Posts Tagged Epilepsy

[Editorial] New Directions in the Management of Status Epilepticus – Neurology

Status Epilepticus (SE) is a neurological emergency and has high morbidity and mortality. The International League Against Epilepsy (ILAE) recently updated their definition to specify that, “SE is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures.” Such phenomena can lead to long-term neurological complications due to neuronal death, glia, neurological injury, aberrant neuroplasticity, oxidative stress and inflammation, and alteration of neuronal networks. Depending upon the type and duration of SE, these mechanisms are quite variable. Therefore, in response to the updated definition of SE, novel avenues of research are required to address the specified involvement of the underlying mechanisms and pathophysiology resulting in the development of and outcomes from SE.

Improving the basic science understanding of SE will facilitate essential clinical trials. One can envision such experiments to include device and compound-based technological interventions directed at aborting the seizure activity and improving clinical outcomes. Benzodiazepines remain one of the cornerstones of treatment, and studies are underway to study new delivery options, including intranasal, buccal, and intramuscular midazolam, in addition to rectal diazepam, with the goal of aborting the seizure activity outside the hospitals, as rapidly as possible. Approved and off-label anticonvulsants, such as phenytoin, phenobarbital, valproate, topiramate, levetiracetam, lacosamide, steroids, immunosuppressants, and neuroprotective compounds, have also shown some efficacy at treating SE. However, substantial challenges remain in optimally managing SE and minimizing the short- and long-term complications. Such difficulties can be overcome by innovative approaches targeting the underlying mechanisms of neuronal excitability, glia, neuronal death, neuroplasticity, oxidative stress, inflammation, and neuroinflammation.

The book comprises six original research articles and four reviews. Collectively, the materials provide insights into the pathophysiology, clinical presentation, treatment, recent advances and future directions in the management of SE, with the goal of providing an in-depth view and advancing the field to improve management of SE.

The book opens with an original research article by Kristin Phillips et al. which showed the role of hypothermia as a neuroprotective agent for preventing the development of calcium plateau against SE-induced delayed hippocampal injury. Hypothermia-mediated neuroprotection after pilocarpine-induced SE was evident from decreased Fluoro-Jade C+ neurons in the hippocampus. The second original article by Matos et al. described SE-induced changes in spontaneous locomotor activity and the temporal expression of genes related to circadian rhythms (Clock, Bmal1, Cry1, Cry2, Per1, Per2, and Per3) in the hippocampus at both early post-SE and chronic epilepsy phases. Authors propose that seizures can act as a non-photic cue and altered temporal expression of clock genes likely contributes to the pathogenesis of mesial temporal lobe epilepsy. The third original article by Hutson et al. presented an interesting case study which showed evidence of brain dynamics resetting after successful anticonvulsant treatment following SE utilizing stereo encephalography (SEEG) data.

A review by Kirmani et al. conferred the current literature about autoimmune SE including therapeutic options and future directions. An original research article by Wyatt-Johnson et al. reported that SE-induced morphological alterations in microglia at different time-points and discussed the role of such changes on epileptogenesis. Another research article by Kortland et al. addressed the socioeconomic outcome and quality of life outcome in adults after status epilepticus in their original article. The authors conducted a multicenter, longitudinal, matched case-control analysis and concluded that relatively favorable outcomes seen in patients with refractory and super refractory SE as compared to non-refractory SE cases underlying the need of effective therapeutic choices.

An original research article by Bertoglio et al. compared the effects of two different protocols of kainate-induced SE in two strains of rats on neurodegeneration and chronic epilepsy development. The findings revealed that severe neuron loss after SE does not necessarily correlate with a higher seizure rate in the chronic phase after SE. In a review article, Castro et al. discussed the efficacy and promise of resveratrol, a phytoalexin found in the skin of red grapes, for easing SE-induced neurodegeneration, neuroinflammation, aberrant neurogenesis and for restraining the evolution of SE-induced brain injury into a chronic epileptic state. Sharma et al. by reviewing methods of induction and characterization of behavioral SE and EEG correlates in mice and rats, highlighted the advantages of a repeated low dose of kainate protocol for minimizing the variability in the initial SE severity and reducing the mortality rate. The last original article by Lucchi et al. described the role peroxisome proliferator-activated receptor gamma in the anticonvulsant properties of EP-80317, a Ghrelin receptor antagonist in pilocarpine-induced SE rat model and repeated 6 Hz corneal stimulation model in mice.

via Frontiers | Editorial: New Directions in the Management of Status Epilepticus | Neurology

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[Abstract] Antiepileptic drug treatment during pregnancy and delivery in women with epilepsy – A retrospective single center study


Pregnancies in women with epilepsy (WWE) increased significantly during our 11-year study period (41% increase).

Twelve different AEDs were prescribed to WWE during pregnancies in the 11-year period investigated (2005-2015) with Lamotrigine (36.1%), Carbamazepine (25.0%), and Valproic Acid (13.5%) most commonly used.

Valproic acid use was markedly reduced comparing the years 2005-2010 (18.4%) and 2011-2015 (9.4%), a reduction of 48%.

Unfortunately, a trend towards an increase in treating WWE with more than one AED was observed.

