Objective To assess the effectiveness and safety of flunarizine for refractory epilepsy. Methods Relevant randomized controlled trials (RCTs) were searched from the database of PubMed, EMbase, Cochrane Library, CNKI, CBM, and VIP, and the related references were traced to obtain the information. The methodological quality of included RCTs was assessed using Jadad scale and meta-analysis was performed using RevMan 5.0 software. Results A total of eight studies involving 545 patients were included. The results of meta-analyses showed that: based on the conventional therapy, compared with placebo and none-treatment, flunarizine was more effective on adults and children with refractory epilepsy (OR=2.98, 95%CI 1.88 to -4.73; OR=33.75, 95%CI 4.13 to -276.00). Major adverse events of flunarizine were fatigue, dizziness, headache, and weight gain etc. All those symptoms except for the weight gain were observed in the early stage of medication, which might get self-cured or could disappear by constant medication or reducing the dose or symptomatic treatment. Conclusion The present study shows that based on the conventional therapy, flunarizine is effective and safe for refractory epilepsy.
Objective To assess the effectiveness and safety of progabide (PGB) for refractory epilepsy. Methods Randomized controlled trials (RCTs) on PGB treating refractory epilepsy were searched from the following databases as PubMed, EMbase, The Cochrane Library, CNKI, CBM and VIP from the date of their establishment to July 2011. The data of RCTs meeting the inclusive criteria were extracted according to Cochrane methods by two reviewers independently, and after the quality was evaluated and cross-checked, meta-analyses were conducted using RevMan 5.1 software. Results A total of seven studies involving 231 patients were included. The results of Meta-analyses showed that based on the conventional therapy, PGB was ineffective in treating refractory partial epilepsy compared with the placebo (OR=1.76, 95%CI 0.40 to 7.65, P=0.45), but it was superior to the placebo in treating refractory partial and generalized epilepsy (OR=4.46, 95%CI 2.06 to 9.65, P=0.000 1). The main adverse events of PGB were somnolence, dizziness and headache, which were mild and transient, which could turn to normal after reducing the dose of PGB and only a few patients needed to stop taking PGB. Conclusion Current studies shows that progabide may be effective in treating refractory partial and generalized epilepsy, but its effectiveness in treating refractory partial epilepsy is still unknown. The side effects of PGB are mostly mild. For the possibility of moderate selection bias existing in the quality of the included studies which may affect the authenticity of outcomes, so this conclusion still needs to be further proved by conducting more high-quality, large-scale and double-blinded RCTs.
ObjectiveTo understand the relationship between the anatomy and the function of the insula lobe cortex based on the stereo-electro encephalography (SEEG) by direct electric stimulation of the insula cortex performed in the patients who suffered from the refractory epilepsy. MethodsRetrospective review was performed on 12 individuals with refractory epilepsy who were diagnosed in the Department of Functional neurosurgery of RenJi Hospital from December 2013 to September 2015. We studied all the SEEG electrodes implanted in the brain with contacts in the insula cortex. Direct electric stimulation was given to gain the brain mapping of the insula. Results12 consecutive patients with refractory epilepsy were implanted SEEG electrodes into the insula cortex. In all, 176 contacts were in the insula cortex, and 154 were included. The main clinical manifestations obtained by the stimulation were somatosensory abnormalities, laryngeal constriction, dyspnea, nausea, flustered. While somatosensory symptoms were located in the posterior insula, visceral sensory symptoms distribute relatively in the anterior insula, and other symptoms were mainly in the central and anterior part. ConclusionsThe symptoms of the insula present mainly according to the anatomy, but some of them are mixed. In addition, the manifestations of the insula are usually complex and individually.
