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We describe real-world experience with cannabidiol (CBD) in adults with Dravet Syndrome (DS) via GW Pharma early access programme at two UK neurology centres. Adults with genetically-confirmed DS had CBD added to existing therapy, titrated up to 20 mg/kg, as tolerated. The primary outcome measure was percentage reduction in convulsive seizures. Secondary outcome measures included changes in myoclonic seizures, and in cognition and quality of life as assessed by the Caregiver Global Impression of Change (CGIC), and incidence of adverse events (AEs). 18 adults (7 female; median age 27.5 years; range 20–51) were included. Median follow-up was 176 days. In one, another antiseizure drug, clobazam, was introduced during the programme. 3/17 (17.6%) had >30% reduction in convulsive seizures (range: 87.5–100%). AEs occurred in all, the most common being transaminitis (52.9%). Behavioural AEs led to discontinuation in 3/18 (16.7%), including a seizure-free responder. In 7/18, CBD was stopped due to lack of effect. 8/18 continue on treatment. Improvements in CGIC were reported in 41.2% and 47.1% by physicians and families, respectively. 17.6% achieved sufficient reduction in convulsive seizure frequency to qualify for NHS funding. AEs led to withdrawal in only 16.7%. Close monitoring and dose adjustments of other antiseizure drugs were necessary.

New-onset refractory status epilepticus and its subcategory febrile infection-related epilepsy syndrome are rare devastating clinical presentations in those without pre-existing relevant history, often in schoolchildren or young adults, without a clear cause on initial investigations. A cause is later identified in up to half of adults, but in many fewer children. Patients often require protracted intensive care and are at significant risk of dying. Functional disability is common and subsequent chronic epilepsy is the norm, but some people do have good outcomes, even after prolonged status epilepticus. Patients need prompt investigations and treatment. Anaesthetic and antiseizure medications are supplemented by other treatment modalities, including the ketogenic diet. Despite limited evidence, it is appropriate to try to modify the presumed underlying pathogenesis with immune modulation early, with a more recent focus on using interleukin inhibitors. Optimising management will require concerted multicentre international efforts.

Dementia is associated with an increased risk of unprovoked seizures and epilepsy, which carry a risk of reduced quality of life and adverse events. The management of seizures and epilepsy in patients with cognitive impairment presents a multitude of challenges for the clinician. The pathology underlying the dementia syndrome may differ and range from neurodegeneration associated with accumulation of beta-amyloid and tau to ischaemic changes, and hence a seizure in a patient with dementia may be considered having a structural cause. Nevertheless, taking the decision to treat or not to treat seizures in dementia patients can be difficult, as the risks of recurrent seizures versus an increased risk of adverse effects of antiepileptic medications have to be weighed up against each other. Moreover, seizures, especially focal onset impaired awareness seizures (previously called complex partial seizures) may be difficult to identify for both patients and caregivers. This may be partly due to lack of awareness of seizures, lack of insight by the patient, and in some instances, such as Lewy body dementia, similarities with other non-epileptic phenomena that are part of the disease. Enquiring about seizure markers should be part of the routine follow-up of patients with dementia and carers should be taught to identify and record episodes of altered awareness. This chapter will present a background on the pathophysiology of seizures and epilepsy in dementia, a guide to diagnosis and differential diagnosis, provide a summary of treatment options, and a discussion on practical issues to consider when choosing an antiepileptic drug, including side effects. These topics will be supplemented by three case scenarios exemplifying these issues.

We present a case of non-convulsive status epilepticus in a 57-year-old woman with a schizoaffective disorder, without an antecedent seizure history, with two possible aetiologies including SARS-CoV-2 infection and clozapine uptitration. We discuss the presentation, investigations, differential diagnosis and management. In particular, we focus on the electroencephalogram (EEG) findings seen in this case and the electroclinical response to antiepileptic medication. We review the literature and discuss the relevance of this case to the SARS-CoV-2 global pandemic. We emphasise the importance of considering possible neurological manifestations of SARS-CoV-2 infection and highlight seizure disorder as one of the possible presentations. In addition, we discuss the possible effects of clozapine on the electroclinical presentation by way of possible seizure induction as well as discuss the possible EEG changes and we highlight that this needs to be kept in mind especially during rapid titration.