Cover image Epilepsy ResearchAbstract


Antiepileptic drugs (AED) are among the most common teratogenic drugs prescribed to women of childbearing age. During pregnancy, the risk of seizures has to be weight against the use of AED treatment. Primary goal was to observe and describe AED treatment policy and its changes during an eleven-year period at our third referral center.


We scrutinized the medical health records for all cases of female epileptic patients admitted for labor at the Rabin Medical Center during the years 2005 – 2015.


A total of 296 deliveries were recorded with 136 labors occurring in the period 2005-2010 (22.7/y) and 160 in 2011-2015 (32.0/y; increase of 41%). Twelve different AEDs were prescribed to WWE during pregnancies in the 11-year period investigated (2005-2015). Most commonly used AEDs during pregnancy were Lamotrigine (36.1%), Carbamazepine (25.0%), and Valproic Acid (13.5%). Comparing their use during the years 2005-2010 and 2011-2015, Lamotrigine (35.3% vs. 36.9%) and Carbamazepine use (23.5% vs. 26.0%) increased slightly. Valproic acid use was markedly reduced in the second period: 18.4% in the years 2005-2010 lowered to 9.4% during 2011-2015, a reduction of 48%. Unfortunately, a trend towards an increase in treating WWE with more than one AED was observed.


The proportion of WWE treated with VPA during pregnancy was significantly reduced in the observed period (2005-2015). Change in fetal outcome during this period for WWE could not be detected.

via Antiepileptic drug treatment during pregnancy and delivery in women with epilepsy—A retrospective single center study – ScienceDirect

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[WEB SITE] What one piece of advice would you give to someone who has just been diagnosed? – Epilepsy Society

21 November 2018

In September 2018, we asked our Facebook community what was the one piece of advice they would want to give to someone who had just been diagnosed with epilepsy. Our Marketing and Communications Executive, Paige Dawkins, talks more about the responses we received.


What one piece of advice would you give to someone who has just been diagnosed?

How can a diagnosis feel?

Everyone will have their own unique reaction to being diagnosed with epilepsy. Some people will feel scared, some people will feel confused as to where the epilepsy came from, possibly seemingly out of the blue. Some people will feel relief, as they finally have an answer to the seizures they have been experiencing. Coming to terms with a diagnosis can depend on someone’s own personal life experiences, as well as the support and information they have available to them at the time, from family, friends, and healthcare professionals.

One thing that we learnt from our Facebook post was for certain – a diagnosis of epilepsy does not necessarily mean the end of an enjoyable and fulfilling life. For some people, their experiences with epilepsy have actually taught them valuable lessons, and for others, epilepsy has not stopped them from achieving their dreams. Below is a selection from over 130 comments we received on the post; here is the advice that our followers would give to someone who has just been diagnosed with epilepsy.

Our follower’s advice

‘Actually I have 2, 1 to the person and the 2nd to the care givers:  1) The biggest problem with Epilepsy is not seizures its other people and their perceptions/attitude. 2) parents,guardians & carers go against you natural instincts and dont wrap someone up in cotton wool. Give them space to grow learn and make mistakes the usual way. Yes its tough on you as you will invariably have to pick up the pieces but it will be invaluable to the child/individual as they will learn not to be defined and constrained by their condition.’

‘never let your epilepsy beat you I got diagnosed 8 years ago I have a one year old baby I work and live a normal everyday life I’ve ran half marathons done the tough mudder and more events I thought things were going to be awful and went to a size 16 I’m now a size 10.’

‘I hate it !! But I’ve learnt to live with it. Don’t let it dictate your life x’

‘Don’t panic. Work with it, not against it.’

‘I have just recently been diagnosed with TLE and the hardest thing I’ve had to deal with is losing my driving licence which has been a complete life changer and very stressful at times. But I still believe you can still be happy as anyone else. You are just going to be living a bit differently from now on. And it’s ok to feel crap about it xxx’

‘Take each day as it comes and treat today as the gift it is…the present.’

‘That it’s not the end of the world. It just feels like it. But you will come to accept it and manage it the best that you can. That it’s more common than you think. And that it does not define who you are x’

‘Don’t fight the people around you who are trying to help, my big mistake.’

‘I’ve had epilepsy all my life, from the age of 18 months and I’m 34 this week. The one thing I would say is. Epilepsy is part of who you are. It’s a sucker, we learn differently and act differntly but we still human. Don’t let people think epilepsy is a big tabo to talk about. Coz it’s not.’

‘Make sure you get an appointment with a neurologist. They have a much better chance of helping you control your epilepsy than a GP.’

‘it means you have to do some thing differently sometimes but it will only stop you living your life if you let. You find your own coping mechanisms, I have a dark sense of humour that freaks people out sometimes if they aren’t used to me.’

‘Always look for the positive, get to know your body & brain. Stay away from booze.’