ObjectiveTo investigate the association between mTOR pathway and pharmacoresistance of Sprague-Dawley rat epilepsy model kindled by coriaria lactone. MethodsA kindling model of pharmacoresistant temporal lobe epilepsy was developed by injecting Sprague-Dawley (SD) rats with coriaria lactone (CL) (1.75 mg/kg, every 84 h). Normal SD rats were injected with normal sodium (NS) served as control group. Rats with five or more consecutive stage 5 seizures were included in kindled group. Immunohistochemistry was used to detect the levels of P-S6 in both groups. ResultsThe expressions of P-S6 in CA1 and CA3 were significantly higher compared with control group, and were mainly in astrocytes (P < 0.001). In addition, the expression of P-S6 in DG area was significantly higher than that in control group, with more granular cell and neuron (P < 0.001). ConclusionsThe mTOR pathway may be correlated with the drug resistance of refractory lobe epilepsy kindled by coriaria lactone.
Objectives To investigate the changes of serum monoamine neurotransmitters and myocardial enzymes in patients with refractory epilepsy (RE), and the possible effects on the cardiovascular system, which would contribute to provide help and guidance to the early warming and prevention to the sudden unexpected death in epilepsy (SUDEP). Methods We collected sixty patients with RE who admitted to Neurological department of First Hospital of Jilin University from December 2015 to December 2016. According to the exclusion criteria, we selected thirty-two patients into the study. The study included 21 males and 11 females patients. Epinephrine (EPI), norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), creatine kinase isoenzyme (CKMB), lactate dehydrogenase (LDH) and hydroxybutyrate dehydrogenase (HBDH) were measured in peri-ictal period and the interictal period in the patients. All the data were analyzed by SPSS17.0 statistical software. Results ① Thirty two patients were eligiblefor this study and the maleto female ratio is 21:11; The age ranged from 15 to 85 years old, with the average age of 50.9±17.6 years old. Twelve (37.5%) were older than 60 years old and 20 (62.5%) were under 60 years old. The epilepsy history ranged from 1 year to 14 years, with an average of 3.75±3.12 years; ② Comparing the levels of monoamine neurotransmitters in peri-ictal period and the interictal period in the patients with RE, we found that the level of EPI and LDH was significantly lower than that in interictal period, while the levels of NE and DA were significantly increased; ③ The results showed that EPI, NE and DA levels in patients under 60 were higher than over 60; ④ Patients were divided into four groups according to the etiology of the disease: idiopathic epilepsy group (10 cases, 31.25%), post-encephalitic epilepsy group (7 cases, 21.88%), post-stroke epilepsy group (9 cases, 28.12%) and epilepsy after brain injury group (6 cases, 18.75%). The results showed that the levels of EPI, NE and DA in the post-strokeepilepsy group were significantly lower than those in the other three groups. The level of CKMB in the idiopathic epilepsy group was higher than that in post-stroke epilepsy and epilepsy induced by brain injury patients. Conclusions RE patients have a higher level of serum NE and DA interictal period, suggesting that seizures may increase sympathetic nervous excitability. The patients under 60 years-old with RE release more catecholamines than young patients, suggesting that the latterwith intractable epilepsy may have higher sympathetic nerve excitability. And it may be associated with the higher incidence of SUDEP in young patients. Post-stroke epilepsyrelease less catecholamine than others, suggesting that the sympathetic nervous excitability is relatively low, and it may have relatively little damage to heart.