Background: The ability to manipulate the activity of interneurons with optogenetic tools offers the possibility of interfering with diseases caused by altered neuronal inhibition and synchrony, including epilepsy and schizophrenia. To develop vectors for therapeutic approaches, targeting optogenetic constructs to interneurons is therefore a key requirement. We investigated whether the interneuron‐specific promoters glutamic acid decarboxylase (GAD)67 and cholecystokinin (CCK) allowed targeted lentiviral delivery of opsins to interneurons as a whole, or specifically CCK+ interneurons. Methods: We generated lentiviral (LV) plasmids encoding channelrhodopsin (ChR2) and halorhodopsin (NpHR) tagged with fluorophores and driven by GAD67 or CCK promoters. Adeno‐associated virus (AAV) and LV vectors carrying opsins driven by pyramidal cell promoters were used as controls. We transduced neuronal cultures and rodent brain in vivo, immunostained specimens 6–8 weeks after in vivo injection and 7–14 days after in vitro transduction, and evaluated volume and specificity of expression by confocal microscopy. Results: In vitro, 90% (19/21) of LV‐CCK‐NpHR2.0‐EYFP expressing neurons were CCK+. In vivo, LV‐GAD67‐ChR2‐mCherry was expressed in 2.6% (5/193), LV‐GAD67‐NpHR2.0‐EYFP in approximately 15% (43/279) and LV‐CCK‐NpHR2.0‐EYFP in 47% (9/19) of hippocampal GABA+ interneurons. GAD67 vectors expressed in larger volumes than CCK‐driven constructs. AAV vector controls achieved the largest expression volumes. Conclusions: LV‐CCK‐NpHR2.0‐EYFP may be useful for targeting CCK+ interneurons in culture. GAD67/CCK‐driven lentiviral constructs are expressed in vivo, although expression is not specific for interneurons. Overall, expression levels are low compared to opsins driven by pyramidal cell promoters. A better understanding of GAD67 and CCK promoter structure or alternative techniques is required to reliably target opsins to interneurons using viral vectors.

Optogenetics is a novel technology that combines optics and genetics by optical control of microbial opsins, targeted to living cell membranes. The versatility and the electrophysiologic characteristics of the light-sensitive ion-channels channelrhodopsin-2 (ChR2), halorhodopsin (NpHR), and the light-sensitive proton pump archaerhodopsin-3 (Arch) make these optogenetic tools potent candidates in controlling neuronal firing in models of epilepsy and in providing insights into the physiology and pathology of neuronal network organization and synchronization. Opsins allow selective activation of excitatory neurons and inhibitory interneurons, or subclasses of interneurons, to study their activity patterns in distinct brain-states in vivo and to dissect their role in generation of synchrony and seizures. The influence of gliotransmission on epileptic network function is another topic of great interest that can be further explored by using light-activated Gq protein-coupled opsins for selective activation of astrocytes. The ever-growing optogenetic toolbox can also be combined with emerging techniques that have greatly expanded our ability to record specific subtypes of cortical and hippocampal neurons in awake behaving animals such as juxtacellular recording and two-photon guided whole-cell recording, to identify the specific subtypes of neurons that are altered in epileptic networks. Finally, optogenetic tools allow rapid and reversible suppression of epileptic electroencephalography (EEG) activity upon photoactivation. This review outlines the most recent advances achieved with optogenetic techniques in the field of epilepsy by summarizing the presentations contributed to the 13th ILAE WONOEP meeting held in the Laurentian Mountains, Quebec, in June 2013.

Nested between Venezuela in the west, Brazil in the south and Suriname in the east, Guyana lies on the northern Atlantic coast of the South American continent, just a few degrees above the equator line (figure 1). With a size of 214 970 km2 (comparable with the area of the UK) but a population of only about 735 554, it is one of the least densely populated countries in the world. Most of the population resides on the fertile coastal plains along Guyana's Atlantic shore, while 90% of the country is covered in lush and almost inaccessible tropical rainforest. While still part of the South American continent, Guyanese culture and economy is orientated towards the Caribbean, and with a population of East-Indian, African and Amerindian descent, Guyana is a vibrant melting pot for different cultures. Figure 1 Geography of Guyana. (A) Geographical map of Guyana and (B) its location on the South American continent. (C) The national flag, (D) the national bird, the Hoatzin or Canje Pheasant, captured on camera during a boating trip along the Essequibo River. (E) The beautiful Rupununi Savannah located in the country’s southwest, bordering the Brazilian Amazon. Maps are under Gnu public licence. Figure 1A was modified from the original (Vardion, Image A, Wikipaedia) and is under Creative Commons CC0 1.0 Universal Public Domain Dedication. Figure 1B was modified from the original (Urutseg, Wikipaedia) and is under Multi-license with GFDL and Creative Commons CC-BY-SA-2.5 and older versions (2.0 and 1.0). At the end of a post-CCT (UK Certificate of Completion of Training) fellowship in epilepsy in October 2015, LMR was hosted by JC at the Department of Medicine, Georgetown Public Hospital, as part of the multidisciplinary Epilepsy Education Project invited by the Epilepsy Foundation for Guyana. Approaching the capital Georgetown by air, the origin of the ancient Amerindian name …