‘Just roll with it as best you can! The more you stress or get frustrated it just makes it worse and doesn’t get you anywhere. It’s hard when others don’t understand but don’t push them away most of the time they are doing there best x’

‘Do not let it take over your life. You will learn to adapt to certain restrictions life brings with epilepsy…but you can still have a fulfilled life in other ways. Just take care of yourself and be sensible with your decisions’

‘Remember to take the meds…and on time. ‘

‘People don’t understand what its like to think is it going to happen today, that feeling of just wanting to stay at home just incase, but you have to get past this and get help from others in the same position as yourself, joining my local epilepsy coffee and chat group has made me realise that there are people worse off than me and that I’ve just got to get on with it, not being able to drive is crap, it effects the whole family not just myself, I have really low days but just put on a brave face and get on with it! Don’t let it stop you living!’

‘Keep positive…life gets better x’

‘To know your not alone and to know it is good to talk. Xx’

‘Trust yourself and your body. You know your body better than anyone else possibly could. Try not to blame yourself. And for me that’s still really hard. Don’t give up. It’s not easy and is most definitely a life changer. But just love yourself as much as you can with all the trials and all the not knowings. The brain is a largely uncharted map and in hard times lean on that, on the people who truly love you and peace wherever it may be. And through your journey, as hard as it may be eliminate those who are negative and unsupportive. Educate yourself and others in your life and last but not least; the brain is a muscle too and it needs to be worked out. Keep on keeping on’

‘Don’t bottle your feelings up, talk to people who have epilepsy, it really helps a lot. Join epilepsy groups xx’

‘Take your meds regularly. Don’t skip them but if the side effects are unbearable, you CAN request to try a new drug. What is great for one person is terrible for another. Get the right drug for you.’

‘You are not alone x’

‘Get your free bus pass!’

‘It is still who you are. It teaches you to respect your body and pay attention to its signs. It makes you stronger while you have to talk about it to several people, sometimes ask for help… You can live a perfect life with epilepsy :)’

‘Don’t let it define you as a person, it’s only a part of you not all of you’

‘Be kind to yourself.’

‘Take your meds at the same time each day, get enough sleep and keep stress as low as possible. Don’t live in fear of having a seizure (easy to say but hard in reality) and try and live your life to the full.’

‘Try take it all in and learn about the medication and your triggers what starts it off and after that live your life to the best you can do. Dont let it become a label and drag you down rise above it and be yourself xxxx’

‘Talk , cry , love but most of all laughter has helped us stay positive’

‘Take every day as it comes! But don’t let epilepsy define you. The epilepsy society packs are amazing too so definately get yourself a few of those, and especially the just diagnosed pack – they help so much!!’

‘Just don’t give up on anything. You can live a full life with the right medication. And the most important thing: here you’re not alone.’

‘Patience. It’s a bumpy ride so keep strong. ‘

‘Research other people’s triggers. What’s okay for one person may not be for you. Sewing actually triggers me. (Focusing on Fast patterns)’

‘Sleep is important! Too little sleep can make seizures worse. While sleep can really help post siezure recovery.’

‘I know it’s hard, but please don’t give up. Don’t let epilepsy rule your life! ‘

‘You have just started a new chapter in your life. Epilepsy is not how you are, it is what you have. Be patient and learn what your body is telling you’

‘Hey plenty of rest and keep a regular routine with eating / sleeping xo’

‘Don’t panic. it’s not the end of the world and you can live a normal life’

‘It isn’t always life changing. The right meds might be the first you try x’

‘There are always better days. Relax and accept the dark days and know they’ll not last forever.’

‘Do not let it change your dreams goals & plans in life. It’s a condition we have to live with not let it rule our life. I have never let it get the better of me or my dreams goals & plans. I am a husband a dad run my own businesses stood as an independent candidate in last years general election! A personal goal from a young age. Epilepsy is not the end of your life journey it’s part of it!’

Our online social community

On our social media pages, we share information about epilepsy, news stories, blogs, personal stories and community posts such as the above. If you would like to join our online community, follow us on FacebookTwitterInstagram and LinkedIn.

via What one piece of advice would you give to someone who has just been diagnosed?

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[Abstract + References] Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis



Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels, neurotransmitter transporters, and multiple 7-transmembrane receptors. In contrast to tetra-hydrocannabinol, CBD lacks psychoactive properties, does not produce euphoric or intrusive side effects, and is largely devoid of abuse liability.


The aim of the study was to estimate the efficacy and safety of CBD as adjunctive treatment in patients with epilepsy using meta-analytical techniques.


Randomized, placebo-controlled, single- or double-blinded add-on trials of oral CBD in patients with uncontrolled epilepsy were identified. Main outcomes included the percentage change and the proportion of patients with ≥ 50% reduction in monthly seizure frequency during the treatment period and the incidence of treatment withdrawal and adverse events (AEs).


