Plasma fatty acid abnormality in Sudanese drug-resistant epileptic patients.

Intervention studies have demonstrated that the n-3 fatty acids, docosahexaenoic and eicosapentaenoic acids, ameliorate seizure frequency in patients with drug-resistant epilepsy (DRE). There is a scarcity of fatty acid status of patients with epilepsy. We have investigated blood fatty acids of patients with DRE and assessed the indices of elongase and desaturase activities. DRE patients (n = 83) and healthy controls (n = 31) were recruited form Soba University Hospital Neurology Referral Clinic and Ibn-Auf paediatric Teaching Hospital Neurology Referral Clinic, Khartoum, Sudan. Fatty acid composition of plasma total lipids, phosphatidylcholine and neutral lipids were analysed. The patients compared with their healthy counterparts had higher levels of C14:0, C16:0, C18:0, C20:0, C22:0 (p<0.05) and C24:0, and total saturates (p<0.05). Similarly, the proportions of C16:1n-7, 18:1n-7, C18:1n-9, C20:1n-9, C24:1n-9 and total monounsaturated fatty acids; p<0.005) were higher in the drug-resistant patients. Conversely, the patients had lower levels of n-6 (C18:2n-6, C18:3n-6, C20:4n-6, n-6 metabolites and total n-6; p<0.005 and C20:2n-6 and C20:3n-6; p<0.05) and n-3 (C20:5n-3, C22:5n-3, C22:6n-3, ∑EPA and DHA, n-3 metabolites and total n-3; p<0.05) fatty acids. Indices of elongase and desaturase activities - The plasma total lipid ratios of C16:0/C14:0 (p = 0.001), C18:0/C16:0 (p = 0.001), C16:1n-7/C16:0 (p = 0.027), C18:1n-9/C18:0 (p = 0.022) and C22:4n-6/C20:4n-6 (p = 0.008) were higher and C18:3n-6/C18:2n-6 (p = 0.05), C20:4n-6/C20:3n-6 (p = 0.032) and C20:4n-6/C18:2n-6 (p>0.05) lower in the patients with drug-resistant epilepsy than in the healthy control subjects. DRE is associated with blood fatty acid perturbation and abnormal activities of long-chain fatty acid elongase (ELOVL-6), stearoyl-coenzyme A desaturase-1 (SCD-1), delta 6-fatty acid desaturase (D6D) and delta 5 fatty acid desaturase (D5D). N-3 fatty acids are known to ameliorate seizures frequency and dampen neuronal hyperexcitability. Therefore, patients with DRE should be regularly monitored and, if necessary, supplemented with n-3 fatty acids.

Barriers in accessing medical cannabis for children with drug-resistant epilepsy in Canada: A qualitative study.

INTRODUCTION: The use of medical cannabis to treat drug-resistant epilepsy in children is increasing; however, there has been limited study of the experiences of parents with the current system of accessing medical cannabis for their children. METHODS: In this qualitative study, we used a patient-centered access to care framework to explore the barriers faced by parents of children with drug-resistant epilepsy when trying to access medical cannabis in Canada. We conducted semistructured interviews with 19 parents to elicit their experiences with medical cannabis. We analyzed the data according to five dimensions of access, namely approachability, acceptability, availability, affordability, and appropriateness. RESULTS: Parents sought medical cannabis as a treatment because of a perceived unmet need stemming from the failure of antiepileptic drugs to control their children's seizures. Medical cannabis was viewed as an acceptable treatment, especially compared with adding additional antiepileptic drugs. After learning about medical cannabis from the media, friends and family, or other parents, participants sought authorization for medical use. However, most encountered resistance from their child's neurologist to discuss and/or authorize medical cannabis, and many parents experienced difficulty in obtaining authorization from a member of the child's existing care team, leading them to seek authorization from a cannabis clinic. Participants described spending up to $2000 per month on medical cannabis, and most were frustrated that it was not eligible for reimbursement through public or private insurance programs. CONCLUSIONS: Parents pursue medical cannabis as a treatment for their children's drug-resistant epilepsy because of a perceived unmet need. However, parents encounter barriers in accessing medical cannabis in Canada, and strategies are needed to ensure that children using medical cannabis receive proper care from healthcare professionals with training in epilepsy care, antiepileptic drugs, and medical cannabis.

Neural stimulation systems for the control of refractory epilepsy: a review.

