Eija Gaily

Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy.

Summary: Purpose: To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and poly‐therapy.

Normal intelligence in children with prenatal exposure to carbamazepine

Objective: To investigate the effect of antiepileptic drugs, especially carbamazepine and valproate, on intelligence in prenatally exposed children of mothers with epilepsy. Methods: Intelligence of 182 children of mothers with epilepsy (study group) and 141 control children was tested in a blinded setting at preschool or school age using Wechsler Preschool and Primary Scale of Intelligence–Revised or Wechsler Intelligence Scale for Children–Revised. Data on maternal antiepileptic treatment and seizures during pregnancy were gathered prospectively. The study group represented approximately 50% of the children born to mothers with epilepsy in Uusimaa province during 1989 through1994. One hundred seven children were exposed to antiepileptic monotherapy: 86 to carbamazepine and 13 to valproate. Thirty children were exposed to polytherapy: 23 combinations included carbamazepine, and 17 included valproate. The median maternal doses and blood levels during the second half of pregnancy were 600 mg and 26 μmol/L for carbamazepine and 950 mg and 300 μmol/L for valproate. Results: The mean verbal and nonverbal IQ scores in the children exposed in utero to carbamazepine monotherapy were 96 (95% CI, 93–100) and 103 (95% CI, 100–106). They did not differ from control subjects, whose mean verbal and nonverbal IQ scores were 95 (95% CI, 92–97) and 102 (95% CI, CI, 100–105). Significantly reduced verbal IQ scores were found in children exposed to valproate (mean, 82; 95% CI, 78–87) and to polytherapy (mean, 85; 95% CI, 80–90) compared with the other study group children and control subjects. Conclusions: Carbamazepine monotherapy with maternal serum levels within the reference range does not impair intelligence in prenatally exposed offspring. Exposures to polytherapy and to valproate during pregnancy were associated with significantly reduced verbal intelligence. The independent effects of valproate remain unconfirmed because the results were confounded by low maternal education and polytherapy.

SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain

Background: Inherited and de novo mutations in sodium channel genes underlie a variety of channelopathies. Mutations in SCN2A, encoding the brain sodium channel NaV1.2, have previously been reported to be associated with benign familial neonatal infantile seizures, febrile seizures plus, and intractable epilepsy of infancy. Methods: We evaluated the clinical characteristics in a patient with a neonatal-onset complex episodic neurologic phenotype. We screened SCN2A for mutations and carried out in vitro electrophysiologic analyses to study the consequences of the identified mutation. We studied the developmental expression of NaV1.2 in cerebellum by immunohistochemical analysis. Results: The patient presented with neonatal-onset seizures and variable episodes of ataxia, myoclonia, headache, and back pain after 18 months of age. The patient carries a de novo missense mutation (p.Ala263Val) in SCN2A, which leads to a pronounced gain-of-function, in particular an increased persistent Na+ current. Immunohistochemical studies suggest a developmentally increasing expression of NaV1.2 in granule cell axons projecting to Purkinje neurons. Conclusions: These results can explain a neuronal hyperexcitability resulting in seizures and other episodic symptoms extending the spectrum of SCN2A-associated phenotypes. The developmentally increasing expression of NaV1.2 in cerebellum may be responsible for the later onset of episodic ataxia.

Valproate in the treatment of epilepsy in girls and women of childbearing potential

This document provides guidance on the use of valproate in girls and women of childbearing age from a joint Task Force of the Commission on European Affairs of the International League Against Epilepsy (CEA‐ILAE) and the European Academy of Neurology (EAN), following strengthened warnings from the Coordination Group for Mutual Recognition and Decentralised Procedures‐Human (CMDh) of the European Medicines Agency (EMA), which highlight the risk of malformations and developmental problems in infants who are exposed to valproate in the womb. To produce these recommendations, the Task Force has considered teratogenic risks associated with use of valproate and treatment alternatives, the importance of seizure control and of patient and fetal risks with seizures, and the effectiveness of valproate and treatment alternatives in the treatment of different epilepsies. The Task Forces recommendations include the following: (1) Where possible, valproate should be avoided in women of childbearing potential. (2) The choice of treatment for girls and women of childbearing potential should be based on a shared decision between clinician and patient, and where appropriate, the patients representatives. Discussions should include a careful risk–benefit assessment of reasonable treatment options for the patients seizure or epilepsy type. (3) For seizure (or epilepsy) types where valproate is the most effective treatment, the risks and benefits of valproate and other treatment alternatives should be discussed. (4) Valproate should not be prescribed as a first‐line treatment for focal epilepsy. (5) Valproate may be offered as a first‐line treatment for epilepsy syndromes where it is the most effective treatment, including idiopathic (genetic) generalized syndromes associated with tonic–clonic seizures. (6) Valproate may be offered as a first‐line treatment in situations where pregnancy is highly unlikely (e.g., significant intellectual or physical disability). (7) Women and girls taking valproate require regular follow‐up for ongoing consideration of the most appropriate treatment regimen.