Four trials involving 550 patients with Lennox–Gastaut syndrome (LGS) and Dravet syndrome (DS) were included. The pooled average difference in change in seizure frequency during the treatment period resulted 19.5 [95% confidence interval (CI) 8.1–31.0; p = 0.001] percentage points between the CBD 10 mg and placebo groups and 19.9 (95% CI 11.8–28.1; p < 0.001) percentage points between the CBD 20 mg and placebo arms, in favor of CBD. The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07–2.88; p = 0.025]. Across the trials, drug withdrawal for any reason occurred in 11.1% and 2.6% of participants receiving CBD and placebo, respectively (RR 3.54, 95% CI 1.55–8.12; p = 0.003) [Chi squared = 2.53, degrees of freedom (df) = 3, p = 0.506; I2 = 0.0%]. The RRs to discontinue treatment were 1.45 (95% CI 0.28–7.41; p = 0.657) and 4.20 (95% CI 1.82–9.68; p = 0.001) for CBD at the doses of 10 and 20 mg/kg/day, respectively, in comparison to placebo. Treatment was discontinued due to AEs in 8.9% and 1.8% of patients in the active and control arms, respectively (RR 5.59, 95% CI 1.87–16.73; p = 0.002). The corresponding RRs for CBD at the doses of 10 and 20 mg/kg/day were 1.66 (95% CI 0.22–12.86; p = 0.626) and 6.89 (95% CI 2.28–20.80; p = 0.001). AEs occurred in 87.9% and 72.2% of patients treated with CBD and placebo (RR 1.22, 95% CI 1.11–1.33; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.


Adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo.


