Rapid and safe response to low-dose carbamazepine in neonatal epilepsy.

OBJECTIVE: To evaluate treatment responses in benign familial neonatal epilepsy (BFNE). METHODS: We recruited patients with BFNE through a multicenter international collaboration and reviewed electroclinical and genetic details, and treatment response. All patients were tested at minimum for mutations/deletions in the KCNQ2, KCNQ3, and SCN2A genes. RESULTS: Nineteen patients were included in this study. A family history of neonatal seizures was positive in 16 patients, and one additional patient had a family history of infantile seizures. Mutations or deletions of KCNQ2 were found in 14, and of KCNQ3 in 2, of the 19 patients. In all patients, seizures began at 2-5 days of life and occurred multiple times per day. Four patients developed status epilepticus. Seizures were focal, alternating between hemispheres, and characterized by asymmetric tonic posturing associated with apnea and desaturation, followed by unilateral or bilateral asynchronous clonic jerking. Twelve of 19 patients were treated with multiple medications prior to seizure cessation. Seventeen of (88%) 19 patients were seizure-free within hours of receiving oral carbamazepine (CBZ) or oxcarbazepine (OXC). Earlier initiation of CBZ was associated with shorter hospitalization (p < 0.01). No side effects of CBZ were reported. All patients had normal development and remain seizure-free at a mean follow-up period of 7.8 years (6 months-16 years). SIGNIFICANCE: This study provides evidence that CBZ is safe and rapidly effective in neonates with BFNE, even in status epilepticus. We propose that CBZ should be the drug of choice in benign familial neonatal seizures.

Neonatal Seizures: An Overview of Genetic Causes and Treatment Options.

Seizures are the most frequent neurological clinical symptoms of the central nervous system (CNS) during the neonatal period. Neonatal seizures may be ascribed to an acute event or symptomatic conditions determined by genetic, metabolic or structural causes, outlining the so-called 'Neonatal Epilepsies'. To date, three main groups of neonatal epilepsies are recognised during the neonatal period: benign familial neonatal epilepsy (BFNE), early myoclonic encephalopathy (EME) and 'Ohtahara syndrome' (OS). Recent advances showed the role of several genes in the pathogenesis of these conditions, such as KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A and SCN8A. Herein, we reviewed the current knowledge regarding the pathogenic variants most frequently associated with neonatal seizures, which should be considered when approaching newborns affected by these disorders. In addition, we considered the new possible therapeutic strategies reported in these conditions.

A novel mutation in KCNQ3-related benign familial neonatal epilepsy: electroclinical features and neurodevelopmental outcome.

Benign familial neonatal epilepsy (BFNE) is caused, in about 5% of families, by mutations in the KCNQ3 gene encoding voltage-gated potassium channel subunits. Usually, newborns with BFNE show a normal neurological outcome, but recently, refractory seizures and/or developmental disability have been reported suggesting phenotype variability associated with KCNQ3-related BFNE. Here, we describe a proband from a BFNE family carrying a novel variant in the KCNQ3 gene. Regarding the paucity of data in the literature, we describe the presented case with a view to further establishing: (1) a genotype/phenotype correlation in order to define a BFNE phenotype associated with favourable outcome; (2) an electroclinical pattern associated with BFNE based on video-EEG recording; (3) appropriate first-line AEDs; and (4) the duration of AED treatment. The presented case from Day 3 exhibited a cluster of ictal events, identified as epileptic seizures on Day 10 based on continuous video-EEG polygraphy. The seizures were characterized by asymmetric tonic posturing, associated with a generalized decrease in EEG amplitude, and followed by bilateral asynchronous clonic movements associated with bicentral sharp-wave discharges. The seizures were refractory to intravenous pyridoxine, whereas levetiracetam resulted in rapid total seizure control which has remained to date. This study demonstrates that the novel heterozygous KCNQ3 (c. 914A>T; p.Asp305Val) variant, affecting residues in the pore region, is associated with a specific electroclinical pattern and favourable neurodevelopmental outcome. [Published with video sequence on www.epilepticdisorders.com].

Exacerbation of benign familial neonatal epilepsy induced by massive doses of phenobarbital and midazolam.

BACKGROUND: Barbiturates and benzodiazepines are the first-line anticonvulsants for neonatal seizures. However, in immature brains, those drugs may lead to paradoxical neuronal excitation. PATIENT: A patient with benign familial neonatal epilepsy developed epileptic encephalopathy after massive doses of phenobarbital that were followed by a continuous infusion of midazolam on postnatal day 3. Electroencephalography revealed rhythmic delta activity in clusters with migrating epileptic foci. After discontinuation of both drugs, the patient's consciousness promptly improved and her electroencephalography normalized on postnatal day 5. RESULTS: This baby developed persistent electroencephalographic seizures due to massive doses of phenobarbital and midazolam. CONCLUSION: Clinicians should be aware of this anticonvulsant-induced paradoxical neuronal excitation and the uncoupling phenomenon, especially in individuals with benign familial neonatal epilepsy, who have low seizure thresholds.