OBJECTIVE:To evaluate the efficacy and safety of acupuncture in the treatment of epilepsy.

METHODS:We first collected research data about randomized control trials (RCTs) of acupuncture treatment of epilepsy from databases CNKI, CBM, VIP and Wanfang using key words"(acupuncture)","(epilepsy)"or"(epilepsy)"or"(epilepsy)", and from PubMed, Google Scholar, and Cochrane Library using key words"acupuncture""needling""prod""epilepsy""epilepsies"or"seizure disorder"or"simple seizure"from the date of database construction to May 5, 2017. Then, two researchers extracted the study outcomes and evaluated the evidence qualification of the research data independently using GRADE profile 3.6 software and analyzed the primary outcome indexes using RevMan 5.3 and STATA 14.0.

RESULTS:Eleven articles containing 827 cases were included in the Meta-analysis. We found that acupuncture or acupuncture in combination with other conventional drugs had a significantly better efficacy than conventional drugs in the treatment of epilepsy [=3.94, 95%CI (2.49, 6.24),=5.85,<0.000 01]. There was a statistical heterogeneity (=0.04, l=60%), and the Meta-analysis was not feasible for the studies of acupuncture vs medication. Combination of acupuncture and Chinese traditional drugs was significantly better than simple Chinese traditional drugs [= 4.61, 95%CI (2.18, 9.74),=4.01,<0.000 1], and combination of acupuncture and wes-tern medicines was obviously better than simple western medicines [=3.07, 95%CI(1.24, 7.65),=2.41,=0.02] in the treatment of epilepsy.

CONCLUSION:Acupuncture therapy may have a positive effect in the treatment of epilepsy but the conclusion needs further verification due to very fewer high-quality and well-designed RCTs found at the present.

Curcumin as a hydrophobic polyphenol is extracted from the rhizome of. Curcumin is widely used as a dietary spice and a topical medication for the treatment of inflammatory disorders in Asia. This compound also possesses remarkable anti-inflammatory and neuroprotective effects with the ability to pass from the blood brain barrier. Based on several pharmacological activities of curcumin, it has been introduced as an ideal candidate for different neurological disorders. Despite the pleiotropic activities of curcumin, poor solubility, rapid clearance and low stability have limited its clinical application. In recent years, nano-based drug delivery system has effectively improved the aqueous solubility and bioavailability of curcumin. In this review article, the effects of curcumin nanoparticles and their possible mechanism/s of action has been elucidated in various central nervous system (CNS)-related diseases including Parkinson's disease, Huntington disease, Alzheimer's disease, Multiple sclerosis, epilepsy and Amyotrophic Lateral Sclerosis. Furthermore, recent evidences about administration of nano-curcumin in the clinical trial phase have been described in the present review article.

Dietary therapies represent a potentially valuable adjunct to other epilepsy treatments, such as anticonvulsant medications, epilepsy surgery, and vagus nerve stimulation. Although the ketogenic diet (high fat, adequate protein, low carbohydrate) is the most well-established dietary therapy for epilepsy, other possible approaches include the Atkins diet (high fat, high protein, low carbohydrate), a diet enriched in polyunsaturated fatty acids, or overall restriction of calorie intake. This review discusses the current clinical status of each of these dietary approaches and suggests possible mechanisms by which they might suppress neuronal hyperexcitability and seizures.

The effect of Sahaja yoga meditation on seizure control and electroencephalographic alterations was assessed in 32 patients of idiopathic epilepsy. The subjects were randomly divided into 3 groups. Group I (n = 10) practised Sahaja yoga for 6 months, Group II (n = 10) practised exercises mimicking Sahaja yoga for 6 months and Group III (n = 12) served as the epileptic control group. Group I subjects reported a 62 per cent decrease in seizure frequency at 3 months and a further decrease of 86 per cent at 6 months of intervention. Power spectral analysis of EEG showed a shift in frequency from 0-8 Hz towards 8-20 Hz. The ratios of EEG powers in delta (D), theta (T), alpha (A) and beta (B) bands i.e., A/D, A/D + T, A/T and A + B/D + T were increased. Per cent D power decreased and per cent A increased. No significant changes in any of the parameters were found in Groups II and III, indicating that Sahaja yoga practice brings about seizure reduction and EEG changes. Sahaja yoga could prove to be beneficial in the management of patients of epilepsy.