ObjectiveAnalyze and compare the differences in the efficacy and adverse reactions of various ketogenic diet (KD) in the treatment of refractory epilepsy in children.MethodsSystematic search of electronic databases, including PubMed, Embase, Ovid MEDLINE, Web of Science and the Central Register of Cochrane Controlled Trials, published in English January 2000 Relevant research from January to August 2020. Results: Finally, 11 articles were included and 781 cases were included. Meta-analysis (NMA) method was used to compare 6 classic ketogenic diets (Classic ketogenic diet, CKD), Gradual ketogenic diet initiation (GRAD-KD), and the first modified Atkins diet of 20 g carbohydrates/d (Initial 20 g of carbohydrate/day of modified Atkins diet, IMAD), modified Atkins diet (MAD), low glycemic index diet (LGID) and medium-chain fatty acid diet (Medium-chain triglyceride diet, MCT) Therapeutic effect and adverse reactions of 3, 6, and 12 months.ResultsFrom the results of the direct comparative analysis, CKD and MAD showed superior clinical efficacy in 50% seizure reduction at 3 months to CAU, and the difference was statistically significant [OR=10.58, 95%CI (3.47, 32.40), P<0.05; OR=11.31, 95%CI (5.04, 25.38), P<0.05]; the clinical efficacy of 90% seizure reduction at 3 months for MAD was superior to that of CAU with statistical significance [OR=4.95, 95%CI (1.90, 12.88), P<0.05]. The results of further network meta-analysis suggested that for the comparison of 50% seizure reduction at 3 months, IMAD, GRAD-KD, CKD, MAD, and MCT were superior to CAU, and the difference was statistically significant [OR=0.03; 95%CI (0.00, 0.30), P<0.05; OR=0.07; 95%CI (0.01, 0.76), P<0.05; OR=0.11; 95%CI (0.03, 0.35), P<0.05; OR=0.11; 95%CI (0.04, 0.35), P<0.05; OR=0.13; 95%CI (0.03, 0.67), P<0.05; OR=0.11; 95%CI (0.03, 0.35), P<0.05; OR=0.11; 95%CI (0.04, 0.35), P<0.05]. For the comparison of 90% seizure reduction at 3 months, CKD, GRAD-CK, IMAD, MAD, and MCT were superior to CAU, and the differences were statistically significant [OR=0.05; 95%CI (0.00, 0.31), P<0.05; OR=0.22; 95%CI (0.00, 0.39), P<0.05; OR=0.03; 95%CI (0.00, 0.62), P<0.05; OR=0.12; 95%CI (0.01, 0.60), P<0.05; OR=0.09; 95%CI (0.00, 0.91), P<0.05]. It is suggested in the cumulative probability plot that: the optimal clinical regimen for 50% seizure reduction at 3 months was IMAD (Rank1=0.91), the optimal clinical regimen for 50% seizure reduction at 6 months was CKD (Rank1=0.40), the optimal clinical regimen for 50% seizure reduction at 12 months was MCT (Rank1=0.64); the optimal clinical regimen for 90% seizure reduction at 3 months was IMAD (Rank1=0.94), the optimal clinical regimen for 90% seizure reduction at 6 months was LGIT (Rank1=0.44), and the optimal clinical regimen for 90% seizure reduction at 12 months was MCT (Rank1=0.41); the optimal clinical regimen for seizure reduction at 3 months was GRAD-CK (Rank1=0.46), the optimal clinical regimen for seizure reduction at 6 months was LGIT (Rank1=0.58), and the optimal clinical regimen for seizure reduction at 12 months was CKD (Rank1=0.56). It is suggested in the benefit-risk assessment that among the three KDs (CKD, MAD, MCT) with better 50% and 90% seizure reduction at 3 months and 6 months, combining with the incidence of adverse reactions, CKD was the optimal treatment regimen (CF=0.47, CF=0.86); among the two KDs (CKD, MAD) with better seizure reduction at 3 months and 6 months, combining with the incidence of adverse reactions, CKD was the optimal treatment regimen (CF=0.45); among the two KDs (CKD, MCT) with better 50% and 90% seizure reduction at 12 months, combining with the incidence of adverse reactions, CKD was the optimal treatment regimen (CF=0.65).ConclusionsIn this study, IMAD showed the optimal clinical efficacy at 3 months and MCT at 12 months. With stable efficacy and low incidence of adverse reactions in 12 months, CKD was the optimal treatment regimen for children with refractory epilepsy after the comprehensive evaluation.