  1. 1.
    Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R. How common are the “common” neurologic disorders? Neurology. 2007;68:326–37.CrossRefGoogle Scholar
  2. 2.
    Cagnetti C, Lattanzi S, Foschi N, Provinciali L, Silvestrini M. Seizure course during pregnancy in catamenial epilepsy. Neurology. 2014;83:339–44.CrossRefGoogle Scholar
  3. 3.
    Cockerell OC, Johnson AL, Sander JW, Hart YM, Shorvon SD. Remission of epilepsy: results from the national general practice study of epilepsy. Lancet. 1995;346:140–4.CrossRefGoogle Scholar
  4. 4.
    Lattanzi S, Zaccara G, Giovannelli F, Grillo E, Nardone R, Silvestrini M, et al. Antiepileptic mono-therapy in newly diagnosed focal epilepsy. A network meta-analysis. Acta Neurol Scand. (Epub 2018 Sep 8).
  5. 5.
    Lattanzi S, Cagnetti C, Foschi N, Provinciali L, Silvestrini M. Lacosamide monotherapy for partial onset seizures. Seizure. 2015;27:71–4.CrossRefGoogle Scholar
  6. 6.
    Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342:314–9.CrossRefGoogle Scholar
  7. 7.
    Lattanzi S, Cagnetti C, Foschi N, Lorusso A, Provinciali L, Silvestrini M. Eslicarbazepine acetate as adjunctive treatment in partial-onset epilepsy. Acta Neurol Scand. 2018;137:29–32.CrossRefGoogle Scholar
  8. 8.
    Lattanzi S, Cagnetti C, Matricardi S, Silvestrini M. Palliative non-resective surgery for drug-resistant epilepsy. Brain Dev. 2018;40:512–3.CrossRefGoogle Scholar
  9. 9.
    Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J, Hill C, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55:791–802.CrossRefGoogle Scholar
  10. 10.
    Ibeas Bih C, Chen T, Nunn AV, Bazelot M, Dallas M, Whalley BJ. Molecular targets of cannabidiol in neurological disorders. Neurotherapeutics. 2015;12:699–730.CrossRefGoogle Scholar
  11. 11.
    GW Pharmaceuticals plc and its U.S. subsidiary Greenwich Biosciences announce FDA approval of EPIDIOLEX® (cannabidiol) oral solution—the first plant-derived cannabinoid prescription medicine. Accessed Sep 2018.
  12. 12.
    Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.CrossRefGoogle Scholar
  13. 13.
    Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15:270–8.CrossRefGoogle Scholar
  14. 14.
    Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. Higgins JPT, Green S, editors. The Cochrane Collaboration, 2011. Accessed Jun 2018.
  15. 15.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.CrossRefGoogle Scholar
  16. 16.
    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.CrossRefGoogle Scholar
  17. 17.
    Lattanzi S, Cagnetti C, Foschi N, Provinciali L, Silvestrini M. Brivaracetam add-on for refractory focal epilepsy: a systematic review and meta-analysis. Neurology. 2016;86:1344–52.CrossRefGoogle Scholar
  18. 18.
    Lattanzi S, Brigo F, Grillo E, Cagnetti C, Verrotti A, Zaccara G, et al. Adjunctive eslicarbazepine acetate in pediatric patients with focal epilepsy: a systematic review and meta-analysis. CNS Drugs. 2018;32:189–96.CrossRefGoogle Scholar
  19. 19.
    Lattanzi S, Grillo E, Brigo F, Silvestrini M. Efficacy and safety of perampanel in Parkinson’s disease. A systematic review with meta-analysis. J Neurol. 2018;265:733–40.CrossRefGoogle Scholar
  20. 20.
    Lattanzi S, Cagnetti C, Danni M, Provinciali L, Silvestrini M. Oral and intravenous steroids for multiple sclerosis relapse: a systematic review and meta-analysis. J Neurol. 2017;264:1697–704.CrossRefGoogle Scholar
  21. 21.
    Lattanzi S, Brigo F, Cagnetti C, Di Napoli M, Silvestrini M. Patent foramen ovale and cryptogenic stroke or transient ischemic attack: to close or not to close? A systematic review and meta-analysis. Cerebrovasc Dis. 2018;45:193–203.CrossRefGoogle Scholar
  22. 22.
    Lattanzi S, Brigo F, Di Napoli M, Cagnetti C, Corradetti T, Silvestrini M. Endovascular treatment of symptomatic vertebral artery stenosis: a systematic review and meta-analysis. J Neurol Sci. 2018;391:48–53.CrossRefGoogle Scholar
  23. 23.
    Devinsky O, Patel AD, Thiele EA, Wong MH, Appleton R, Harden CL, et al.; GWPCARE1 Part A Study Group. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018;90:e1204–11.CrossRefGoogle Scholar
  24. 24.
    Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al.; Cannabidiol in Dravet Syndrome Study Group. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376:2011–2020.CrossRefGoogle Scholar
  25. 25.
    Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, et al.; GWPCARE3 Study Group. Effect of cannabidiol on drop seizures in the Lennox–Gastaut syndrome. N Engl J Med. 2018;378:1888-1897.CrossRefGoogle Scholar
  26. 26.
    Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, et al.; GWPCARE4 Study Group. Cannabidiol in patients with seizures associated with Lennox–Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391:1085–96.Google Scholar
  27. 27.
    Lattanzi S, Brigo F, Cagnetti C, Trinka E, Silvestrini M. Efficacy and safety of adjunctive cannabidiol in patients with Lennox–Gastaut syndrome: a systematic review and meta-analysis. CNS Drugs. (Epub 2018 Aug 21).CrossRefGoogle Scholar
  28. 28.
    Morrison G, Sardu M, Rasmussen C, Sommerville K, Roberts C, Blakey GE. Exposure-response analysis of cannabidiol oral solution for the treatment of Lennox–Gastaut syndrome [abstract no. 2.281]. The American Epilepsy Society Annual Meeting; 1–5 Dec 2017; Washington, DC. Accessed Jul 2018.
  29. 29.
    FDA. Cannabidiol oral solution. Full prescribing information. Accessed Jul 2018.
  30. 30.
    Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA; OV-1012 Study Investigators. Randomized, phase III study results of clobazam in Lennox–Gastaut syndrome. Neurology. 2011;77:1473–81.CrossRefGoogle Scholar
  31. 31.
    Glauser T, Kluger G, Sachdeo R, Krauss G, Perdomo C, Arroyo S. Rufinamide for generalized seizures associated with Lennox–Gastaut syndrome. Neurology. 2008;70:1950–8.CrossRefGoogle Scholar
  32. 32.
    Chiron C, Tonnelier S, Rey E, Brunet ML, Tran A, d’Athis P, et al. Stiripentol in childhood partial epilepsy: randomized placebo-controlled trial with enrichment and withdrawal design. J Child Neurol. 2006;21:496–502.CrossRefGoogle Scholar
  33. 33.
    FDA briefing document. Peripheral and central nervous system drugs. Advisory Committee Meeting. April 19, 2018. NDA 210365. Cannabidiol. Accessed Jul 2018.
  34. 34.
    US Department of Health and Human Services. Guidance for industry. Drug-induced liver injury: premarketing clinical evaluation. 2009. Accessed Jul 2018.
  35. 35.
    Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015;56:1246–51.CrossRefGoogle Scholar
  36. 36.
    Thiele EA, Devinsky O, Checketts D, Knappertz V. Cannabidiol (CBD) treatment responders analysis in patients with Lennox–Gastaut syndrome (LGS) on and off clobazam (CLB) [abstract no. 1.436]. The American Epilepsy Society Annual Meeting; 1–5 Dec 2017; Washington, DC. Accessed Jul 2018.
  37. 37.
    Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev. 2014;(3):CD009270.Google Scholar
  38. 38.
    Stockings E, Zagic D, Campbell G, Weier M, Hall WD, Nielsen S, et al. Evidence for cannabis and cannabinoids for epilepsy: a systematic review of con-trolled and observational evidence. J Neurol Neurosurg Psychiatry. 2018;89:741–53.CrossRefGoogle Scholar
  39. 39.
    Rhodes KM, Turner RM, Savović J, Jones HE, Mawdsley D, Higgins JPT. Between-trial heterogeneity in meta-analyses may be partially explained by reported design characteristics. J Clin Epidemiol. 2018;95:45–54.CrossRefGoogle Scholar
  40. 40.
    Devinsky O, Nabbout R, Miller I, Laux L, Zolnowska M, Wright S, et al. Maintenance of long-term safety and efficacy of cannabidiol (CBD) treatment in Dravet syndrome (DS): results of the open-label extension (OLE) trial (GWPCARE5) [abstract no. 1.289]. The American Epilepsy Society Annual Meeting; 1–5 Dec 2017; Washington, DC. Accessed Jul 2018.
  41. 41.
    Marsh ED, Mazurkiewicz-Beldzinska M, Halford JJ, Gunning B, Checketts D, Nichol K, et al. Maintained safety and efficacy of cannabidiol (CBD) in a long-term open-label trial in patients with Lennox–Gastaut syndrome (LGS) (GWPCARE 5) [abstract no. 2.271]. The American Epilepsy Society Annual Meeting; 1–5 Dec 2017; Washington, DC. Accessed Jul 2018.
  42. 42.
    Szaflarski JP, Bebin EM, Comi AM, Patel AD, Joshi C, Checketts D, et al.; CBD EAP study group. Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: expanded access program results. Epilepsia. 2018;59(8):1540–8. Scholar

via Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis | SpringerLink

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[WEB SITE] Investigating how epilepsy is triggered after a brain injury: Final Report

Posted Nov 1 2018 in News from Epilepsy Research UK

This is the final report for a 2015 project grant for £147,334 awarded to Professor Andy Trevelyan, Dr Ryley Parrish, Dr Claudia Racca, and Dr Simon Cockell at Newcastle University. 

