Effect of second-generation antiepileptic drugs on diplopia: a meta-analysis of placebo-controlled studies / 华中科技大学学报（医学）（英德文版）

Different antiepileptic drugs (AEDs) may cause similar adverse effects, one of which is diplopia. However, the AEDs causing diplopia and the dose-response effect of each drug remains uncertain. In this study, we compared several second-generation AEDs to find out whether they would contribute to the risk of diplopia and their effect-causing dose. A meta-analysis was performed on 19 studies in agreement with our inclusion criteria. The results showed that eight commonly used second-generation AEDs (gabapentin, levetiracetam, oxcarbazepine, lamotrigine, pregabalin, topiramate, vigabatrin and zonisamide) could cause diplopia. The reported odds ratios (ORs) ranged from 1.406 to 7.996. Ranking risks from the highest to the lowest ORs of the eight AEDs of any dose resulted in the following order: use of oxcarbazepine (7.996), levetiracetam (7.472), lamotrigine (5.258), vigabatrin (3.562), pregabalin (3.048), topiramate (2.660), gabapentin (1.966), zonisamide (1.406). Taking into account the ORs above, we can conclude that second-generation AEDs of any dose may cause diplopia. However, the levetiracetam-caused diplopia needs to be further studied according to the data (OR, 7.472; 95% confidence interval, 0.375-148.772). These findings ask for better concerns about patients' quality of life when giving antiepileptic treatments.

Effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and progression of amygdala kindling / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to evaluate the effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and its roles in epileptogenesis. Electrodes were implanted into the right amygdala of male adult Wistar rats. Kindling was accomplished by using stimulus strength of 500 μA applied daily to the amygdala until 10 consecutive stage 5 seizues were induced. Then effect of ZM241385 was studied in fully kindled rats after intracerebroventricular administration of the drug. In addition, the effect on kindling progression was evaluated through ZM241385 injection before daily stimulation. In all experiments, behavioral changes in the rats in response to ZM241385 were monitored closely. The results showed that, in fully amygdala-kindled rats, ZM241385 (0.001-0.1 nmol/L) decreased afterdischage duration (ADD), motor seizure duration (MSD), stage 5 duration (S5D) and seizure duration (SD), but only the effect on ADD was dose-dependent. The doses of 0.001-0.1 nmol/L had no influence on stage 4 latency (S4L) and seizure stage (SS). The dosages of 0.0001 and 1 nmol/L of ZM241385 did not exert any effect on all seizure parameters. In contrast to the results in fully amygdala-kindled rats, ZM241385 (0.001-0.1 nmol/L) had minimal or no effects on the progression of amygdala-kindled seizures. We are led to the conclusion that although ZM241385 had no influence on the progression of amygdala-kindled seizures, it had potent anti-convulsant profile and little adverse effects at the dosage of 0.001-0.1 nmol/L, suggesting that the agent is effective against the amygdala-kindled seizures.

Effect of second-generation antiepileptic drugs on diplopia: A meta-analysis of placebo-controlled studies / 华中科技大学学报（医学）（英德文版）

Different antiepileptic drugs (AEDs) may cause similar adverse effects, one of which is diplopia. However, the AEDs causing diplopia and the dose-response effect of each drug remains uncertain. In this study, we compared several second-generation AEDs to find out whether they would contribute to the risk of diplopia and their effect-causing dose. A meta-analysis was performed on 19 studies in agreement with our inclusion criteria. The results showed that eight commonly used second-generation AEDs (gabapentin, levetiracetam, oxcarbazepine, lamotrigine, pregabalin, topiramate, vigabatrin and zonisamide) could cause diplopia. The reported odds ratios (ORs) ranged from 1.406 to 7.996. Ranking risks from the highest to the lowest ORs of the eight AEDs of any dose resulted in the following order: use of oxcarbazepine (7.996), levetiracetam (7.472), lamotrigine (5.258), vigabatrin (3.562), pregabalin (3.048), topiramate (2.660), gabapentin (1.966), zonisamide (1.406). Taking into account the ORs above, we can conclude that second-generation AEDs of any dose may cause diplopia. However, the levetiracetam-caused diplopia needs to be further studied according to the data (OR, 7.472; 95% confidence interval, 0.375-148.772). These findings ask for better concerns about patients' quality of life when giving antiepileptic treatments.