Treatment of infantile spasms : Results of a population-based study with vigabatrin as the first drug for spasms

Summary: Purpose: The efficacy of a protocol consisting of vigabatrin (VGB) as the first and adrenocorticotropic hormone (ACTH) or valproate (VPA) as the second drug was studied in the treatment of newly diagnosed infantile spasms (IS) during 1994 to 1997 in a population‐based design.

Long‐term outcome of 32 children with encephalopathy with status epilepticus during sleep, or ESES syndrome

Purpose:  To prospectively evaluate the efficacy of drug treatment and long‐term cognitive outcome in children with encephalopathy with status epilepticus during sleep (ESESS).

Asymmetric and Asynchronous Infantile Spasms

Summary: Infantile spasms most commonly show symmetric behavioral and electroencephalogram (EEG) manifestations. Asymmetric and asynchronous behavioral spasms occur occasionally, but their relationship to ictal EEG and to other localizing studies has not received much attention. We reviewed 75 consecutive video‐EEG recordings, done at UCLA from 1982 to 1992, that contained infantile spasms; 8,680 spasms were scored for behavioral and EEG asymmetry and asynchrony. Of the recorded spasms, 25% were asymmetric and 7% were asynchronous. Most asymmetric or asynchronous spasms were associated with an ictal EEG discharge that was contralateral to the behaviorally more involved side. In 12 of the 60 patients (20%), more than half of the recorded spasms were asymmetric or asynchronous,. Baseline EEG, magnetic resonance imaging, positron emission tomography, and neurological examination revealed structural and functional brain abnormalities that involved the contralateral central region significantly more often in the children with >50% spasm asymmetry or asynchrony than in the other children. Partial seizures with lateralized motor behavior also occurred frequently in these children. The findings suggest that asymmetric and asynchronous spasms are generated by a cortical epileptogenic region that involves the primary sensorimotor area. The combination of asymmetric and asynchronous infantile spasms, partial motor seizures involving the same side of the body, and pathology in the contralateral central region may represent a unique subset of symptomatic localization‐related infantile epilepsy.

Five percent CO2 is a potent, fast-acting inhalation anticonvulsant

Purpose:  CO2 has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO2 can be used to suppress seizures in epilepsy patients. The effect of CO2 on cortical epileptic activity accompanying behavioral seizures was studied in rats and nonhuman primates, and based on these data, preliminary tests were carried out in humans.

Visual fields at school-age in children treated with vigabatrin in infancy.

Purpose:  The use of vigabatrin (VGB) as an antiepileptic drug (AED) has been limited by evidence showing that it causes vigabatrin‐attributed visual field loss (VAVFL) in at least 20–40% of patients exposed at school age or later. VGB is an effective drug for infantile spasms, but there are no reports on later visual field testing after such treatment. Our aim was to investigate the risk of VAVFL in school‐age children who had received VGB in infancy.

Proton Spectroscopic Imaging Shows Abnormalities in Glial and Neuronal Cell Pools in Frontal Lobe Epilepsy

Summary:  Purpose: Proton magnetic resonance spectroscopic imaging (1H MRSI) can lateralize the epileptogenic frontal lobe by detecting metabolic ratio abnormalities in frontal lobe epilepsy (FLE). We used 1H MRS to lateralize and localize the epileptogenic focus, and we also sought to characterize further the metabolic abnormality in FLE.