BACKGROUND: When use of a single antiseizure medication (ASM) fails to induce seizure remission, add-on therapy is justified. Perampanel (PER) is approved in Europe as adjunctive therapy for focal, focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures. Aim of the study was to establish whether PER is suitable for first add-on use.
METHODS: A Delphi methodology was adopted to assess consensus on a list of 39 statements produced by an Expert Board of 5 epileptologists. Using an iterative process, statements were finalized by a Delphi Panel of 84 Italian pediatric and adult neurologists. Each statement was rated anonymously to determine level of agreement on a 9-point Likert scale. Consensus was established as agreement by at least 80% of the panelists. The relevance of each statement was also assessed on a 3-point scale.
RESULTS: Consensus was achieved for 37 statements. Characteristics of PER considered to justify its use as first add-on include evidence of a positive impact on quality of life based on long term retention data, efficacy, tolerability, and ease of use; no worsening of cognitive functions and sleep quality; a low potential for drug interactions; a unique mechanism of action. Potential unfavorable factors are the need for a relatively slow dose titration; the potential occurrence of behavioral adverse effects; lack of information on safety when used in pregnancy; limited access to plasma PER levels.
CONCLUSIONS: Perampanel has many features which justify its use as a first add-on. Choice of an ASM as first add-on should be tailored to individual characteristics.

When monotherapy used alone or sequentially fails to achieve seizure control, a trial of combination therapy may be considered.
To define optimal criteria to guide choice of an antiseizure medication (ASM) for use as first add-on.
A standardized Delphi procedure was applied to produce a list of consensus statements. First, an Expert Board consisting of 5 epileptologists agreed on a set of 46 statements relevant to the objective. The statements were then finalized through an iterative process by a Delphi Panel of 84 Italian pediatric and adult neurologists with expertise in the management of epilepsy. Panel members provided anonymous ratings of their level of agreement with each statement on a 9-point Likert scale.
Consensus, defined as agreement by at least 80% of Panel members, was reached for 36 statements. Medication-related factors considered to be important for drug selection included efficacy, tolerability and safety, interaction potential, mechanism of action, and ease of use. The need to optimize adherence and to tailor drug selection to individual characteristics was emphasized.
Choice of an ASM for first add-on requires consideration of many factors, many of which also apply to choose initial treatment. Factors more specifically relevant to add-on use include drug interaction potential and the preference for an ASM with a different mechanism of action.

Following publication in 2014 of the International League Against Epilepsy (ILAE) official report changing the definition of epilepsy, a number of questions remain unresolved in regard to deciding when to start treatment and to the choice of a particular antiseizure medication (ASM). This study uses a Delphi method to update consensus among a panel of experts on the initiation of epilepsy treatment in order to provide insight regarding those questions. The study was undertaken in four phases. Firstly, a multi-center steering committee met to review relevant bibliography and to draft a questionnaire. Secondly, a panel of neurologists specialized in epilepsy was selected and convened. Thirdly, an online survey was carried out in two rounds. Fourthly, the final results were discussed at a face-to-face meeting of the steering committee to draw conclusions. The final questionnaire focused on three independent sections: the decision to commence ASM in different clinical situations, the choice of initial monotherapy depending on the type of epilepsy and the patient\'s age/sex (including childbearing potential), and the choice of initial monotherapy depending on comorbidity. In these two latter sections, fourteen ASMs approved for monotherapy use by the EMA and available in Spain were considered. Regarding the decision as to when to commence treatment, the results show agreement exists to initiate treatment following a first generalized tonic-clonic seizure or a focal seizure if the electroencephalography (EEG) reveals epileptiform activity, if the MRI reveals a lesion, or when it occurs in elderly patients. With respect to the choice of initial monotherapy depending on the type of epilepsy and the patient\'s age/sex profile, it is agreed to avoid valproic acid (VPA) in women with childbearing potential, with levetiracetam (LEV) and lamotrigine (LTG) being the preferable options in generalized epilepsy. In focal epilepsy, the options are broader, particularly in men, and include the most recent ASMs approved for monotherapy. In the elderly, LEV, lacosamide (LCM), eslicarbazepine acetate (ESL) and LTG are considered the most suitable drugs for initiating treatment. With regard to comorbidities, the recommendation is to avoid enzyme inducing ASMs, with LEV, the most recent ASMs approved for monotherapy and LTG being the preferred options. In conclusion, as the ILAE definition states, there are different situations that lead to treatment initiation after a first seizure. When choosing the first ASM, the type of epilepsy, childbearing potential and drug-drug interaction are key factors.

UNASSIGNED: Certain HLA variants are associated with an increased risk of hypersensitivity reactions to specific drugs. Both the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) have issued actionable HLA gene - drug interaction guidelines but diagnostic test criteria remain largely unknown. We present an overview of the diagnostic test criteria of the actionable HLA - drug pairs.
UNASSIGNED: A systematic literature search was conducted in PubMed, Embase, Web of Science and Cochrane Library. Original case-control and cohort studies were selected and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and number needed to genotype (NNG) were calculated for the actionable HLA-drug pairs.
UNASSIGNED: In general, the HLA tests show high specificity and NPV for predicting hypersensitivity reactions. The sensitivity of HLA tests shows a wide range, from 0-33% for HLA-B*1502 testing to predict lamotrigine induced SJS/TEN up to 100% for HLA-B*5701 to predict immunologically confirmed abacavir hypersensitivity syndrome (ABC-HSR). PPV is low for all tests except for HLA-B*5701 and ABC-HSR which is approximately 50%. HLA-B*5701 to predict ABC-HSR shows the lowest NNG followed by HLA-B*5801 for allopurinol induced severe cutaneous adverse drug reactions and HLA-B*1502 for carbamazepine induced SJS/TEN.
UNASSIGNED: This is the first overview of diagnostic test criteria for actionable HLA-drug pairs. Studies researching HLA genes and hypersensitivity are scarce for some of the HLA-drug pairs in some populations and patient numbers in studies are small. Therefore, more research is necessary to calculate the diagnostic test criteria more accurately.