The dynamic changes of adenosine receptors imbalance during kindling by lithium chloride-pilocarpine / 中华神经科杂志

Objective To investigate the dynamic changes of adenosine receptors, A1 (A1R) and A2a (A2aR) in the brain from the acute to chronic phase after kindling and to explore the correlation between seizure and expression level of A1R and A2aR. MethodsRats were randomly selected into the testing model, reference and normal control groups.Testing rats were kindled by lithium choride-pilocarpine, reference rats were treated with saline, and no treatment was given in normal control group. The dynamic expression of A1R and A2aR were detected by RT-PCR, immunofluorescence staining and Western blot at time-points of 24 hours, 1 month and 6 months post-kindling. Results In the acute phase of 24 hours after kindling, the A1R expression level (mRNA level was (1. 1483 ±0. 1182); Western blot result was ( 0. 7872± 0. 0621 ) ; immunofluorescence staining count was ( 76. 17 ± 4. 62 )/HP) was increased and A2aR (mRNA level was (0. 8338±0. 0572) ; Western blot result was (0. 2098 ±0. 0257) ; immunofluorescence staining count was (43. 83 ± 5. 12 )/HP) was decreased.The results showed statistically difference compared with the reference and normal groups (P< 0. 05 ). In the later chronic phase of 1 month and 6 months after kindling, the expression level of A1R was decreased and A2aR was increased. These data revealed statistically significant difference (P <0. 01 ). Furthermore, the comparison of the results in 1 month and 6 months after kindling found that the expression of AIR was lower in 6 months (mRNA level was (0. 5682 ±0. 0443) ; Western blot result was (0. 7749 ±0. 0262) ; immunofluorescence staining count was (38. 50 ±4. 81 )/HP) than in 1 month and that of A2aR was higher in 6 months (mRNA level was (1. 2169±0. 0332) ; Western blot result was (0. 7080 ±0. 0371 ); immunofluorescence staining count was (114. 50 ± 4. 04)/HP). The differences were statistical significant (t = - 19. 02--13.28, P < 0. 05). ConclusionsThe expressions of A1R and A2AR during and after kindling presents a bidirectional change. In the acute phas the expression of AR is regulated to suppress seizures. While in the chronic phase, the repeated seizures result in the change of A1R and A2aR expression in the opposite direction. This mechanism plays an important role in refractory seizures.

Characteristic distribution of stroke localization due to moyamoya disease and its mechanisms / 中华神经科杂志

Objective To clinically analyze the frequent stroke localizations of moyamoya disease in order to improve our cognition toward it and reduce missed diagnosis. Methods All 32 patients were prospectively analyzed over the past 10 years in our hospital. Results The ratio of female to male was 1.28 and their age of onset ranged from 7 to 47 years old. Mean age of 5 ischemic stroke patients (15.6%) was 24 and mean age of 21 haemorrhagic stroke patients (65.6%) was 33 while mean age of 6 mixed type stroke patients (18. 8% ) was 32. The frequent ischemic stroke localizations were frontoparietal lobe (60%),temporo-occipital lobe (20%), and periventricular zone (20%). The frequent haemorrhagic stroke iocalizations were periventricular zone (42.8%), ventricle (39.2%), temporo-occipital lobe (10. 8%) and subarachnoid space (7.2%). No cerebellum and brain stem stroke occurred. Conclusion Adult patients usually develop intracranial hemorrhage. Moyamoya disease should be considered severely when adult patients develop periventricular and ventricular intracranial hemorrhage, frontoparietal cerebral infarction or adolescent patients develop ischemic stroke, especially companied with epilepsy.

Clinical characteristics of paroxysmal kinesigenic choreoathetosis: diagnosis, treatment and prognosis / 华中科技大学学报（医学）（英德文版）

The clinical characters, diagnosis and differential diagnosis of paroxysmal kinesigenic choreoathetosis (PKC), and efficacy of the anti-epileptic drugs (AEDs) were investigated. Thirty-one patients with PKC were collected, and the clinical characters and change of EEG were analyzed. The average age of the first attack was 16.8 years old and the pinnacle was 10 to 20 years old. There were definite causes for every attack and the sudden movement was the most common one (92%). Time for the whole attack was always less than 1 min. The attack presented with muscle tension disturbance (83.9%), movement like dancing (16.1%), abnormal movement of mouth and face and other symptoms (16.2%). The attack tended to be very frequent and 71% patients were beyond once per day. The EEG examination and image scan of primary PKC were normal in most patients. Low dosage of AEDs could control the attack of 50%-77.3% patients. It was concluded that PKC was a common disease of movement disorder. The therapy by AEDs was very effective. PKC should be differentiated from epilepsy and the relationship between PKC and epilepsy needs further research.

Biological characteristics and multi-directional differentiation of bone marrow mesenchymal stem cells in children / 中国组织工程研究