Epilepsy affects nearly 1% of the world's population. A third of epilepsy patients suffer from a kind of epilepsy that cannot be controlled by current medications. For those where surgery is not an option, neurostimulation may be the only alternative to bring relief, improve quality of life, and avoid secondary injury to these patients. Until recently, open loop neurostimulation was the only alternative for these patients. However, for those whose epilepsy is applicable, the medical approval of the responsive neural stimulation and the closed loop vagal nerve stimulation systems have been a step forward in the battle against uncontrolled epilepsy. Nonetheless, improvements can be made to the existing systems and alternative systems can be developed to further improve the quality of life of sufferers of the debilitating condition. In this paper, we first present a brief overview of epilepsy as a disease. Next, we look at the current state of biomarker research in respect to sensing and predicting epileptic seizures. Then, we present the current state of open loop neural stimulation systems. We follow this by investigating the currently approved, and some of the recent experimental, closed loop systems documented in the literature. Finally, we provide discussions on the current state of neural stimulation systems for controlling epilepsy, and directions for future studies.

Status Epilepticus, Refractory Status Epilepticus, and Super-refractory Status Epilepticus.

PURPOSE OF REVIEW: Status epilepticus, refractory status epilepticus, and super-refractory status epilepticus can be life-threatening conditions. This article presents an overview of the three conditions and discusses their management and outcomes. RECENT FINDINGS: Status epilepticus was previously defined as lasting for 30 minutes or longer but now is more often defined as lasting 5 minutes or longer. A variety of potential causes exist for status epilepticus, refractory status epilepticus, and super-refractory status epilepticus, but all three ultimately involve changes at the cellular and molecular level. Management of patients with status epilepticus generally requires several studies, with EEG of utmost importance given the pathophysiologic changes that can occur during the course of status epilepticus. Status epilepticus is treated with benzodiazepines as first-line antiepileptic drugs, followed by phenytoin, valproic acid, or levetiracetam. If status epilepticus does not resolve, these are followed by an IV anesthetic and then alternative therapies based on limited data/evidence, such as repetitive transcranial magnetic stimulation, therapeutic hypothermia, immunomodulatory agents, and the ketogenic diet. Scores have been developed to help predict the outcome of status epilepticus. Neurologic injury and outcome seem to worsen as the duration of status epilepticus increases, with outcomes generally worse in super-refractory status epilepticus compared to status epilepticus and sometimes also to refractory status epilepticus. SUMMARY: Status epilepticus can be a life-threatening condition associated with multiple complications, including death, and can progress to refractory status epilepticus and super-refractory status epilepticus. More studies are needed to delineate the best management of these three entities.

Medical cannabis: A needs analysis for people with epilepsy.

BACKGROUND AND PURPOSE: Medical cannabis may be effective treatment for refractory epilepsy. It is timely to seek users' and potential users' opinions in regard to its place in the management of epilepsy. MATERIALS AND METHODS: An online survey was administered to members of an epilepsy support organisation in Western Australia. Experience with cannabis for management of epilepsy was explored, along with desire to trial a particular pharmaceutical formulation(s). RESULTS: People with epilepsy (33/71) and carers (38/71) participated. Fifty-four participants indicated no experience with medical cannabis, although 35, mainly with inadequate response to prescription medicines, were willing to ask for a prescription. Concerns included difficulty accessing cannabis and high cost of this treatment. Tablets/capsules was the most acceptable dosage form for development. CONCLUSION: These findings suggest wide interest in trialling medical cannabis in individual cases of refractory epilepsy, despite the developing body of literature and some concerns about cost and procurement.

Cannabis for paediatric epilepsy: challenges and conundrums.

Research is expanding for the use of cannabidiol as an anticonvulsant drug. The mechanism of cannabidiol in paediatric epilepsy is unclear but is thought to play a role in modulation of synaptic transmission. Evidence for its efficacy in treating epilepsy is limited but growing, with a single pharmaceutical company-funded randomised double-blind controlled trial in children with Dravet syndrome. Progress towards the use of medicinal cannabinoids incorporates a complex interplay of social influences and political and legal reform. Access to unregistered but available cannabidiol in Australia outside of clinical trials and compassionate access schemes is state dependent and will require Therapeutic Goods Administration approval, although the cost may be prohibitive. Further clinical trials are needed to clearly define efficacy and safety, particularly long term.

The current status of artisanal cannabis for the treatment of epilepsy in the United States.

