles also showed higher efficiency in penetrating the BBB in vitro and in vivo. CONCLUSION: These results indicated that P123 micelles have the potential to overcome the activity of P-gp expressed on the BBB and therefore show potential for the targeted delivery of AEDs. Future studies are necessary to further evaluate the appropriateness of the nanocarrier to enhance the efficacy of AEDs.

Tenidap is neuroprotective in a pilocarpine rat model of temporal lobe epilepsy.

BACKGROUND: Tenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 (COX-2) and cytokines in vitro. This study aimed to evaluate the neuroprotective effect of tenidap in a pilocarpine rat model of temporal lobe epilepsy (TLE). METHODS: Tenidap was administered daily at 10 mg/kg for 10 days following pilocarpine-induced status epilepticus (SE) in male Wistar rats after which prolonged generalized seizures resulted in TLE. After tenidap treatment, spontaneous recurrent seizures (SRSs) were recorded by video monitoring (for 7 hours per day for 14 days). The frequency and severity of the SRSs were observed. Histological and immunocytochemical analyses were used to evaluate the neuroprotective effect of tenidap and detect COX-2 expression, which may be associated with neuronal death. RESULTS: There were 46.88 ± 10.70 survival neurons in tenidap-SE group, while there were 27.60 ± 5.18 survival neurons in saline-SE group at -2.4 mm field in the CA3 area. There were 37.75 ± 8.78 survival neurons in tenidap-SE group, while there were 33.40 ± 8.14 survival neurons in saline-SE group at -2.4 mm field in the CA1 area. Tenidap treatment significantly reduced neuronal damage in the CA3 area (P < 0.05) and slightly reduced damage in the CA1 area. Tenidap markedly inhibited COX-2 expression in the hippocampus, especially in the CA3 area. CONCLUSION: Tenidap conferred neuroprotection to the CA3 area in a pilocarpine-induced rat model of TLE by inhibiting COX-2 expression.

Evaluation of clinical aspects and quality of life as risk factors for depression in patients with epilepsy.

The purpose of this study was to investigate clinical aspects and quality of life (QOL) as risk factors for depression in patients with epilepsy. One hundred and forty outpatients with a diagnosis of epilepsy who were attending our epilepsy center participated. Patients anonymously filled out a questionnaire with clinical data related to epilepsy. Depression level was evaluated by the Hamilton Depression Rating Scale-17 (HAMD-17), and quality of life was evaluated by the Quality of Life in Epilepsy-31 (QOLIE-31). Thirty-six patients with epilepsy suffered from depression (25.7%). Complex partial seizures (OR=0.112) and number of seizure types (OR=3.773) were found to be clinical risk factors for depression. Low scores for seizure worry (OR=0.947) and social function (OR=0.947) on the QOLIE-31 increased the probability of depression in patients with epilepsy.

[Clinically anatomic study on the relation between the form of pleural cupula and its surrounding commonly-used acupoints].

OBJECTIVE: To explore the relation of the form of pleural cupula of the normal adult with safety of acupuncture at commonly-used acupoints around the pleural cupula. METHODS: The safe depth for the commonly-used acupoints around the pleural cupula and the relation with the form of pleural cupula were investigated in 46 adult corpses with small Kirschner wire location and arrangement dissection. RESULTS: The width of the pleural cupula projection equal to clavicle medial 1/3 accounted for 32. 6% of all the corpses, and the width of the pleural cupula projection more than clavicle medial 1/3 accounted for 59. 8% of all the corpses, the width of the pleural cupula projection less than clavicle medial 1/3 and pleural cupula medial margin located at the sternoclavicular joint medial accounted for 7.6% of all the corpses. The observed points such as Tiantu (CV 22), Qishe (ST 11), Jianjing (GB 21), Dingchuan (EX-B1), Dazhu (BL 11) which were considered be not related to the pleural cupula. When acupuncture is carried out according to criteria of acupoint location and needling direction, and the needle exceeded a limit, the pleural menbrane will be broken and induce destruction. CONCLUSION: Position and form of the pleural cupula have anatomical relation to acupuncture accident for needling the points around the superior pleural cupula, which should be played attention to.