BACKGROUND:Approximately one-third of patients with epilepsy continue to experience seizures despite adequate therapy with antiepileptic drugs. Drug-resistant epilepsy is even more frequent in subjects with intellectual disability. As a result, several non-pharmacological interventions have been proposed to improve quality of life in patients with intellectual disability and drug-resistant epilepsy. A number of studies have demonstrated that music can be effective at reducing seizures and epileptiform discharges. In particular, Mozart's sonata for two pianos in D major, K448, has been shown to decrease interictal EEG discharges and recurrence of clinical seizures in patients with intellectual disability and drug-resistant epilepsy as well. The aim of this study is to investigate the influence of Mozart's music on seizure frequency in institutionalized epileptic subjects with profound/severe intellectual disability.

SUBJECTS AND METHODS:Twelve patients (10 males and 2 females) with a mean age of 21.6 years were randomly assigned to two groups in a cross-over design; they listened to Mozart K448 once a day for six months.

RESULTS:A statistically significant difference was observed between the listening period and both baseline and control periods. During the music period, none of the patients worsened in seizure frequency; one patient was seizure-free, five had a greater than 50% reduction in seizure frequency and the remaining showed minimal (N=2) or no difference (N=4). The average seizure reduction compared to the baseline was 20.5%. Our results are discussed in relation to data in the literature considering differences in protocol investigation.

CONCLUSIONS:Music may be considered a useful approach as add-on therapy in some subjects with profound intellectual disability and drug-resistant epilepsy and can provide a new option for clinicians to consider, but further large sample, multicenter studies are needed to better understand the characteristics of responders and non-responders to this type of non-pharmacological intervention.

There are hundreds of compounds found in the marijuana plant, each contributing differently to the antiepileptic and psychiatric effects. Cannabidiol (CBD) has the most evidence of antiepileptic efficacy and does not have the psychoactive effects of∆-tetrahydrocannabinol. CBD does not act via cannabinoid receptors and its antiepileptic mechanism of action is unknown. Despite considerable community interest in the use of CBD for paediatric epilepsy, there has been little evidence for its use apart from anecdotal reports, until the last year. Three randomized, placebo-controlled, double-blind trials in Dravet syndrome and Lennox-Gastaut syndrome found that CBD produced a 38% to 41% median reduction in all seizures compared to 13% to 19% on placebo. Similarly, CBD resulted in a 39% to 46% responder rate (50% convulsive or drop-seizure reduction) compared to 14% to 27% on placebo. CBD was well tolerated; however, sedation, diarrhoea, and decreased appetite were frequent. CBD shows similar efficacy to established antiepileptic drugs. WHAT THIS PAPER ADDS: Cannabidiol (CBD) shows similar efficacy in the severe paediatric epilepsies to other antiepileptic drugs. Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD.

BACKGROUND:Epilepsy is one of the chronic and heterogeneous epidemic neurological disorders leading to substantial mortality. The aim of the present study was to investigate the serum levels of malondialdehyde (MDA), vitamin C, and trace elements namely zinc (Zn), copper (Cu), and manganese (Mn) in epileptic patients of Bangladesh and to establish if there are any pathophysiological correlations.

METHODS:This was a case-control study with 40 generalized epileptic patients and 40 healthy subjects as controls. Epilepsy was determined by the presence of seizure events with an abnormal electroencephalography and magnetic resonance imaging report of brain.