International audience; Introduction: The aim of the study was the evaluation of the added value of depth to subdural electrodes in delineating epileptogenicity of focal cortical dysplasias (FCDs) and to test the Epileptogenicity Index (EI) in this setting. Material and methods: Fifteen patients with FCD underwent iEEG with subdural and depth electrodes. Visual/EI analysis was performed in up to three habitual seizures per patient. Results: Visual analysis: Grid onset seizures (n=10) started in electrodes overlying the lesion in 7 and remote from it in 3 cases. Depth onset seizures (n=7) affected only intralesional contacts in 4, intra-and extralesional in 2, and exclusively extralesional in 1 patient. Seizures started in depth and grid contacts simultaneously in 2 cases. EI analysis: The EI completely confirmed visual localization of seizure onset in 8 cases and depicted ictal onset-time accurately in 13. Beta/gamma ictal patterns were most reliably captured. Impact on surgical decision: Resection outline differed from MRI lesion in 7 patients based on grid and in three based on depth electrode information. Discussion: In FCD, seizures can be generated within gyral/deep tissue appearing normal on imaging. Conclusion: Investigating FCD with subdural and depth electrodes is efficient to outline the seizure onset zone. The EI is a helpful additional tool to quantify epileptogenicity. Specific ictal patterns are prerequisite for reliable results. (C) 2016 Elsevier Inc. All rights reserved.

The ability to manipulate the activity of interneurons with optogenetic tools offers the possibility of interfering with diseases caused by altered neuronal inhibition and synchrony, including epilepsy and schizophrenia. To develop vectors for therapeutic approaches, targeting optogenetic constructs to interneurons is therefore a key requirement. We investigated whether the interneuron-specific promoters glutamic acid decarboxylase (GAD)67 and cholecystokinin (CCK) allowed targeted lentiviral delivery of opsins to interneurons as a whole, or specifically CCK+ interneurons.We generated lentiviral (LV) plasmids encoding channelrhodopsin (ChR2) and halorhodopsin (NpHR) tagged with fluorophores and driven by GAD67 or CCK promoters. Adeno-associated virus (AAV) and LV vectors carrying opsins driven by pyramidal cell promoters were used as controls. We transduced neuronal cultures and rodent brain in vivo, immunostained specimens 6-8 weeks after in vivo injection and 7-14 days after in vitro transduction, and evaluated volume and specificity of expression by confocal microscopy.In vitro, 90% (19/21) of LV-CCK-NpHR2.0-EYFP expressing neurons were CCK+. In vivo, LV-GAD67-ChR2-mCherry was expressed in 2.6% (5/193), LV-GAD67-NpHR2.0-EYFP in approximately 15% (43/279) and LV-CCK-NpHR2.0-EYFP in 47% (9/19) of hippocampal GABA+ interneurons. GAD67 vectors expressed in larger volumes than CCK-driven constructs. AAV vector controls achieved the largest expression volumes.LV-CCK-NpHR2.0-EYFP may be useful for targeting CCK+ interneurons in culture. GAD67/CCK-driven lentiviral constructs are expressed in vivo, although expression is not specific for interneurons. Overall, expression levels are low compared to opsins driven by pyramidal cell promoters. A better understanding of GAD67 and CCK promoter structure or alternative techniques is required to reliably target opsins to interneurons using viral vectors.

A 50-year-old right-handed retired family business manager developed progressive left-sided weakness over 5 days after a mechanical fall. She remembered catching her foot on the carpet and falling down a flight of stairs, followed by severe neck pain over C4-C5 and inability to get up for nearly an hour. Over the subsequent month her symptoms progressed and she presented to the hospital with an asymmetric spastic paraparesis, loss of pinprick sensation in her arms and legs, loss of vibration sense to both hips, and double incontinence.