Neuropsychological Performance 1 Year After Status Epilepticus in Adults.

OBJECTIVES: Status epilepticus (SE) may lead to or worsen cognitive dysfunction. Few studies have evaluated magnitude and profile of cognitive dysfunction in patients after SE. Characterization of cognitive deficits may be important for rehabilitation and follow-up. We assessed cognitive function in a consecutive, non-selected group of relatively healthy survivors with a comprehensive neuropsychological test battery. METHODS: A total of 33 patients (24 men, 9 women; mean age 54,9 years, mean education 11,8 years) were tested 1 year after SE with Wechsler Adult Intelligence Scale Fourth edition (WAIS-IV), Rey Auditory Verbal Learning Test, subtests from the Wechsler Memory Scale-Revised, Phonemic and Semantic word list generation, and the Halstead-Reitan Battery. Premorbid IQ was estimated with a Norwegian version of the National Adult Reading Test (NART). Results were compared to published norms. Regression analyses and independent groups t-tests were performed to assess the influence of background variables. RESULTS: Mean performance generally was about one standard deviation below average. Full scale IQ (WAIS-IV) was significantly reduced compared to estimated premorbid IQ (NART). Negative influence on cognition of brain lesions visible on computed tomography or magnetic resonance imaging and duration of SE >30 min was shown by group comparisons. CONCLUSIONS: SE represents a marker for possible cognitive dysfunction, and follow-up with neuropsychological assessment and cognitive rehabilitation seems warranted in most patients. Complex problem-solving abilities with high general sensitivity to brain impairment showed the most prominent reduction. Otherwise, no specific profile of domain affection was found. Structural brain lesions and duration of SE over 30 min represent risk factors for cognitive deficit.

Cognitive function after status epilepticus versus after multiple generalized tonic-clonic seizures.

OBJECTIVES: Status epilepticus (SE) is considered a risk for cognitive impairment. Studies have indicated that SE cause more cognitive decline than multiple lifetime generalized tonic clonic (GTC) seizures. The aim of the study was to investigate whether patients suffering from SE or from multiple lifetime GTC seizures have cognitive dysfunction, and if the disabilities differ between these groups. MATERIALS AND METHODS: Patients suffering from SE were evaluated shortly after the clinical post-ictal phase and again after one year. Their follow-up results were compared to results from patients with ≥10 GTC seizures and a group of control subjects. Tests from Cambridge Neuropsychological Test Automated Battery (CANTAB) were used. Motor Screening Test (MOT) assessed motor speed, Delayed Matching to Sample (DMS) and Paired Associates Learning (PAL) assessed memory, and Stockings of Cambridge (SOC) assessed executive function. Estimated premorbid IQ and radiologically visible brain lesions were controlled for in adjusted results. Outcome measures were z-scores, the number of standard deviations a score deviates from the mean of a norm population. Negative z-scores indicate poor performance. RESULTS: After the clinical post-ictal phase, performances of SE patients were poor on all domains (n = 46). Mean z-scores with 95% confidence intervals were below zero for tests of psychomotor speed, executive thinking times and memory. Both SE patients at follow-up (n = 39) and patients with multiple GTC seizures (n = 24) performed poorer than controls (n = 20) on tests of memory. These group differences remained significant after covariate adjustments. SE patients at follow-up scored below patients with multiple GTC seizures on tests of psychomotor speed (mean difference -0.59, P = 0.020), but after adjusting for covariates this difference was no longer significant. CONCLUSIONS: Our data do not allow a firm conclusion as to whether SE is a more pronounced risk factor for cognitive dysfunction than repeated generalized tonic clonic seizures. In both patient groups, memory and learning dysfunction remained significant after adjusting for estimated premorbid IQ and structural brain lesions.

Myoclonus epilepsy and ataxia due to KCNC1 mutation: Analysis of 20 cases and K+ channel properties.