RESULTS:Anthropometric parameters highlighted that age is a major risk factor of epilepsy and men are more prone to epilepsy than women. Blood serum analysis demonstrated significantly ( P<.001) higher values of MDA and lower level of vitamin C in the patient group (4.41± 0.76 μmol/mL and 18.31 ± 0.84 μmol/L, respectively) compared with control (1.81 ± 0.70 μmol/mL and 29.72 ± 1.06 μmol/L, respectively). Pearson's correlation analysis revealed a negative correlation between the serum level of MDA and vitamin C for both patient ( r = -0.023, P = .887) and control group ( r = -0.142, P = .383). This study also revealed that the trace elements (Zn, Cu) were significantly ( P<.05) lower in epileptics (68.32± 4.59 and 50.81 ± 2.54 μg/dL, respectively) where the level of Mn in patients (187.71 ± 9.04 μg/dL) was almost similar to that of the control group ( P>.05). The univariate analysis demonstrated that zinc<70μg/dL (odds ratio = 3.56, P<.05) and copper<50μg/dL were associated (odds ratio = 14.73, P<.001) with an increased risk of epilepsy. Establishment of interelement relationship strongly supported that there was a disturbance in the element homeostasis of epileptic patients.

CONCLUSIONS:The study results strengthen the role of lipid peroxidation, antioxidants and trace elements in the pathogenesis and warrant larger studies to investigate the association of these biochemical parameters with epilepsy.

The gut microbiome is emerging as a key regulator of brain function and behavior and is associated with symptoms of several neurological disorders. There is emerging evidence that alterations in the gut microbiota are seen in epilepsy and in response to seizure interventions. In this review, we highlight recent studies reporting that individuals with refractory epilepsy exhibit altered composition of the gut microbiota. We further discuss antibiotic treatment and infection as microbiome-related factors that influence seizure susceptibility in humans and animal models. In addition, we evaluate how the microbiome may mediate effects of the ketogenic diet, probiotic treatment, and anti-epileptic drugs on reducing both seizure frequency and severity. Finally, we assess the open questions in interrogating roles for the microbiome in epilepsy and address the prospect that continued research may uncover fundamental insights for understanding risk factors for epilepsy, as well as novel approaches for treating refractory epilepsy.

Today, neurological disorders such as epilepsy, depression, tardive dyskinesia, and stress, and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, dementia, and Huntington's disease affect millions of people all over the world. Existing pharmacological interventions do not meet the desired therapeutic benefits for a significant number of patients, and hence, numerous research studies are in progress to find novel therapies for these disorders. Herbal drugs, which have been used in traditional medicine for centuries, are also being explored and scientifically evaluated for the treatment of these neurological disorders. While substantial evidence exists for the antioxidant, anti-inflammatory, anti-hyperlipidemic, and anti-hyperglycemic effects of Emblica officinalis, in vivo and in vitro studies, have also revealed its beneficial therapeutic activities in numerous neurological disorders. These diverse neuroprotective pharmacodynamic actions of E. officinalis corroborated by accumulating evidence in pre-clinical research studies deserve the attention of the scientific community to develop viable pharmacotherapeutic strategies. The present review elaborates upon the latest scientific evidence pertaining to the pharmacological effects of E. officinalis in numerous neurological and neurodegenerative disorders and also gives way for future research in this area.

Ganoderma lucidum extracts have shown antiepileptic effects in in vivo and in vitro studies. In this work, primary hippocampal neurons cultured in magnesium-free medium were used to study the neuroprotective effects of ganoderic acid A and B (GA-A and GA-B) on superoxide dismutase (SOD) activity and mitochondrial membrane potential, to improve our understanding of their antiepileptic effect. The activity of SOD was determined by the xanthine oxidase assay, the variations of mitochondrial membrane potential and cell apoptosis were measured by JC-1 fluorescent staining and flow cytometry. It was found that the SOD activity and mitochondrial membrane potential (118.84 U/mg protein and 244.08Δψm) of the epileptic hippocampal neurons were significantly lower than control values (135.95 U/mg protein and 409.81 Δψm), associated with an increase of cell apoptosis (31.88% vs. 8.84%). These circumstances can be improved by treatment of GA-A/GA-B (for SOD, 127.15±3.82 / 120.52±4.30 U/mgprotein; for membrane potential (Δψm), 372.35 / 347.28; and for cell apoptosis (%), 14.93 / 20.52). Results indicated that GA-A significantly improved SOD activity, while both GA-A/GA-B tranquillized the mitochondrial membrane potential of hippocampal neurons, and thereby protected these neurons by inhibiting apoptosis.

