Treatment of myoclonic seizures in patients with juvenile myoclonic epilepsy

Drug treatment of Juvenile myoclonic epilepsy (JME) is mainly based on clinical experience and prospective and retrospective studies, with little evidence from randomized clinical trials. There are no head-to-head comparisons between old and new antiepileptic drugs (AEDs) and no drugs licensed specifically for JME. Valproate is unquestionably the drug of the first choice in men with JME. In women, lamotrigine should be preferred regarding teratogenicity and side effects of valproate. In addition, levetiracetam and topiramate are effective and can be use in combination or as second line treatment. Some AEDs can aggravate JME. In addition of AEDs, non-pharmacological treatments are important in JME. JME usually require lifelong treatment because seizures nearly always return after withdrawal of therapy

The classification of chronic daily headache in French children and adolescents: A comparison between the second edition of the International Classification of Headache Disorders and Silberstein-Lipton criteria

Few data are available on the applicability of both the criteria proposed by Silberstein and Lipton (S-L) and the International Classification of Headache Disorders-II (ICHD-II) in the classification of children and adolescents with chronic daily headache (CDH). The International Headache Society recently added revised criteria (ICHD-IIR) for chronic migraine to its Appendix. We retrospectively reviewed all charts of 34 children and adolescents (<17 years) with primary CDH presenting to the outpatient clinic of the Universitary Department of Neuropediatrics of Lille between February 2004 and February 2006 and tried to classify their CDH according to both S-L criteria and the recently published ICHD-IIR. Thirty-two children (94%) and 33 children (97%) could respectively be successfully classified into one subtype of CDH according to the S-L classification and the ICHD-IIR. Transformed migraine was the most common diagnosis (61.8%), followed by new daily-persistent headache (20.6%) when the S-L criteria were used. Twenty-three children and adolescents (67.6%) could be classified under one of the migraine categories according to the ICHD-IIR classification. We think that both S-L and ICHD-II classifications, when used with detailed headache histories and diaries, are adequate to classify chronic daily headache in children and adolescents

Expert Opinion On The Management Of Lennox-gastaut Syndrome: Treatment Algorithms And Practical Consideration

Lennox-Gastaut syndrome (LGS) is a severe epileptic and developmental encephalopathy that is associated with a high rate of morbidity and mortality. It is characterized by multiple seizure types, abnormal electroencephalographic features, and intellectual disability. Although intellectual disability and associated behavioral problems are characteristic of LGS, they are not necessarily present at its outset and are therefore not part of its diagnostic criteria. LGS is typically treated with a variety of pharmacological and non-pharmacological therapies, often in combination. Management and treatment decisions can be challenging, due to the multiple seizure types and comorbidities associated with the condition. A panel of five epileptologists met to discuss consensus recommendations for LGS management, based on the latest available evidence from literature review and clinical experience. Treatment algorithms were formulated. Current evidence favors the continued use of sodium valproate (VPA) as the first-line treatment for patients with newly diagnosed de novo LGS. If VPA is ineffective alone, evidence supports lamotrigine, or subsequently rufinamide, as adjunctive therapy. If seizure control remains inadequate, the choice of next adjunctive antiepileptic drug (AED) should be discussed with the patient/parent/caregiver/clinical team, as current evidence is limited. Non-pharmacological therapies, including resective surgery, the ketogenic diet, vagus nerve stimulation, and callosotomy, should be considered for use alongside AED therapy from the outset of treatment. For patients with LGS that has evolved from another type of epilepsy who are already being treated with an AED other than VPA, VPA therapy should be considered if not trialed previously. Thereafter, the approach for a de novo patient should be followed. Where possible, no more than two AEDs should be used concomitantly. Patients with established LGS should undergo review by a neurologist specialized in epilepsy on at least an annual basis, including a thorough reassessment of their diagnosis and treatment plan. Clinicians should always be vigilant to the possibility of treatable etiologies and alert to the possibility that a patient's diagnosis may change, since the seizure types and electroencephalographic features that characterize LGS evolve over time. To date, available treatments are unlikely to lead to seizure remission in the majority of patients and therefore the primary focus of treatment should always be optimization of learning, behavioral management, and overall quality of life

Altered vaccine-induced immunity in children with Dravet syndrome

International audienceDravet syndrome (DS) is a refractory epileptic syndrome. Vaccination is the trigger of the first seizure in about 50% of cases. Fever remains a trigger of seizures during the course of the disease. We compared ex vivo cytokine responses to a combined aluminium-adjuvanted vaccine of children with DS to sex-and age-matched heathy children. Using ex vivo cytokine responses of peripheral-blood mononuclear cells and monocytes, we found that vaccine responsiveness is biased toward a proinflammatory profile in DS with a M1 phenotype of monocytes. We provide new insight into immune mechanisms associated with DS that might guide research for the development of new immunotherapeutic agents in this epilepsy syndrome

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study

IntroductionThe PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date.MethodsThis post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs.ResultsThe Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p &lt; 0.001), focal seizures (65.0% vs. 36.8%; p &lt; 0.001) and GTCS (83.7% vs. 67.2%; p &lt; 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p &lt; 0.001]; focal seizures, 29.4% vs. 8.7% [p &lt; 0.001]; GTCS, 69.0% vs. 48.1% [p &lt; 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p &lt; 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031).DiscussionThis study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures

Epilepsy research in Africa: A scoping review by the ILAE Pediatric Commission Research Advocacy Task Force