In some cases of brain injury such as stroke, or brain trauma, people will go on to develop epilepsy. We know a little about how this happens – it can involve the death of brain cells and other rewiring of the circuits in the brain, as well as changes in which proteins are made by the brain cells, which in turn affects their function. However, we don’t understand how or why these changes happen, and more particularly how they might be prevented to stop epilepsy developing.

This project aimed to explore how a brain injury can lead to changes in how brain cells function. The research team discovered a notable feature of the rewiring, which is that one particular type of brain cell, the pyramidal cell, dictates what changes are made to the network.

High levels of pyramidal activity lead to a reduction in levels of a specific protein that is important for brain cell inhibition, whereas low levels of pyramidal activity cause the opposite change – an increase in these inhibitory proteins.

Professor Trevelyan and colleagues believe this may provide a means to understand the complexity of the brain changes that are associated with the development of epilepsy, and perhaps even a means to prevent it from happening.

Professor Trevelyan said: “This project has enabled us to further extend our understanding of the fundamental mechanisms by which seizures develop, and how the brain networks respond to these extreme periods of activity. We have uncovered important regulatory pathways which we hope will open up new avenues for treating the condition. On a personal level, the funding was also critical in allowing me to keep a key member of my research team, Dr Ryley Parrish. It is incredibly helpful for the research if we can maintain a research team together, because research is a slow process, and requires committed people who have been trained over many years. Only then can we start to make real inroads into understanding this difficult and complex condition.”


via Investigating how epilepsy is triggered after a brain injury: Final Report | Epilepsy Research UK

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[WEB SITE] New epilepsy warning device could save thousands of lives — ScienceDaily

Nightwatch bracelet on the arm of a young epilepsy patient.
Credit: LivAssured

A new high-tech bracelet, developed by scientists from the Netherlands detects 85 percent of all severe night-time epilepsy seizures. That is a much better score than any other technology currently available. The researchers involved think that this bracelet, called Nightwatch, can reduce the worldwide number of unexpected night-time fatalities in epilepsy patients. They published the results of a prospective trial in the scientific journal Neurology.

SUDEP, sudden unexpected death in epilepsy, is a major cause of mortality in epilepsy patients. People with an intellectual disability and severe therapy resistant epilepsy, may even have a 20% lifetime risk of dying from epilepsy. Although there are several techniques for monitoring patients at night, many attacks are still being missed.

Consortium researchers have therefore developed a bracelet that recognizes two essential characteristics of severe attacks: an abnormally fast heartbeat, and rhythmic jolting movements. In such cases, the bracelet will send a wireless alert to carers or nurses.

The research team prospectively tested the bracelet, known as Nightwatch, in 28 intellectually handicapped epilepsy patients over an average of 65 nights per patient. The bracelet was restricted to sounding an alarm in the event of a severe seizure. The patients were also filmed to check if there were any false alarms or attacks that the Nightwatch might have missed. This comparison shows that the bracelet detected 85 percent of all serious attacks and 96% of the most severe ones (tonic-clonic seizures), which is a particularly high score.

For the sake of comparison, the current detection standard, a bed sensor that reacts to vibrations due to rhythmic jerks, was tested at the same time. This signalled only 21% of serious attacks. On average, the bed sensor therefore remained unduly silent once every 4 nights per patient. The Nightwatch, on the other hand, only missed a serious attack per patient once every 25 nights on average. Furthermore, the patients did not experience much discomfort from the bracelet and the care staff were also positive about the use of the bracelet.

These results show that the bracelet works well, says neurologist and research leader Prof. Dr. Johan Arends. The Nightwatch can now be widely used among adults, both in institutions and at home. Arends expects that this may reduce the number of cases of SUDEP by two-thirds, although this also depends on how quickly and adequately care providers or informal carers respond to the alerts. If applied globally, it can save thousands of lives.

Watch the video here:

Story Source:

Materials provided by Eindhoven University of TechnologyNote: Content may be edited for style and length.

Journal Reference:

  1. Johan Arends, Roland D. Thijs, Thea Gutter, Constantin Ungureanu, Pierre Cluitmans, Johannes Van Dijk, Judith van Andel, Francis Tan, Al de Weerd, Ben Vledder, Wytske Hofstra, Richard Lazeron, Ghislaine van Thiel, Kit C.B. Roes, Frans Leijten. Multimodal nocturnal seizure detection in a residential care settingNeurology, 2018; 10.1212/WNL.0000000000006545 DOI: 10.1212/WNL.0000000000006545

via New epilepsy warning device could save thousands of lives — ScienceDaily

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[WEB SITE] What’s new and exciting in epilepsy research?