ObjectiveAccording to the diagnosis and treatment analysis of 5 children with Febrile infection-related epilepsy syndrome (FIRES) and literature review, to explore the therapeutic effect of Ketogenic diet (KD).MethodsA retrospective analysis of the clinical status of 5 children with KD treatment of FIRES admitted to the Department of Pediatric Neurology, West China Second Hospital of Sichuan University from August 2016 to September 2019, combined with literature data, summarized their disease characteristics, prognosis and KD treatment effects.ResultsThe 5 cases of FIRES children were (5.8±2.0) years old and had a male to female ratio of 2∶3. They were all induced by fever followed by a status epilepticus that was difficult to control with drugs. The interval between fever and first seizure was 4 to 7 days, and the prodromal symptoms were higher Respiratory tract infections, dizziness, vomiting, fatigue, listlessness, loss of appetite, etc., convulsions manifested as focal or focal secondary systemic or general seizures, EEG showed slowing background rhythm, changes in multifocal epileptic discharge, early course of disease The cranial imaging examination was basically normal. As the course of the disease progressed, changes in brain atrophy gradually appeared, and abnormal signal shadows were seen in the forehead, parietal, occipital lobe, and periventricular. A variety of anti-epileptic drugs, hormones, gamma globulin, plasma exchange and other treatments have poor therapeutic effects and severe cognitive impairment. The KD treatment started to take effect within 2 weeks, and the convulsions were reduced. One case was completely controlled, and the cognitive function basically returned to normal with only mild learning disabilities; the convulsions were reduced by more than 50% in 2 cases, leaving mild to moderate cognitive impairment, The other 2 cases had poor long-term treatment effects, left intractable seizures and severe mental retardation.ConclusionFIRES is a serious epileptic encephalopathy, most of which leave severe cognitive impairment and refractory seizures. Drug therapy and prognosis are poor. KD treatment is beneficial to control seizures in children with FIRES in the acute stage.
ObjectiveTo analyze the clinical efficacy and safety of rapamycin in the treatment of Tuberous sclerosis complex ( TSC ) complicated with refractory epilepsy, and to provide scientific basis for the clinical treatment of this disease.MethodsRetrospective analysis was performed on 22 children with TSC complicated with refractory epilepsy admitted to Henan People's Hospital from 2017 to 2019, including 11 males and 11 females who met the inclusion criteria, with an average age of (27.91±36.92) months. They were treated with antiepileptic drugs and rapamycin at the same time, and followed up for at least 1 year.To observe the change of seizure frequency before and after treatment with rapamycin.ResultsThe mean reduction rate of seizure frequency in children with tuberous sclerosis complicated with refractory epilepsy was 52.1% 6 months after the addition of rapamycin, and 51.2% 12 months after the addition of rapamycin. The number of seizure-free days could be maintained. The difference before and after the addition of rapamycin was statistically significant (P<0.05).ConclusionThe addition of rapamycin in the treatment of TSC complicated with refractory epilepsy can reduce the frequency of seizure and increase the number of days without seizure, and the adverse reactions are mild/moderate. Rapamycin has certain safety in children with regular follow-up.
ObjectiveIn order to evaluate the efficacy, safety and tolerability of adjunctive perampanel in children with refractory epilepsy. MethodsThis study collected medical records of 34 children with refractory epilepsy, who were admitted to Children’s Hospital of Soochow University from January 2020 to January 2021. By comparing the baseline status with the status at 4, 8, 12, 24, 36, and 48 weeks of follow-up, the efficacy and adverse reactions of perampanel were evaluated. ResultsThe mean age of the patients treated with perampanel was 8.1±4.1 years. The male-to-female ratio was 1: 1. After the addition of perampanel, the average responder rate at the 4th, 8th, 12th, 24th, 36th, 48th weeks were 37.5%, 46.7%, 50.0%, 47.4%, 53.8%, 42.9%. The adverse events were reported by 32.4%, and the retention rate was 88.2%. ConclusionsPerampanel has good efficacy, safety and tolerability in the treatment of refractory epilepsy. Moreover, personalized treatment and better baseline seizure control may increase the effectiveness and retention rate of perampanel.