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BACKGROUND: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO) conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors. As part I of the survey, the aim of this study is to evaluate national patterns of clinical practice about antiepileptic drug (AED) and steroid usage for management of brain tumors.
METHODS: A web-based survey was sent to all members of the KSNO by email. The survey included 9 questions of AED usage and 5 questions of steroid usage for brain tumor patients. All questions were developed by consensus of the Guideline Working Group.
RESULTS: The overall response rate was 12.8% (54/423). Regarding AED usage, the majority of respondents (95.2%) routinely prescribed prophylactic AEDs for patients with seizure at the peri/postoperative period. However, as many as 72.8% of respondents prescribed AED routinely for seizure-naïve patients, and others prescribed AED as the case may be. The duration of AED prophylaxis showed wide variance according to the epilepsy status and the location of tumor. Levetiracetam (82.9%) was the most preferred AED for epilepsy prophylaxis. Regarding steroid usage, 90.5% of respondents use steroids in perioperative period, including 34.2% of them as a routine manner. Presence of peritumoral edema (90.9%) was considered as the most important factor determining steroid usage followed by degree of clinical symptoms (60.6%). More than half of respondents (51.2%) replied to discontinue the steroids within a week after surgery if there are no specific medical conditions, while 7.3% preferred slow tapering up to a month after surgery.
CONCLUSIONS: The survey demonstrated the prevailing practice patterns on AED and steroid usage in neuro-oncologic field among members of the KSNO. This information provides a point of reference for establishing a practical guideline in the management of brain tumor patients.

Background: Focal-onset seizures and encephalopathy are prominent features of a stroke-like episode, which is a severe neurological manifestation associated with subtypes of mitochondrial disease. Despite more than 30 years of research, the acute treatment of stroke-like episodes remains controversial. Methods: We used the modified Delphi process to harness the clinical expertise of a group of mitochondrial disease specialists from five European countries to produce consensus guidance for the acute management of stroke-like episodes and commonly associated complications. Results: Consensus on a new definition of mitochondrial stroke-like episodes was achieved and enabled the group to develop diagnostic criteria based on clinical features, neuroimaging and/or electroencephalogram findings. Guidelines for the management of strokelike episodes were agreed with aggressive seizure management strongly recommended at the outset of stroke-like episodes. Conclusions: Our consensus statement defines stroke-like episodes in terms of an epileptic encephalopathy and we have used this to revise both diagnostic criteria and guidelines for management. A prospective, multi-centre, randomised controlled trial is required for evaluating the efficacy of any compound on modifying the trajectory of stroke-like episodes.

Adults with solid brain metastases who have not experienced a seizure.
Do prophylactic antiepileptic drugs (AEDs) decrease the risk of seizures in nonsurgical patients with brain metastases who are otherwise seizure-free?
Level 3: Prophylactic AEDs are not recommended for patients with brain metastases who did not undergo surgical resection and are otherwise seizure-free.
Do prophylactic AEDs decrease the risk of seizures in patients with brain metastases and no prior history of seizures in the postoperative setting?
Level 3: Routine postcraniotomy AED use for seizure-free patients with brain metastases is not recommended.The full guideline can be found at: https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_8.

The aim of this study was to develop and achieve consensus on a core list of important knowledge items that community pharmacists should know on women\'s issues in epilepsy.
This was a consensual study using a modified Delphi technique. Knowledge items were collected from the literature and from nine key contacts who were interviewed on their views on what information community pharmacists should have on women\'s issues in epilepsy. More knowledge items were suggested by five researchers with interest in women\'s issues who were contacted to rate and comment on the knowledge items collected. Two iterative Delphi rounds were conducted among a panel of pharmacists (n=30) to achieve consensus on the knowledge items to be included in the core list. Ten panelists ranked the knowledge items by their importance using the Analytical Hierarchy Process (AHP).
Consensus was achieved to include 68 knowledge under 13 categories in the final core list. Items ranked by their importance were related to the following: teratogenicity (10.3%), effect of pregnancy on epilepsy (7.4%), preconception counseling (10.3%), bone health (5.9%), catamenial epilepsy (7.4%), menopause and hormonal replacement therapy (2.9%), contraception (14.7%), menstrual disorders and infertility (8.8%), eclampsia (2.9%), breastfeeding (4.4%), folic acid and vitamin K (5.9%), counseling on general issues (14.7%), and sexuality (4.4%).
Using consensual knowledge lists might promote congruence in educating and/or training community pharmacists on women\'s issues in epilepsy. Future studies are needed to investigate if such lists can improve health services provided to women with epilepsy (WWE).

Current guidelines on cerebral venous thrombosis (CVT) diagnosis and management were issued by the European Federation of Neurological Societies in 2010. We aimed to update the previous European Federation of Neurological Societies guidelines using a clearer and evidence-based methodology.
We followed the Grading of Recommendations, Assessment, Development and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews and writing recommendations based on the quality of available scientific evidence.
We suggest using magnetic resonance or computed tomographic angiography for confirming the diagnosis of CVT and not routinely screening patients with CVT for thrombophilia or cancer. We recommend parenteral anticoagulation in acute CVT and decompressive surgery to prevent death due to brain herniation. We suggest preferentially using low-molecular-weight heparin in the acute phase and not direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that, in women who have suffered a previous CVT, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low-molecular-weight heparin should be considered throughout pregnancy and puerperium.
Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of CVT.