We asked Dr Robert Wykes, a translational medicine scientist for his personal perspective.  Here is his response:

Despite decades of new anti-epileptic drugs (AEDs) reaching market, the problem of drug refractory epilepsy remains. 25-30% of patients do not respond appropriately to AEDs. However in recent years advances in technology and non-pharmacological approaches are beginning to address this clinical need. We are beginning to see the translation of these therapies with exciting and promising results. I suspect within a decade, real progress will be made in treating or even curing the 25-30% who currently have few, often palliative options.

For some drug refractory patients surgery may be an option, but its success is dependent on precise localisation of a seizure onset zone. Improvements in neuroimaging and the electrophysiological devices used to detect seizure onset zones are increasing the accuracy of the area of the brain targeted for resection. There is also a realisation that many focal onset epilepsies may have a more distributed epileptic network. Mathematical modelling and application of advanced fMRI-EEG studies are identifying distributed epileptic networks. Further understanding of the importance of these networks may be key to improving surgical outcomes.

Surgery though is only an option for a minority of drug refractory patients. For those unsuitable for surgery promising and exciting results have been reported particularly in childhood epilepsies treated with cannabinoids (you can find out more about the ERUK position on medicinal cannabis here:) or components of the ketogenic diet such as decanoic acid. Further basic science investigations into the mechanism by which these compounds work may lead to molecules with improved anti-seizure properties. Antagomirs, molecules that block specific microRNAs upregulated in epileptic brain, have also shown considerable preclinical efficacy and are likely to enter clinical trials in the not too distant future.

Gene therapy holds promise, as this allows the ability to design strategies to achieve region-specific and cell-specific modification of neuronal and circuit excitability. The viral vectors that are used to deliver transgenes are increasingly reliable in terms of expressing the transgene, and data on long-term safety are accumulating from other neurological diseases. The potential to translate gene therapy research to human pharmacoresistant epilepsy is not straightforward. However a decade of preclinical proof or principle basic science has resulted in at least two gene therapy strategies currently being funded for first in human studies. It is envisioned that the first people to receive a gene therapy treatment for epilepsy could be within the next 18 months.

Recent advances in gene-editing technologies such as the CRISPR-Cas9 system could in the future result in entirely novel treatment for epilepsy by repairing disease-causing gene mutations. Although this technology offers the prospect of a ‘cure’ and can be applied to neurones in a petri dish, there are significant advances still required before this technology enters clinical translation for epilepsy.

I believe the biggest breakthrough will come however from basic science. It is astonishing to realize that we still don’t know how a seizure starts or how it stops! Recent advances that allow imaging of neuronal activity in awake rodents, coupled with the development of sophisticated multi-electrode devices and in combination with molecular techniques to target distinct types of neurons are shining a light on these fundamental questions. Further work in this area will result in a better understanding of seizure initiation and termination which may result in a radically different approach to treat people with epilepsy.

With many thanks to Dr Robert Wykes, University College London, Queen Square Institute of Neurology, for this contribution.

via What’s new and exciting in epilepsy research? | Epilepsy Research UK

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[WEB SITE] For patients with epilepsy has created a smart bracelet (VIDEO)

Для пациентов с эпилепсией создали «умный» браслет (ВИДЕО)

Dutch scientists have created the Nightwatch, a smart bracelet that monitors heart rate and movement of the user. In the case that the device will notice increased activity and reduction of muscles characteristic of epileptic seizure, the indicator light will turn red, and the bracelet itself will be able to report the attack to the medical staff.

This was reported in the journal Neurology.

The publication presents the results of the first study.

Repetitive seizures often occur when exposed to certain external and internal factors. For example, it is well known that the attack may be a touch to occur from exposure to bright flashing lights. In addition, epileptic seizures may accompany menstruation, as well as to synchronize with the cycles of sleep and wakefulness. In the latter case, the seizures often occur during sleep: to control them can be difficult, and to prevent the consequences without the use of special (often invasive) devices for monitoring — virtually impossible.

Especially to scientists from the University medical center Utrecht under the leadership of Johan Arends (Arends Johan) came up with a wearable bracelet, which is worn on the forearm of the patient and monitors two main indicators characteristic of epileptic seizures: elevated heart rate and irregular contraction of the muscles. Upon receipt of a signal from both of these indicators led color on the bracelet changes, but it also sends the audio signal to health workers.

The effectiveness of the bracelet tested on 28 patients with epilepsy: everyone wore the bracelet at least 65 nights. Scientists analyzed data about 1826 the night, which was 809 attacks. For additional control, participants were also videotaped during sleep, which allowed to calculate the percentage of false-positive and false-negative signals.

The bracelet has correctly recognized the attacks in 85 percent of cases, and about the most serious seizures, tonic-clonic, was able to report in 96 percent of cases.

Scientists hope that the use of the gadget will not only improve and simplify the monitoring of epileptic attacks, but also can reduce the number of sudden deaths due to epilepsy, which often occur with seizures during sleep. According to their estimates, the use of Nightwatch will reduce the number of deaths by two-thirds.

via For patients with epilepsy has created a smart bracelet (VIDEO) | The Siver Post

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[WEB SITE] New Epilepsy Bracelet Could Save Thousands of Lives

High-Tech “Nightwatch” is Capable of Detecting 85 Percent of Severe Night-Time Epileptic Seizures

Scientists in the Netherlands are optimistic that their new device will reduce the number of sudden unexpected death in epilepsy (SUDEP) patients worldwide. Currently, for people with an intellectual disability and severe treatment-resistant epilepsy, the outlook is poor, with a possible 20 percent lifetime risk of dying from epilepsy. While several techniques exist for monitoring patients at night, many seizures are still being missed.