Objective: Despite the high prevalence of epilepsy in Africa, evaluation of epi- lepsy research trends on the continent is lacking. Without establishing effective research, improvement in care for people with epilepsy cannot be effectively strategized or targeted. Methods: A scoping review of the peer-reviewed literature on epilepsy from Africa (1989–2019) was conducted. The aim was to understand from this what areas are well researched versus underresearched based on published epilepsy topics. Results: A total of 1227 publications were identified and assessed. A significant increase in publications occurred over the 30 years assessed. African author lead- ership was evident in most reports. Nine countries had \u3e50 publications identi- fied; the remaining 45 countries had \u3c50 or no publications. Research studies were typically of lower quality (case series and observational studies). Research themes were more focused on clinical epilepsy (descriptive observational studies) and social aspects (qualitative surveys). However, there were a number of unique and strong themes, specifically for neurocysticercosis and nodding syndrome, where strong research collaborations were evident, basic science understandings were explored, and interventional models were established. Significance: Despite Africa being the continent with the most countries, it is lacking in the quantity, quality, and for some areas, relevance of research on epilepsy. Targeted approaches are needed to upskill the strength of research un- dertaken with more basic science, interventional, and randomized controlled studies. Themes of research need to promote those with unique African content but also to align with current international research areas that have impact on care delivery, such as epilepsy surgery and epilepsy genetics. For this to be possi- ble, it is important to strengthen research hubs with collaborations that empower Africa to own its epilepsy research journey

Retrospective chart review study of use of cannabidiol (CBD) independent of concomitant clobazam use in patients with Lennox-Gastaut syndrome or Dravet syndrome

PURPOSE: This retrospective chart review study (GWEP20052) evaluated plant-derived highly purified cannabidiol (CBD; Epidyolex®; 100 mg/mL oral solution) use without clobazam as add-on therapy in patients aged ≥2 years with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) enrolled in a European Early Access Program. METHODS: Data were extracted from patient charts covering a period starting 3 months before CBD treatment and concluding after 12 months of CBD treatment, or sooner if a patient discontinued CBD or started clobazam. RESULTS: Of 114 enrolled patients, data were available for 107 (92 LGS, 15 DS) who received CBD without clobazam for ≥3 months. Mean age: 14.5 (LGS) and 10.5 (DS) years; female: 44% (LGS) and 67% (DS). Mean time-averaged CBD dose: 13.54 (LGS) and 11.56 (DS) mg/kg/day. Median change from baseline in seizure frequency per 28 days over 3-month intervals varied from -6.2% to -20.9% for LGS and 0% to -16.7% for DS. Achievement of ≥50% reduction in drop (LGS) or convulsive (DS) seizures at 3 and 12 months: LGS, 19% (n = 69) and 30% (n = 53); DS, 21% (n = 14) and 13% (n = 8). Retention on CBD without clobazam (enrolled set): 94%, 80%, 69%, and 63% at 3, 6, 9, and 12 months. Adverse event (AE) incidence was 31%, most commonly somnolence, seizure, diarrhea, and decreased appetite. Two patients discontinued CBD owing to AEs, and four patients with LGS experienced elevated liver enzymes. CONCLUSION: Results support favorable effectiveness and retention of CBD without concomitant clobazam for up to 12 months in clinical practice

Medical treatment in infants and young children with epilepsy: Off-label use of antiseizure medications Survey Report of ILAE Task Force Medical Therapies in Children

OBJECTIVE: Antiseizure medications (ASMs) remain the mainstay of epilepsy treatment. These ASMs have mainly been tested in trials in adults with epilepsy, which subsequently led to the market authorization (MA). For treatment of -especially young- children with epilepsy, several ASMs do not have a MA and guidelines are lacking, subsequently leading to "off-label" use of ASMs. Even though "off-label" ASM prescriptions for children could lead to more adverse events, it can be clinically appropriate and rational if the benefits outweigh the risks. This could be the case if "on-label" ASM, in mono- or polytherapy, fail to achieve adequate seizure control. METHODS: The Medical Therapies Task Force of the International League Against Epilepsy (ILAE) Commission for Pediatrics performed a survey to study the current treatment practices in six classic, early life epilepsy scenarios. Our aim was not only to study first- and second-line treatment preferences, but also to illustrate the use of "off-label" drugs in childhood epilepsies. RESULTS: Our results reveal that several ASMs (e.g. topiramate, oxcarbazepine, benzodiazepines) are prescribed "off-label" in distinct scenarios of young children with epilepsy. In addition, recent scientific guidelines were not always adopted by several survey respondents, suggesting a potential knowledge gap. SIGNIFICANCE: We report the relatively common use of "off-label" prescriptions that underlines the need for targeted and appropriately designed clinical trials, including younger patients, which will also result in the ability to generate evidence-based guidelines

Guidance on Dravet syndrome from infant to adult care: road map for treatment planning in Europe

Dravet syndrome (DS) is a severe, rare, and complex developmental and epileptic encephalopathy affecting 1 in 16 000 live births and characterized by a drug-resistant epilepsy, cognitive, psychomotor, and language impairment, and behavioral disorders. Evidence suggests that optimal treatment of seizures in DS may improve outcomes, even though neurodevelopmental impairments are the likely result of both the underlying genetic variant and the epilepsy. We present an updated guideline for DS diagnosis and treatment, taking into consideration care of the adult patient and nonpharmaceutical therapeutic options for this disease. This up-to-date guideline, which is based on an extensive review of the literature and culminates with a new treatment algorithm for DS, is a European consensus developed through a survey involving 29 European clinical experts in DS. This guideline will serve professionals in their clinical practice and, as a consequence, will benefit DS patients and their families

L'anxiété et les symptômes dépressifs chez les parents d'enfants atteints de syndrome de Dravet

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