The ILAE classification of seizures and the epilepsies : Modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures

Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic-only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic-only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non-motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group.Peer reviewe

Treatment of seizures in the neonate: Guidelines and consensus-based recommendations—Special report from the ILAE Task Force on Neonatal Seizures

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic–ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options

KCNT1- related epilepsy: An international multicenter cohort of 27 pediatric cases

ObjectiveThrough international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1- related epilepsy and explored genotype- phenotype correlations associated with frequently encountered variants.MethodsA cross- sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics.ResultsTwenty- seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two- thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray- white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%- 50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy.SignificanceOur cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence- based practice is still unavailable.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154940/1/epi16480_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154940/2/epi16480.pd

Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies

An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising as an intranasal delivery system for controlling acute seizures. Three different nanosized phenytoin sodium loaded NLCs (<50 nm, 50–100 nm and >100 nm) were prepared by melt emulsification and was further characterised. In vitro drug release studies showed immediate drug release from phenytoin sodium loaded NLCs of <50 nm size, which is highly essential for acute seizure control. The ex vivo permeation study indicated greater permeation from <50 nm sized NLC through the olfactory epithelium compared to thecontrol drug solution. Invivo pharmacokinetic studies revealed higher drug concentration in CSF/brain within 5 min upon intranasal administration of <50 nm sized phenytoin sodium NLCs than the control drug solution and marketed IV phenytoin sodium, indicating direct and rapid nose to brain drug transport through the olfactory epithelium. The study has shown that formulation strategies can enhance olfactory uptake, and phenytoin sodium NLCs of desired particle sizes (<50 nm) offer promising potential for nose to brain direct delivery of phenytoin sodium in treating acute epileptic seizures

Clinical profile and treatment outcome of febrile infection-related epilepsy syndrome in South Indian children

Purpose: To describe the clinical features and outcome of febrile infection-related epilepsy syndrome (FIRES), a catastrophic epileptic encephalopathy, in a cohort of South Indian children. Materials and Methods: We performed a retrospective chart review of a cohort of children with previously normal development who presented with status epilepticus or encephalopathy with recurrent seizures following a nonspecific febrile illness during the period between January 2007 and January 2012. They were divided into two groups super refractory status epilepticus (SRSE) and refractory status epilepticus (RSE) depending on the duration and severity of the seizures. Key Findings: Fifteen children who met the inclusion criteria were included for the final analysis. The age of the children at presentation ranged 3-15 years (median 6.3 years). All the children presented with prolonged or recurrent seizures occurring 1-12 days (median 4 days) after the onset of fever. Eight children had SRSE while seven children had refractory seizures with encephalopathy. Cerebrospinal fluid (CSF) analysis was done in all the children in the acute phase, and the cell count ranged 0-12 cells/μL (median 2 cells/μL) with normal sugar and protein levels. Initial neuroimaging done in all children (MRI in 10 and CT in 5), and it was normal in 13 children. Treatment modalities included multiple antiepileptic drugs (AEDs) (4-9 drugs) (median 5 drugs). Midazolam (MDZ) infusion was administered in seven patients. Eight patients required barbiturate coma to suppress the seizure activity. The duration of the barbiturate coma ranged 2-90 days (median 3 days). Steroids were used in 14 children and intravenous immunoglobulin (2 g/kg) in 7 children. Three children died in the acute phase. All children were maintained on multiple AEDs till the last follow-up, the number of AEDs ranged 1-6 (median 5 AEDs). The patients with super refractory status in the acute phase were found to be more severely disabled at the follow-up; the median score of these patients on the Glasgow Outcome Scale (GOS) was 2 compared to 5 in the RSE group. Significance: This study reports one of the largest single center cohorts from India, with an adverse long-term developmental and seizure outcome. The duration and severity of seizures in the acute period correlated directly with the short-term and long-term clinical outcomes. There is an urgent need for developing new effective therapeutic strategies to treat this acute catastrophic epileptic syndrome

The ILAE classification of seizures and the epilepsies: Modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures

Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic-only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic-only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non-motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group.Peer reviewe

Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics

Summary Evidence-based guidelines, or recommendations, for the management of infants with seizures are lacking. A Task Force of the Commission of Pediatrics developed a consensus document addressing diagnostic markers, management interventions, and outcome measures for infants with seizures. Levels of evidence to support recommendations and statements were assessed using the American Academy of Neurology Guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The report contains recommendations for different levels of care, noting which would be regarded as standard care, compared to optimal care, or "state of the art" interventions. The incidence of epilepsy in the infantile period is the highest of all age groups (strong evidence), with epileptic spasms the largest single subgroup and, in the first 2 years of life, febrile seizures are the most commonly occurring seizures. Acute intervention at the time of a febrile seizure does not alter the risk for subsequent epilepsy (class 1 evidence). The use of antipyretic agents does not alter the recurrence rate (class 1 evidence), and there is no evidence to support initiation of regular antiepileptic drugs for simple febrile seizures (class 1 evidence). Infants with abnormal movements whose routine electroencephalography (EEG) study is not diagnostic, would benefit from video-EEG analysis, or home video to capture events (expert opinion, level U recommendation). Neuroimaging is recommended at all levels of care for infants presenting with epilepsy, with magnetic resonance imaging (MRI) recommended as the standard investigation at tertiary level (level A recommendation). Genetic screening should not be undertaken at primary or secondary level care (expert opinion). Standard care should permit genetic counseling by trained personal at all levels of care (expert opinion). Genetic evaluation for Dravet syndrome, and other infantile-onset epileptic encephalopathies, should be available in tertiary care (weak evidence, level C recommendation). Patients should be referred from primary or secondary to tertiary level care after failure of one antiepileptic drug (standard care) and optimal care equates to referral of all infants after presentation with a seizure (expert opinion, level U evidence). Infants with recurrent seizures warrant urgent assessment for initiation of antiepileptic drugs (expert opinion, level U recommendation). Infantile encephalopathies should have rapid introduction and increment of antiepileptic drug dosage (expert opinion, level U recommendation). There is no high level evidence to support any particular current agents for use in infants with seizures. For focal seizures, levetiracetam is effective (strong evidence); for generalized seizures, weak evidence supports levetiracetam, valproate, lamotrigine, topiramate, and clobazam; for Dravet syndrome, strong evidence supports that stiripentol is effective (in combination with valproate and clobazam), whereas weak evidence supports that topiramate, zonisamide, valproate, bromide, and the ketogenic diet are possibly effective; and for Ohtahara syndrome, there is weak evidence that most antiepileptic drugs are poorly effective. For epileptic spasms, clinical suspicion remains central to the diagnosis and is supported by EEG, which ideally is prolonged (level C recommendation). Adrenocorticotropic hormone (ACTH) is preferred for short-term control of epileptic spasms (level B recommendation), oral steroids are probably effective in short-term control of spasms (level C recommendation), and a shorter interval from the onset of spasms to treatment initiation may improve long-term neurodevelopmental outcome (level C recommendation). The ketogenic diet is the treatment of choice for epilepsy related to glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency (expert opinion, level U recommendation). The identification of patients as potential candidates for epilepsy surgery should be part of standard practice at primary and secondary level care. Tertiary care facilities with experience in epilepsy surgery should undertake the screening for epilepsy surgical candidates (level U recommendation). There is insufficient evidence to conclude if there is benefit from vagus nerve stimulation (level U recommendation). The key recommendations are summarized into an executive summary. The full report is available as Supporting Information. This report provides a comprehensive foundation of an approach to infants with seizures, while identifying where there are inadequate data to support recommended practice, and where further data collection is needed to address these deficits.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe