BACKGROUNDIt is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy.

METHODSThis is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated.

RESULTSA total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%).

CONCLUSIONThis study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure, 12-month remission rate, and retention rate.

Adolescent ; Adult ; Anticonvulsants ; therapeutic use ; Carbamazepine ; analogs & derivatives ; therapeutic use ; China ; Epilepsies, Partial ; drug therapy ; Female ; Fructose ; analogs & derivatives ; therapeutic use ; Humans ; Male ; Middle Aged ; Piracetam ; analogs & derivatives ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Triazines ; therapeutic use ; Valproic Acid ; therapeutic use ; Young Adult

OBJECTIVETo study topiramate's new functions according to the medicinal property combinations, in order to apply the traditional Chinese medicinal theory in discovering new purposes of old drugs.

METHODAccording to New Traditional Chinese Medicinal Families--Chemical Traditional Chinese Medicines, the authors found out topiramate's property. Then based on the therapeutic principle of diabetes, hypertension, epilepsy and lung cancer, as well as the relations of efficacies and medicinal property combinations, they summarized the corresponding medicinal property combination modes, compared topiramate's medicinal property combination mode with corresponding medicinal property combination modes of these diseases, and predict topiramate's new functions.

RESULTAccording to the comparison, the corresponding medicinal property combinations were consistent with topiramate's medicinal property combinations as evidenced by corresponding literatures, whereas other medicinal property combinations were not.

CONCLUSIONBased on medicinal property combination modes, the authors screened topiramate's new functions according to e of TCM clinical experience, discovered topiramate's therapeutic effects on diabetes, hypertension and lung cancer in addition to epilepsy, and explore new drug function according to medicinal property combination modes, which could help greatly shorten the new drug R&D period.

Diabetes Mellitus ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Fructose ; analogs & derivatives ; chemistry ; therapeutic use ; Humans ; Hypertension ; drug therapy ; Lung Neoplasms ; drug therapy ; Phytotherapy

Child ; Epilepsy ; drug therapy ; Fructose ; adverse effects ; analogs & derivatives ; Glaucoma ; chemically induced ; Humans ; Male ; Sturge-Weber Syndrome ; complications

BACKGROUNDRecently, new anti-epileptic drugs (AEDs) have been more frequently selected to treat epilepsy. In the present study, we evaluated the dynamic changes of efficacy and safety of three newer AEDs for treating partial epilepsy in China.

METHODSPatients were collected sequentially and were divided into three groups which accepted oxcarbazepine (OXC), lamotrigine (LTG) or topiramate (TPM) therapy. Each group included monotherapy and add-on therapy subgroups. We followed all patients for one year and recorded the indexes of efficacy and safety in detail.

RESULTSA total of 909 patients finished the follow-up observation. No significant difference was found in proportion of patients with > or = 50% reduction, > or = 75% reduction and 100% seizure reduction in the LTG and OXC groups between the first and the second six months. In the TPM group there was a statistical difference between the first and the second six months in proportion of patients with > or = 50% reduction (P = 0.002), > or = 75% reduction (P < 0.0001) and 100% seizure reduction (P = 0.009) in the monotherapy subgroup, and about > or = 75% reduction and 100% seizure reduction in the add-on therapy subgroup (P < 0.0001). The efficacy between the add-on and monotherapy subgroups showed a statistical difference. The safety of the three newer AEDs was good.

CONCLUSIONSThe three newer AEDs all showed good efficacy and tolerability for partial epilepsy. And the efficacy can be maintained for at least one year.

Anticonvulsants ; therapeutic use ; Carbamazepine ; analogs & derivatives ; therapeutic use ; China ; Epilepsies, Partial ; drug therapy ; Follow-Up Studies ; Fructose ; analogs & derivatives ; therapeutic use ; Humans ; Treatment Outcome ; Triazines ; therapeutic use

OBJECTIVETo assess bone health in epileptic children who have been treated with topiramate (TPM) or carbamazepine (CBZ).

METHODSSixty-three epileptic children who received TPM or CBZ treatment and 36 eileptic children who did not receive any drug treatment (control group) were enrolled. Bone mineral density (BMD) at lumbar vertebrae (L1-L4) and radius-ulna was evaluated by the dual-energy X-ray absorptiometry method. Biochemical indices of bone metabolism, including serum calcium, phosphorus and alkaline phosphatase contents were measured.