The widespread patient use of artisanal cannabis preparations has preceded quality validation of cannabis use for epilepsy. Neurologists and cannabinoid specialists are increasingly in a position to monitor and guide the use of herbal cannabis in epilepsy patients. We report the retrospective data on efficacy and adverse effects of artisanal cannabis in Patients with medically refractory epilepsy with mixed etiologies in Washington State, California, and Maine. Clinical considerations, including potential risks and benefits, challenges related to artisanal preparations, and cannabinoid dosing, are discussed. RESULTS: Of 272 combined patients from Washington State and California, 37 (14%) found cannabis ineffective at reducing seizures, 29 (15%) experienced a 1-25% reduction in seizures, 60 (18%) experienced a 26-50% reduction in seizures, 45 (17%) experienced a 51-75% reduction in seizures, 75 (28%) experienced a 76-99% reduction in seizures, and 26 (10%) experienced a complete clinical response. Overall, adverse effects were mild and infrequent, and beneficial side effects such as increased alertness were reported. The majority of patients used cannabidiol (CBD)-enriched artisanal formulas, some with the addition of delta-9-tetrahydrocannabinol (THC) and tetrahydrocannabinolic acid (THCA). Four case reports are included that illustrate clinical responses at doses <0.1mg/kg/day, biphasic dose-response effects, the use of THCA for seizure prevention, the use of THC for seizure rescue, and the synergy of cannabinoids and terpenoids in artisanal preparations. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".

An Australian nationwide survey on medicinal cannabis use for epilepsy: History of antiepileptic drug treatment predicts medicinal cannabis use.

Epilepsy Action Australia conducted an Australian nationwide online survey seeking opinions on and experiences with the use of cannabis-based products for the treatment of epilepsy. The survey was promoted via the Epilepsy Action Australia's main website, on their Facebook page, and by word of mouth. The survey consisted of 39 questions assessing demographics, clinical factors, including diagnosis and seizure types, and experiences with and opinions towards cannabis use in epilepsy. A total of 976 responses met the inclusion criteria. Results show that 15% of adults with epilepsy and 13% of parents/guardians of children with epilepsy were currently using, or had previously used, cannabis products to treat epilepsy. Of those with a history of cannabis product use, 90% of adults and 71% of parents reported success in reducing seizure frequency after commencing cannabis products. The main reasons for medicinal cannabis use were to manage treatment-resistant epilepsy and to obtain a more favorable side-effect profile compared to standard antiepileptic drugs. The number of past antiepileptic drugs tried was a significant predictor of medicinal cannabis use in both adults and children with epilepsy. Fifty-six percent of adults with epilepsy and 62% of parents/guardians of children with epilepsy expressed willingness to participate in clinical trials of cannabinoids. This survey provides insight into the use of cannabis products for epilepsy, in particular some of the likely factors influencing use, as well as novel insights into the experiences of and attitudes towards medicinal cannabis in people with epilepsy in the Australian community. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".

Medicinal marijuana for epilepsy: a case series study.

OBJECTIVE: To describe the social, clinical and use-patterns characteristics of medicinal marijuana use among patients with epilepsy (PWEs). METHODS: Eighteen PWEs with prescriptions for medicinal marijuana from a Canadian adult-epilepsy clinic were included in this study. RESULTS: Eighteen patients had a prescription of medicinal marijuana from a total population of 800 PWEs in our center (2.2%). Mean age of patients was 30±7.4 (19-50) years. Twelve (67%) patients were males. Eleven (61%) patients had drug-resistant epilepsy. Eleven (61%) patients suffered a psychiatric comorbidity and reported the use of illicit substances or heavy alcohol or tobacco consumption. Only two (11%) patients were married; the rest of patients (89%) were single or divorced. The drug use pattern was similar among patients. All patients asked for marijuana permission in the epilepsy clinic. Most (83%) had a previous history of marijuana smoking, with a mean of 6.6±3 (1-15) years. The mean consumption dose was 2.05±1.8 (0.5-8) grams per day. Ten (56%) patients reported withdrawal seizure exacerbation when they stopped the marijuana. Only two patients (11%) reported side effects, and all patients found medicinal marijuana very helpful for seizure control and improvement of mood disorder. CONCLUSIONS: PWEs using medicinal marijuana have a common profile. They are usually young single men with drug-resistant epilepsy and psychiatric comorbidity. Most used marijuana before formal prescription and all believe the drug was effective on their seizure control. Because of the concurrent use of other antiseizure medications, it is complex to estimate the actual effect of marijuana.