The high-fat ketogenic diet (KD) is a remarkably effective treatment for medically intractable epilepsy and has been part of the clinical armamentarium for nearly a century. However, the mechanisms underlying the KD's actions have remained elusive. Over the past decade, there has been phenomenal international growth of clinical centers offering metabolism-based therapies for epilepsy, and rapidly expanding research into the cellular and biochemical effects induced by the KD. At present, there are many hypotheses regarding KD action, and while each is uniquely compelling, it is becoming more apparent that the KD likely works through multiple mechanisms that target fundamental biochemical pathways linked to cellular substrates (e.g., ion channels) and mediators responsible for neuronal hyperexcitability. This is not altogether surprising given the complexity of the epileptic brain, and the many different pathophysiologic mechanisms that underlie seizure genesis and epileptogenicity. The scientific literature involving the KD strongly supports the notion that epilepsy may indeed in part represent a"metabolic disease", and that this concept could serve as a novel framework for the development of more effective anti-seizure drugs.

Background:Even with the extensive use of ketogenic dietary therapies (KD), there still exist many areas of the world that do not provide these treatments. Implementing the ketogenic diet in different countries forms a real challenge in order to match the cultural and economic differences.

Aim:To assess the feasibility of implementing a ketogenic diet plan in a limited resource setting with identification of the compliance, tolerability and side effects in the target population and to assess the efficacy of the ketogenic diet in children with intractable epilepsy.

Method of the study:The medical records of 28 patients with intractable epilepsy, treated at The Children's Hospital - Cairo University from December 2012 to March 2014 with ketogenic dietary therapy were reviewed. The non-fasting protocol was followed without hospital admission. All children were started on a standardized classic ketogenic diet with a ratio ranging from 2.5-4:1 (grams of fat to combined carbohydrate and protein). Patients were followed at 1, 3 and 6 months after diet initiation.

Results:The median age was 60 months (range, 30-110). After 1 month from diet initiation, 16 patients (57%) remained on the diet. One of them (6.3%) had more than 90% reduction in seizure frequency, an additional 6 patients (37.5%) had a 50-90% reduction in seizure frequency. In total, seven out of the 16 patients continuing the diet for 1 month (43.8%) had more than 50% improvement in seizure control from the base line. Despite having 50-90% seizure control, three children discontinued the diet after one month.Three months after diet initiation, 6 patients (22%) remained on diet, 4 of them (66.7%) had more than 50%reduction in seizure frequency.At 6 months, only 3 patients remained on diet, 2 of them (66.6%) had 50-90% reduction in seizure frequency, while one patient (33.3%) showed better than 90% decrease in seizure.

Conclusion:The current study shows that the ketogenic diet could be implemented in medium resources countries and should be included in the management of children with intractable epilepsy.

Background. Approximately, one-third of patients with epilepsy are refractory to pharmacological treatment which mandates extensive medical care and imposes significant economic burden on patients and their societies. This study intends to assess the impact of the treatment with ketogenic diet (KD) on reducing seizure-related emergency room visits and hospitalizations in children with refractory epilepsy. Methods. This is a retrospective review of children treated with the KD in one tertiary center. We compared a 12 months' period prior to KD with 12 months after the diet was started in regard to the number of emergency department (ED) visits, hospitalizations, and hospital days as well as their associated charges. Results. 37 patients (57% males) were included. Their ages at time of KD initiation were (4.0± 2.78) years. Twelve months after the KD initiation, the total number of ED visits was reduced by 36% with a significant decrease of associated charges (p = 0.038). The number of hospital admissions was reduced by 40% and the number of hospital days was reduced by 39%. The cumulative charges showed net cost savings after 9 months when compared to the prediet baseline. Conclusion. In children with refractory epilepsy, treatment with the ketogenic diet reduces the number of ED visits and hospitalizations and their corresponding costs.

