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We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol, cenobamate, clobazam, eslicarbazepine-acetate, everolimus, felbamate, fenfluramine, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin. For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short- and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman's specific ASM treatment.

GRIA3 at Xq25 encodes glutamate ionotropic receptor AMPA type 3 (GluA3), a subunit of postsynaptic glutamate-gated ion channels mediating neurotransmission. Hemizygous loss-of-function (LOF) variants in GRIA3 cause a neurodevelopmental disorder (NDD) in male individuals. Here, we report a gain-of-function (GOF) variant at GRIA3 in a male patient. We identified a hemizygous de novo missense variant in GRIA3 in a boy with an NDD: c.1844C > T (p.Ala615Val) using whole-exome sequencing. His neurological signs, such as hypertonia and hyperreflexia, were opposite to those in previous cases having LOF GRIA3 variants. His seizures and hypertonia were ameliorated by carbamazepine, inhibiting glutamate release from presynapses. Patch-clamp recordings showed that the human GluA3 mutant (p.Ala615Val) had slower desensitization and deactivation kinetics. A fly line expressing a human GluA3 mutant possessing our variant and the Lurcher variant, which makes ion channels leaky, showed developmental defects, while one expressing a mutant possessing either of them did not. Collectively, these results suggest that p.Ala615Val has GOF effects. GRIA3 GOF variants may cause an NDD phenotype distinctive from that of LOF variants, and drugs suppressing glutamatergic neurotransmission may ameliorate this phenotype. This study should help in refining the clinical management of GRIA3-related NDDs.

Objective To evaluate and compare the effects of concomitant lamotrigine (LTG) or carbamazepine (CBZ) on the incidence of treatment-emergent adverse events (TEAEs) in patients taking adjunctive eslicarbazepine acetate (ESL) for focal (partial-onset) seizures (FS). Methods These post-hoc analyses of data pooled from three randomized, double-blind, placebo-controlled studies of adjunctive ESL (BIA-2093-301, −302 and −304) included adults (≥16 years) with FS refractory to 1–3 antiepileptic drugs (AEDs). Patients were randomized equally to placebo, ESL 400 mg (Studies 301 and 302 only), 800 mg, or 1200 mg once daily (8-week baseline, 2-week titration, and 12-week maintenance periods). TEAEs, TEAEs leading to discontinuation, and serious AEs (SAEs) were evaluated in patients taking, or not taking, LTG (excluding those taking CBZ or phenytoin [PHT]; i.e., the +LTG and −LTG/–CBZ subgroups), or CBZ (excluding those taking LTG or PHT; i.e., the +CBZ and −LTG/–CBZ subgroups) at baseline. Results LTG was used concomitantly by 248 patients (+LTG; placebo, n = 81; ESL, n = 167) and CBZ by 613 patients (+CBZ; placebo, n = 172; ESL, n = 441); 361 patients were taking neither LTG nor CBZ (−LTG/–CBZ; placebo, n = 109; ESL, n = 252). The overall incidence of TEAEs with ESL (any dose) was numerically higher for +CBZ (77%) than for +LTG (73%) or –LTG/–CBZ (68%; statistical significance not tested). Among patients taking ESL, dizziness, diplopia, and vomiting were reported more frequently in the +CBZ subgroup (30%, 14%, and 10%, respectively) than in the +LTG (16%, 8%, 5%) or –LTG/–CBZ (11%, 3%, 5%) subgroups. The overall incidence of TEAEs leading to discontinuation with ESL was higher for +CBZ (21%) than for +LTG (13%) or –LTG/–CBZ (15%). Dizziness leading to discontinuation with ESL was reported more frequently in the +CBZ subgroup than in the +LTG or –LTG/–CBZ subgroups (9%, 3%, and 3%, respectively). The overall incidence of SAEs in patients taking ESL was comparable across subgroups (+LTG, 5%; +CBZ, 6%; –LTG/–CBZ, 5%). The results were similar when evaluating placebo-adjusted incidences. Conclusion There was a potential pharmacodynamic interaction between AEDs with a putatively similar mechanism of action, with a seemingly lesser interaction between ESL and LTG versus ESL and CBZ. If combining ESL with LTG or CBZ, clinicians should be aware of the potential risk for an increased incidence of TEAEs typically associated with voltage-gated sodium channel inhibitors (e.g., dizziness, blurred vision, vertigo, diplopia, headache, or vomiting).