RESULTSThe serum calcium content was higher in the TPM group (2.41+/-0.17 mmol/L), but it was lower in the CBZ group (2.15+/-0.26 mmol/L) than that (2.26+/-0.11 mmol/L) in the control group (p<0.05). The serum phosphorus content in both the TPM (1.55+/-0.17 mmol/L) and the CBZ groups (1.52+/-0.26 mmol/L) was significantly lower than that in the control group (1.70+/-0.30 mmol/L) (p<0.05). There were no significant differences in the serum content of alkaline phosphatase between three groups. BMD was significantly reduced in both the TPM and the CBZ groups when compared to the control group (p<0.05).

CONCLUSIONSTPM and CBZ may result in alterations in serum contents of calcium, phosphorus and alkaline phosphatase as well as BMD reduction.

Adolescent ; Alkaline Phosphatase ; blood ; Anticonvulsants ; adverse effects ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; metabolism ; Calcium ; blood ; Carbamazepine ; adverse effects ; Child ; Child, Preschool ; Epilepsy ; drug therapy ; metabolism ; Female ; Fructose ; adverse effects ; analogs & derivatives ; Humans ; Male ; Phosphorus ; blood

This is a long-term, open label, observational study aimed to broaden our clinical experiences in managing infants and toddlers with epilepsy. The long-term retention rate and side effects of topiramate (TPM) in them were evaluated and compared with carbamazepine (CBZ). A total of 146 children were involved in the study (TPM=41, CBZ=105). The retention rates at 24 , 36, and 48 months were 46.3%, 34.1%, 26.8% for TPM and 36.2%, 23.8%, 13.3% for CBZ, respectively. At 6 months after starting antiepileptic drugs (AED), the seizure freedom or clinical efficacy (seizure reduction rate more than 50 percent) were 73.2% for TPM and 62.9% for CBZ. The major side effects led to discontinuation included psychomotor slowing, poor oral intake from TPM and sleepiness and skin rash from CBZ. TPM was discontinued due to side effects in one case (2.4%) and lack of efficacy in five cases (12.2%), whereas CBZ was discontinued due to lack of efficacy (22.9%) and side effects (6.7%). As compared with CBZ, TPM showed the same long-term retention rate in children under the age of 2 yr, and no serious side effects. It is therefore concluded that TPM can be considered as a major AED for treating children with epilepsy under the age of 2 yr.
Anticonvulsants/adverse effects/*therapeutic use ; Carbamazepine/adverse effects/therapeutic use ; Child ; Child, Preschool ; Epilepsy/*drug therapy ; Female ; Follow-Up Studies ; Fructose/adverse effects/*analogs & derivatives/therapeutic use ; Humans ; Infant ; Male ; Treatment Outcome

Accidents ; Benzodiazepines ; administration & dosage ; Brain Injuries ; therapy ; Craniocerebral Trauma ; therapy ; Electroconvulsive Therapy ; methods ; Fructose ; administration & dosage ; analogs & derivatives ; Humans ; Male ; Memantine ; administration & dosage ; Middle Aged ; Pilot Projects ; Pyridines ; administration & dosage ; Valproic Acid ; administration & dosage

OBJECTIVEThe event related potential (ERP-P300) is useful to determine cognitive disturbances. This study examined the changes of ERP-P300 following different dosages of topiramate (TPM) treatment in children with epilepsy in order to investigate the effect of different dosages of TPM on cognitive function.

METHODSThirty cases of benign childhood epilepsy with centrotemporal spikes (BECTS) were first administered with TPM at a dosage of 2 mg/kg/d for 6 months. Afterwards they received another 6 months of TPM treatment at a dosage of 5 mg/kg/d. ERP-P300 was tested before and after different dosages of TPM treatment.

RESULTSThere were no significant differences in the latency and amplitude of ERP-P300 before and after 6 months low dosages of TPM treatment. However, the latency was more prolonged and the amplitude was reduced in the ERP-P300 testing after 6 months high dosage of TMP treatment (P<0.01).

CONCLUSIONSThe effect of TPM on cognitive function is related to its dosage in children with epilepsy.

Adolescent ; Anticonvulsants ; therapeutic use ; Child ; Cognition ; drug effects ; Epilepsy ; drug therapy ; physiopathology ; psychology ; Event-Related Potentials, P300 ; drug effects ; Female ; Fructose ; analogs & derivatives ; therapeutic use ; Humans ; Male ; Reaction Time ; drug effects

OBJECTIVEThe pathogenesis of Tourette syndrome (TS) is associated with the disorders of neurotransmitters, such as dopamine (DA) and excitatory amino acids (EAA). Antiepileptic drugs such as topiramate have shown some effects on TS, but the mechanism has not been clearly identified. The objective of the research was to evaluate the relationship between the pathogenesis of TS and abnormality of neurotransmitters by determining the levels of brain free DA and plasma EAA in iminodipropionitrile (IDPN) induced head twitch response (HTR) rats, and to investigate the effects of topiramate on HTR induced by IDPN.

METHODSForty-eight Sprague-Dawley rats were randomly divided into six groups: blank control, TS model, and haloperidol-(0.5 mg/kg) and topiramate-treated (5, 10 and 20 mg/kg). HTR was induced by 7-day peritoneal injections of IDPN (150 mg/kg daily) and was used as TS model. Brain free DA levels and plasma levels of EAA were measured using ELISA and high performance liquid chromatography respectively 35 days after haloperidol or topiramate administration.

RESULTSBrain free DA levels were significantly lower and plasma EAA levels were significantly higher in the TS model group compared with those in the blank control group (P<0.05). Topiramate of 10 and 20 mg/kg significantly decreased the frequency of IDPN-induced HTR and significantly increased the level of brain free DA when compared with the TS model group (P<0.05). Topiramate of 20 mg/kg treatment as haloperidol treatment significantly decreased plasma EAA levels compared with the TS model group (P<0.05).

CONCLUSIONSThe pathogenesis of TS is related to the super-sensitivity of DA receptor in the center nervous system and the over-effect of plasma EAA. Topiramate can reduce IDPN-induced HTR, probably through the inhibition of DA and DA-receptor combination in the brain and the secretion and release of plasma EEA.

Animals ; Anticonvulsants ; therapeutic use ; Behavior, Animal ; drug effects ; Brain Chemistry ; drug effects ; Dopamine ; analysis ; Excitatory Amino Acids ; blood ; Fructose ; analogs & derivatives ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Tourette Syndrome ; drug therapy

OBJECTIVETo study the neuroprotective effects of topiramate (TPM) alone or together with folic acid (FA) on young rats with kindling-induced epilepsy.

METHODSRat models of epilepsy were prepared by pentylenetetrazol (PTZ)-induced kindling. Seventy-two 3-week-old male Wistar rats were randomly divided into 6 groups: four TPM-treated epilepsy groups (TPM 20, 40 or 80 mg/kg/d and TPM 40 mg/kg/d + FA 5 mg/kg/d), a positive control group (untreated epilepsy group) and a negative control group (normal control group). After two months of administration, behaviors of the rats were recorded; serum levels of neuron-specific enolase (NSE) were measured using ELISA; pathological changes in the hippocampus were observed.

RESULTSThe frequency of convulsion seizures in the 20, 40 and 80 mg TPM treatment and TPM+FA groups was 44.7 +/- 2.9, 44.3 +/- 3.1, 42.7 +/- 3.2, and 40.8 +/- 3.7 respectively, which were significantly lower than that in the positive control group (48.4 +/- 3.7) (P <0.01). Twenty, forty and eighty mg TPM treatment and TPM+FA treatment significantly reduced NSE levels from 35.71 +/- 5.97 microg/L of the control group to 27.40+/- 6.40, 24.79 +/- 6.22, 21.47 +/- 6.87 and 22.55 +/- 7.02 microg/L respectively (P <0.05). Neuronal apoptosis in the CA3 and CA1 regions were alleviated in the four TPM treatment groups compared with positive control. The number of necrotic neurons was progressively reduced with the increased dose of TPM. The 40 mg TPM+FA treatment group showed less necrotic neurons in the CA3 and CA1 regions than the 40 mg TPM alone treatment group.

CONCLUSIONSTPM has protective effects against epilepsy-induced neuronal damage. The effect is dose-dependent. A combination of TPM and FA can produce a synergistic effect.

Animals ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Epilepsy ; drug therapy ; pathology ; Folic Acid ; pharmacology ; Fructose ; analogs & derivatives ; pharmacology ; Hippocampus ; pathology ; Kindling, Neurologic ; drug effects ; Male ; Neuroprotective Agents ; pharmacology ; Phosphopyruvate Hydratase ; blood ; Rats ; Rats, Wistar