The ketogenic diet (KD), a high-fat, low-carbohydrate, and adequate-protein diet is an established, effective nonpharmacologic treatment option for intractable childhood epilepsy. The KD was developed in 1921 and even though it has been increasingly used worldwide in the past decade, many neurologists are not familiar with this therapeutic approach. In the past few years, alternative and more flexible KD variants have been developed to make the treatment easier and more palatable while reducing side effects and making it available to larger group of refractory epilepsy patients. This review summarizes the history of the KD and the principles and efficacy of the classic ketogenic diet, medium-chain triglyceride(s) (MCT) ketogenic diet, modified Atkins diet, and low glycemic index treatment.

INTRODUCTION:Ketogenic diet is a low carbohydrate diet, which can be used as a treatment for refractory childhood epilepsy. The first aim of this study was to evaluate its efficacy, in patients receiving ketogenic diet for at least three months, on epilepsy control, behaviour and awareness. The secondary aims were to evaluate the variation in the number of antiepileptic drugs, reasons for discontinuing the diet and adverse effects.

MATERIAL AND METHODS:Retrospective analysis of clinical records of patients who underwent ketogenic diet for refractory epilepsy, from October 2007 to January 2018, in a tertiary pediatric hospital.

RESULTS:In the twenty-nine eligible patients, the mean age of initiation was 7.9 years-old (+/- 5.6). Of those, 18 had a≥ 50% reduction of seizure activity, 19 a marked behaviour improvement and 18 improved awareness. The median number of antiepileptic drugs remained equal for the 15 patients who completed 18 months of treatment (three drugs). The main reason for discontinuing ketogenic diet was a familiar decision. The main adverse effects were hypercholesterolemia (n = 23) and hypertriglyceridemia (n = 21).

DISCUSSION:Results were comparable to those of other cohorts, namely age of initiation, proportion of patients completing ketogenic diet, most frequent reasons for stopping and significant improvement of alertness and behavior.

CONCLUSION:Beyond seizure control, patients experienced a marked improvement in behavior and awareness. It is necessary to develop strategies to increase the adherence of families to the diet.

BACKGROUND AND PURPOSE:In the present study, we reviewed the outcome of ketogenic diet (KD) use for the management of epilepsy in children with tuberous sclerosis complex (TSC).

METHODS:A total of 12 children with intractable epilepsy associated with TSC who were treated with KD at our hospital between March 1, 2008 and February 28, 2015 were retrospectively enrolled.

RESULTS:The mean age at the time of KD initiation was 73.1± 38.0 months. Patients were medically refractory to a mean of 4.8 ± 1.7 antiepileptic drugs. Nine patients (75.0%) had a history of infantile spasms. At 3 months after KD initiation, 10 patients (83.3%) had>50% seizure reduction. Moreover, 7 patients (58.3%) exhibited qualitative improvements in cognition and behavior after KD initiation, as reported by caregivers/parents. The mean duration of dietary therapy was 14.8± 12.8 months. Half of the patients in this study eventually underwent epilepsy surgery due to persistent seizures or seizure relapse.

CONCLUSION:KD is an important non-pharmacological treatment option for patients with intractable epilepsy associated with TSC. KD may improve cognition and behavior in addition to reducing seizure frequency.

The ketogenic diet (KD) is used for the treatment of refractory epilepsy in children, however, the mechanism(s) remains largely unknown. Also, the antiepileptogenic potential in animal models of epilepsy has been poorly addressed. Activation of cannabinoid type-1 receptor (CB(1)-R) upon seizure activity may mediate neuroprotection as may several N-acylethanolamines. It is unknown how the KD interfere with the endocannabinoid system. We investigated the antiepileptogenic potential of the KD in the pentylenetetrazole kindling model in young mice and measured the hippocampal levels of CB(1)-R by Western blot and of endocannabinoids and N-acylethanolamines by mass spectrometry. The KD significantly decreased incidence and severity of seizures, and significantly increased the latency to clonic convulsions. There were no changes in levels of endocannabinoids or CB(1)-R expression by either seizure activity or type of diet. The level of oleoylethanolamide as well as the sum of N-acylethanolamines were significantly decreased by the KD, but were unaffected by seizure activity. The study shows that the KD had clear antiepileptogenic properties in the pentylenetetrazole kindling model and does not support a role of endocannabinoids in this model. The significance of the decreased hippocampal level of oleoylethanolamide awaits further studies.