Background The so called “severe neonatal epilepsies with suppression-burst pattern” include early infantile epileptic encephalopathy, and early myoclonic encephalopathy. Both syndromes are characterized by pharmacoresistant seizures that appear in the first weeks (up to the third month) of life, an electroencephalographic suppression-burst pattern, and a grim prognosis. Many patients later present with other forms of epileptic encephalopathies with difficult-to-treat seizures, such as West syndrome, and those who survive usually suffer from severe neurodevelopmental troubles. We here report the case of a patient who presented at our center with features consistent with a mixed form of these epileptic encephalopathies, and favorable neurodevelopmental evolution. Aims To draw attention on the potentially favorable effect of vigabatrin in early-onset epileptic encephalopathies. Methods Case study. Results In our patient, seizures immediately stopped upon initiation of vigabatrin treatment, and his development and neurological examination at one year are normal. Conclusions Vigabatrin should be considered as an early treatment option in early-onset epileptic encephalopathies.

Interleukin-5 contributes both in eosinophilopoiesis and neural development. Serum interleukin-5 levels were measured with enzyme-linked immunosorbent assay technique in 68 children with epilepsy receiving sodium valproate monotherapy and compared with the levels of 60 healthy controls and 14 children with epilepsy receiving carbamazepine. Eosinophilia was observed in 35.3% of children receiving valproate. Interleukin-5 in valproate users was significantly higher compared with children receiving carbamazepine and controls. Valproate users who exhibited eosinophilia had higher interleukin-5 levels compared with those without eosinophilia. However, the interleukin-5 level was also elevated, although to a lesser degree, in children without eosinophilia. The majority of valproate responders had high interleukin-5 levels. A positive correlation between interleukin-5 levels and the eosinophil count was also noted. We postulate that valproate contributes to the pathogenesis of eosinophilia, probably inducing interleukin-5 production. The finding that serum interleukin-5 was significantly elevated in valproate responders and even in valproate users without eosinophilia suggests that the increase in interleukin-5 might Sodium valproate is a simple branched-chain fatty acid that has anticonvulsant activity and is widely used in the treatment of epilepsy and convulsive disorders in children, such as generalized tonic-clonic seizures, absence seizures, myoclonic epilepsy, and partial seizures.1 The side effects of valproate in children include gastrointestinal disturbances, hyperphagia, weight gain, alopecia, hepatotoxicity, tremor, behavioral changes, and hematologic toxicity. Thrombocytopenia is a known hematopoietic side effect of valproate monotherapy that can lead to dosage modification or discontinuation. On the other hand, eosinophilia is a side effect that has not been well studied. In a cohort of 134 adult patients treated with valproate, eosinophilia was a noticeable side effect (30%).2 Eosinophilia caused by drugs is usually benign but can sometimes be accompanied by tissue damage, as in hypersensitivity pneumonitis and hypereosinophilic syndrome.3 Recently, a case of eosinophilic pleural effusion with peripheral blood eosinophilia, which was associated with valproate administration, was reported.4 The development and function of both eosinophil precursors and mature eosinophils are mainly regulated by interleukin-5. There is increasing evidence that the secondary eosinophilia present in patients with allergic and parasitic diseases is due to the production of interleukin-5 by activated T cells.5,6 The objective of the present study was to investigate the possible role of interleukin-5 in the production of eosinophilia that occurs in children with epilepsy receiving valproate monotherapy. J Child Neurol

Higier first reported on "Paroxysmal appearing palsy of epileptic origin". This syndrome has only rarely been described under a variety of names such as: "focal inhibitory seizures, unilateral atonic seizures, hemiparetic seizures, ictal hemiparesis". The case report we present regards a 34-year-old woman who complained of sudden loss of tone accompanied by a left-sided hemiplegia lasting for several minutes. Treatment with carbamazepine was successful in reducing the attacks as might be expected in partial seizures. An inhibitory discharge may be causative of this syndrome in agreement with Higier's original theory.