With this in mind, a consortium of researchers (from Kempenhaeghe epilepsy centre, Eindhoven University of Technology, the Foundation for Epilepsy Institutions in the Netherlands (SEIN), UMC Utrecht, the Epilepsy Fund, patient representatives, and LivAssured) developed Nightwatch, a bracelet that recognizes unusually fast heartbeat and rhythmic jolting movements, two critical characteristics of severe attacks. When these occur, the device sends a wireless alert to caregivers or nurses.

In a test among 28 intellectually handicapped patients with epilepsy, over an average of 65 nights, Nightwatch detected 85 percent of all serious attacks and 96 percent of the most severe ones (tonic-clonic seizures). In comparison, a bed sensor, which is the current detection standard, sounded the alarm for only 21 percent of serious attacks. While the bed sensor was silent once every four nights per patient, the Nightwatch only missed a serious attack once every 25 nights, on average.

Prof. Dr. Johan Arends, neurologist and research leader, expects that the bracelet may reduce the number of SUDEP cases by two-thirds, although this also depends on the speed and efficiency with which caregivers respond to the alerts.

Source:, October 29, 2018


via New Epilepsy Bracelet Could Save Thousands of Lives | Managed Care magazine

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[WEB SITE] New method based on artificial intelligence may help predict epilepsy outcomes


Medical University of South Carolina (MUSC) neurologists have developed a new method based on artificial intelligence that may eventually help both patients and doctors weigh the pros and cons of using brain surgery to treat debilitating seizures caused by epilepsy. This study, which focused on mesial temporal lobe epilepsy (TLE), was published in the September 2018 issue of Epilepsia. Beyond the clinical implications of incorporating this analytical method into clinicians’ decision making processes, this work also highlights how artificial intelligence is driving change in the medical field.

Despite the increase in the number of epilepsy medications available, as many as one-third of patients are refractory, or non-responders, to the medication. Uncontrolled epilepsy has many dangers associated with seizures, including injury from falls, breathing problems, and even sudden death. Debilitating seizures from epilepsy also greatly reduce quality of life, as normal activities are impaired.

Epilepsy surgery is often recommended to patients who do not respond to medications. Many patients are hesitant to undergo brain surgery, in part, due to fear of operative risks and the fact that only about two-thirds of patients are seizure-free one year after surgery. To tackle this critical gap in the treatment of this epilepsy population, Dr. Leonardo Bonilha and his team in the Department of Neurology at MUSC looked to predict which patients are likely to have success in being seizure free after the surgery.

Neurology Department Chief Resident Dr. Gleichgerrcht explains that they tried “to incorporate advanced neuroimaging and computational techniques to anticipate surgical outcomes in treating seizures that occur with loss of consciousness in order to eventually enhance quality of life”. In order to do this, the team turned to a computational technique, called deep learning, due to the massive amount of data analysis required for this project.

The whole-brain connectome, the key component of this study, is a map of all physical connections in a person’s brain. The brain map is created by in-depth analysis of diffusion magnetic resonance imaging (dMRI), which patients receive as standard-of-care in the clinic. The brains of epilepsy patients were imaged by dMRI prior to having surgery.

Deep learning is a statistical computational approach, within the realm of artificial intelligence, where patterns in data are automatically learned. The physical connections in the brain are very individualized and thus it is challenging to find patterns across multiple patients. Fortunately, the deep learning method is able to isolate the patterns in a more statistically reliable method in order to provide a highly accurate prediction.

Currently, the decision to perform brain surgery on a refractory epilepsy patient is made based on a set of clinical variables including visual interpretation of radiologic studies. Unfortunately, the current classification model is 50 to 70 percent accurate in predicting patient outcomes post-surgery. The deep learning method that the MUSC neurologists developed was 79 to 88 percent accurate. This gives the doctors a more reliable tool for deciding whether the benefits of surgery outweigh the risks for the patient.

A further benefit of this new technique is that no extra diagnostic tests are required for the patients, since dMRIs are routinely performed with epilepsy patients at most centers.

This first study was retrospective in nature, meaning that the clinicians looked at past data. The researchers propose that an ideal next step would include a multi-site prospective study. In a prospective study, they would analyze the dMRI scans of patients prior to surgery and follow-up with the patients for at least one year after surgery. The MUSC neurologists also believe that integrating the brain’s functional connectome, which is a map of simultaneously occurring neural activity across different brain regions, could enhance the prediction of outcomes.

Dr. Gleichgerrcht says that the novelty in the development of this study lies in the fact that this “is not a question of human versus machine, as is often the fear when we hear about artificial intelligence. In this case, we are using artificial intelligence as an extra tool to eventually make better informed decisions regarding a surgical intervention that holds the hope for a cure of epilepsy in a large number of patients.”


via New method based on artificial intelligence may help predict epilepsy outcomes

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