To update the 2000 American Academy of Neurology (AAN) practice parameter on anticonvulsant prophylaxis in patients with newly diagnosed brain tumors.
Following the 2017 AAN methodologies, a systematic literature review utilizing PubMed, EMBASE Library, Cochrane, and Web of Science databases was performed. The studies were rated based on the AAN therapeutic or causation classification of evidence (class I-IV).
Thirty-seven articles were selected for final analysis. There were limited high-level, class I studies and mostly class II and III studies. The AAN affirmed the value of these guidelines.
In patients with newly diagnosed brain tumors who have not had a seizure, clinicians should not prescribe antiepileptic drugs (AEDs) to reduce the risk of seizures (level A). In brain tumor patients undergoing surgery, there is insufficient evidence to recommend prescribing AEDs to reduce the risk of seizures in the peri- or postoperative period (level C). There is insufficient evidence to support prescribing valproic acid or levetiracetam with the intent to prolong progression-free or overall survival (level C). Physicians may consider the use of levetiracetam over older AEDs to reduce side effects (level C). There is insufficient evidence to support using tumor location, histology, grade, molecular/imaging features when deciding whether or not to prescribe prophylactic AEDs (level U).

BACKGROUND: To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019.
METHODS: The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords.
RESULTS: The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year.
CONCLUSIONS: The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.

A pattern of major and minor congenital anomalies, facial dysmorphic features, and neurodevelopmental difficulties, including cognitive and social impairments has been reported in some children exposed to sodium valproate (VPA) during pregnancy. Recognition of the increased risks of in utero exposure to VPA for congenital malformations, and for the neurodevelopmental effects in particular, has taken many years but these are now acknowledged following the publication of the outcomes of several prospective studies and registries. As with other teratogens, exposure to VPA can have variable effects, ranging from a characteristic pattern of major malformations and significant intellectual disability to the other end of the continuum, characterised by facial dysmorphism which is often difficult to discern and a more moderate effect on neurodevelopment and general health. It has become clear that some individuals with FVSD have complex needs requiring multidisciplinary care but information regarding management is currently lacking in the medical literature.
An expert group was convened by ERN-ITHACA, the European Reference Network for Congenital Malformations and Intellectual Disability comprised of professionals involved in the care of individuals with FVSD and with patient representation. Review of published and unpublished literature concerning management of FVSD was undertaken and the level of evidence from these sources graded. Management recommendations were made based on strength of evidence and consensus expert opinion, in the setting of an expert consensus meeting. These were then refined using an iterative process and wider consultation.
Whilst there was strong evidence regarding the increase in risk for major congenital malformations and neurodevelopmental difficulties there was a lack of high level evidence in other areas and in particular in terms of optimal clinical management.. The expert consensus approach facilitated the formulation of management recommendations, based on literature evidence and best practice. The outcome of the review and group discussions leads us to propose the term Fetal Valproate Spectrum Disorder (FVSD) as we feel this better encompasses the broad range of effects seen following VPA exposure in utero.
The expert consensus approach can be used to define the best available clinical guidance for the diagnosis and management of rare disorders such as FVSD. FVSD can have medical, developmental and neuropsychological impacts with life-long consequences and affected individuals benefit from the input of a number of different health professionals.

Attention-deficit/hyperactivity disorder (ADHD) is a common and challenging comorbidity affecting many children with epilepsy. A working group under the International League Against Epilepsy (ILAE) Pediatric Commission identified key questions on the identification and management of ADHD in children with epilepsy. Systematic reviews of the evidence to support approaches to these questions were collated and graded using criteria from the American Academy of Neurology Practice Parameter. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements were followed, with PROSPERO registration (CRD42018094617). No increased risk of ADHD in boys with epilepsy compared to girls with epilepsy was found (Level A). Valproate use in pregnancy is associated with inattentiveness and hyperactivity in offspring (1 class I study), and children with intellectual and developmental disabilities are at increased risk of ADHD (Level A). Impact of early seizure onset on development of ADHD was unclear (Level U), but more evident with poor seizure control (Level B). ADHD screening should be performed from 6 years of age, or at diagnosis, and repeated annually (Level U) and reevaluated after change of antiepileptic drug (AED) (Level U). Diagnosis should involve health practitioners with expert training in ADHD (Level U). Use of the Strength and Difficulties Questionnaire screening tool is supported (Level B). Formal cognitive testing is strongly recommended in children with epilepsy who are struggling at school (Level U). Behavioral problems are more likely with polytherapy than monotherapy (Level C). Valproate can exacerbate attentional issues in children with childhood absence epilepsy (Level A). Methylphenidate is tolerated and effective in children with epilepsy (Level B). Limited evidence supports that atomoxetine is tolerated (Level C). Multidisciplinary involvement in transition and adult ADHD clinics is essential (Level U). In conclusion, although recommendations could be proposed for some of the study questions, this systematic review highlighted the need for more comprehensive and targeted large-population prospective studies.

OBJECTIVE: Laboratories sometimes use different reference ranges for the same antiepileptic drug (AED), particularly for new and poorly investigated drugs. This may contribute to misunderstandings, concerns or inappropriate dose changes, which in turn may affect therapeutic effect, drug safety or treatment adherence. Therefore, the Norwegian Association of Clinical Pharmacology wished to update and harmonize the reference ranges for AEDs and establish national guidelines for Norway.
METHODS: A working group collected information on the reference ranges used by Norwegian laboratories for all commonly used AEDs. These reference ranges were compared to recent recommendations by the International League Against Epilepsy, current literature, applicable clinical studies, reference ranges used by leading Northern European epilepsy centers outside of Norway, and routine data derived from Norwegian laboratory databases.
RESULTS: Reference ranges varied between laboratories for four of 23 available AEDs (lamotrigine, valproate, eslicarbazepine and oxcarbazepine). For four AEDs (brivaracetam, perampanel, stiripentol and sulthiame), reference ranges had not previously been established. In total, 13 reference ranges were either harmonized, updated or newly established. No changes were applied to the remaining 10 AEDs.
CONCLUSIONS: Updated and harmonized reference ranges are now available for 22 of the 23 AEDs available in Norway. The exception is vigabatrin (reference range not applicable). Revision of reference ranges is an important part of pharmacovigilance of AEDs and must be a continuous process based on current literature and clinical experience.

BACKGROUND: Very little has been written on seizure management in palliative care (PC). Given this situation, and considering the forthcoming setting up of the Palliative Care Unit at our neurorehabilitation centre, the Clínica San Vicente, we decided to establish a series of guidelines on the use of antiepileptic drugs (AEDs) for handling seizures in PC.
METHODS: We conducted a literature search in PubMed to identify articles, recent manuals, and clinical practice guidelines on seizure management in PC published by the most relevant scientific societies.
RESULTS: Clinical practice guidelines are essential to identify patients eligible for PC, manage seizures adequately, and avoid unnecessary distress to these patients and their families. Given the profile of these patients, we recommend choosing AEDs with a low interaction potential and which can be administered by the parenteral route, preferably intravenously. Diazepam and midazolam appear to be the most suitable AEDs during the acute phase whereas levetiracetam, valproic acid, and lacosamide are recommended for refractory cases and long-term treatment.
CONCLUSIONS: These guidelines provide general recommendations that must be adapted to each particular clinical case. Nevertheless, we will require further well-designed randomised controlled clinical trials including large samples of patients eligible for PC to draft a consensus document recommending adequate, rational, and effective use of AEDs, based on a high level of evidence, in this highly complex area of medical care.