BACKGROUND: It has been reported that in China, human bone marrow mesenchymal stem ceils are mostly harvested from adults. Studies on bone marrow mesenchymal stem cells in children are few.OBJECTIVE: To isolate and expand bone marrow mesenchymal stem cells from children, and to analyze the biological characteristics of bone marrow mesenchymal stem cells and their potential of differentiating into osteoblasts, adipocytes and neural like cells.DESIGN: Observational comparative study.SETTING: Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: Experiments were performed at the Laboratory of Department of Orthopaedics of Wuhan Tongji Hospital from March to September 2006. Bone marrow mesenchymal stem cells were collected from one boy patient and two girl patients aged 5-8 years, who received pelvis osteotomy for dysplasia of the hip joint. The experimental procedures were approved by the Hospital Ethics Committee and family members of all children patients singed the informed consent.Dexamethasone, vitamin C, β-sodium glycerophosphate, 3-1sobutyl-1-methylxanthine, insulin, indometacin and butylated hydroxyanisole were bought from Sigma Company. Dimethyl sulphoxide was purchased from Amersco Company.METHODS: Bone marrow mesenchymal stem cells were cultured from mononuclear cells isolated over a Percoll gradient.Bone marrow mesenchymal stem cells were observed under an inverted phase contrast microscope. Bone marrow mesenchymal stem cells could differentiate into osteoblasts, adipocytes and neural like cells with osteoblast inductor (β-sodium glycerophosphate, dexamethasone, vitamin C), lipoblast inductor (dexamethasone, 3-isobutyl-1-methylxanthine,bovine insulin, indometacin) and serum-free medium inductor (dimethyl sulphoxide, butylated hydroxyanisole) respectively.Osteoblast marker (alkaline phosphatase, osteocalcin mRNA, calcium node), adipocyte marker (lipid droplet, PPAR γ-2mRNA) and neural ceil-like marker (nissl body, neuron specific enolase, neurofilament protein) were respectively determined by the immunohistochemical method, polymerase chain reaction and immunocytochemical method.MAIN OUTCOME MEASURES: ①Appearance and proliferation of bone marrow mesenchymal stem ceils from children,and ②determination results of osteoblast, adipocyte and neural cell markers.RESULTS: ①Children bone marrow mesenchymal stem cells could easily adhere to the wall, appeared fusiform, had high reproductive activity and arranged vortically after fusing. ②Appearance of bone marrow mesenchymal stem cells changed after receiving inductor. Osteoblast marker, adipocyte marker and neural cell-like marker were positive after chemical staining, polumerase chain reaction and immunocyte staining.CONCLUSION: Children bone marrow mesenchymai stem cells show stable proliferation, passage and multi-direction differentiation towards osteoblasts, adipocytes and neural like cells.

Proliferation of neural progenitor cells and evaluation of neurologic function in cerebral hemorrhagic rats after transplantation of olfactory ensheathing cells / 中国组织工程研究

BACKGROUND: Being a kind of regenerative and auto-transplanting cell, olfactory ensheathing cell (OEC) has been extensively concerned on transplantation treatment for spinal disease. Concerning to the transplantation in treatment of cerebral hemorrhage, it is expected a further accumulation of experimental results at present.OBJECTIVE: To observe the proliferation of neural progenitor cells in cerebral hemorrhagic rats after OEC transplantation and to evaluate the therapeutic effects of OEC transplantation on cerebral hemorrhage.DESIGN: Completely randomized controlled experiment.SETTING: Department of Neurology of Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.MATERIALS: The experiment was performed in Research Center for Clinical Neurology , Tongji Medical College of Huazhong University of Science and Technology from March 2002 to March 2003. Thirty-two healthy male Wistar rats were employed and randomized into 2 groups, 16 rats in each. In OEC transplantation group, on the 3rd day of modeling hemorrhage of caudate nucleus, OEC suspension 10 μL was injected evenly in the brain of rat (1 μL/min). In the control group, physiological saline 10 μL was injected.METHODES: Neural function evaluation was done before transplantation,on the 3rd, 7th, 14th and 30th days after transplantation successively. On the first day after modeling, 1 rat was collected from each of two groups to prepare brain tissue section. Myelin sheath blue staining was used for observation of neuronal axonal myelin sheath. Never fiber argentophil staining was used for observation of never fiber. One rat was collected from each of two groups on the 3rd, 7th, 14th and 30th days after transplantation successively to prepare paraffin section. The survival and migration after OEC transplantation as well as proliferation of neural progenitor cell were observed.The count of neural progenitor cell was recorded.myelin sheath and nerve fiber after cerebral hemorrhage in rats of two function deficits on the 3rd, 7th, 14th and 30th days after cerebral hemorrhage in rats of two groups.around and in hematoma on the 30th day after cerebral hemorrhage: In transplantation group, myelinated amount and nerve fiber amount were cell after cerebral hemorrhage in rats of two groups: on the 7th, 14th and 30th days after cerebral hemorrhage, the amount of neural progenitor cell in OEC transplantation group was more remarkably than that in the control group [(41.1 ±2.4)pcs/vision field, (34.5 ±1.2)pcs/vision field; (43.6±1.2)pcs/vision rield, (37.2±2.0)pcs/vision field; (19.3±1.0)pcs/vision rield, ( 14.2±0.4)pcs/videficits after cerebral hemorrhage in rats of two groups: In OEC transplantation group, on the 14th and 30th days, the evaluation was lower remarkably than the 3rd day [(2.21 ±0.20)scores, (1.50±0.21)scores, (2.74±0.21)scores, (t=2.06, 3.27, P ＜ 0.05)]. In the control group, that on the 30th day after cerebral hemorrhage was lower than that on the 3rd day [(1.96±0.12)scores ,(2.76±0.20) scores, (t=2.47, P ＜ 0.05 )].tion of intracerebral nerve cell, re-myelination and building-up synaptic system so as to recover the motor function and accelerate repair of injured tissue.