OBJECTIVE: To comprehensively describe the new syndrome of myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK), including cellular electrophysiological characterization of observed clinical improvement with fever. METHODS: We analyzed clinical, electroclinical, and neuroimaging data for 20 patients with MEAK due to recurrent KCNC1 p.R320H mutation. In vitro electrophysiological studies were conducted using whole cell patch-clamp to explore biophysical properties of wild-type and mutant KV 3.1 channels. RESULTS: Symptoms began at between 3 and 15 years of age (median = 9.5), with progressively severe myoclonus and rare tonic-clonic seizures. Ataxia was present early, but quickly became overshadowed by myoclonus; 10 patients were wheelchair-bound by their late teenage years. Mild cognitive decline occurred in half. Early death was not observed. Electroencephalogram (EEG) showed generalized spike and polyspike wave discharges, with documented photosensitivity in most. Polygraphic EEG-electromyographic studies demonstrated a cortical origin for myoclonus and striking coactivation of agonist and antagonist muscles. Magnetic resonance imaging revealed symmetrical cerebellar atrophy, which appeared progressive, and a prominent corpus callosum. Unexpectedly, transient clinical improvement with fever was noted in 6 patients. To explore this, we performed high-temperature in vitro recordings. At elevated temperatures, there was a robust leftward shift in activation of wild-type KV 3.1, increasing channel availability. INTERPRETATION: MEAK has a relatively homogeneous presentation, resembling Unverricht-Lundborg disease, despite the genetic and biological basis being quite different. A remarkable improvement with fever may be explained by the temperature-dependent leftward shift in activation of wild-type KV 3.1 subunit-containing channels, which would counter the loss of function observed for mutant channels, highlighting KCNC1 as a potential target for precision therapeutics. Ann Neurol 2017;81:677-689.

Neuroleptic malignant syndrome: an easily overlooked neurologic emergency.

Neuroleptic malignant syndrome is an unpredictable iatrogenic neurologic emergency condition, mainly arising as an idiosyncratic reaction to antipsychotic agent use. It is characterized by distinctive clinical features including a change in mental status, generalized rigidity, hyperpyrexia, and dysautonomia. It can be lethal if not diagnosed and treated properly. Mortality and morbidity attributed to this syndrome have recently declined markedly due to greater awareness, earlier diagnosis, and intensive care intervention. In most cases, the syndrome occurs as a result of a rapid increase in a dose of neuroleptic, especially one of the long-acting ones. Pathophysiology behind this syndrome is attributed to a dopamine receptor blockade inside the neurons rendered by the offending drug and excessive calcium release from the sarcoplasmic reticulum of skeletal myocytes. Laboratory tests, although not diagnostic, may assist in assessing the severity of the syndrome and also the consequent complications. The syndrome has been described in all age groups and occurs more in males than in females. Genetics appears to be central regarding the etiology of the syndrome. Stopping the use of the offending agent, cold intravenous fluids, and removal of the causative agent and its possible active metabolites is the cornerstone of treatment. Periodic observation of psychotic patients recently started on antipsychotic medications, especially those being treated with depot preparations, may aid to an early diagnosis of the syndrome and lead to early treatment.

Codeine is associated with poor prognosis in acute stroke.

Background: The aim of this study was to investigate how the use of analgesics, sleeping drugs, and sedatives relates to prognosis and complications in stroke patients in the acute care phase (≤48 hr) after a stroke. Materials and Methods: Patients with ischemic stroke, hemorrhagic stroke, and transient ischemic attack were included. The study is based on gathering of data on medication from 921 patient records belonging to patients included in the Bergen NORSTROKE registry, 12.2009-02.2012. In this database risk factors, stroke severity, etiology, and blood analyses were prospectively registered. We have retrospectively registered if patients received one drug or more from a list of analgesics, sleeping drugs, and sedatives within the first 48 hr after admission. Results: In total, 921 patients were included in the study, 408 females and 513 males. Mean age was 71.0 years. In total, 101 patients were given sleeping drugs, 97 patients sedatives and 140 patients analgesics. Of the group given analgesics, 90 patients were given codeine-containing analgesics. Logistic regression analyses showed that codeine-containing analgesics were associated with an increased occurrence of pneumonia (OR = 3.8, p < .001), stroke worsening (OR = 2.7, p = .001), and a higher mRS-score (OR = 2, p = .024) day 7. The study did not show any relation between poorer prognosis or increased occurrence of complications and the use of other analgesics, sedatives and/or sleeping drugs. Conclusion: Use of codeine-containing analgesics is associated with a poorer short-term prognosis and an increased occurrence of complications in the acute phase after a stroke. The highly significant findings suggest that codeine has a negative effect on acute stroke patients. The study reflects exploratory analyses and prospective studies are necessary to determine the background of the association observed in our study.

Life satisfaction in women with epilepsy during and after pregnancy.

OBJECTIVE: The aim of this study was to investigate life satisfaction in women with epilepsy during and after pregnancy. METHODS: The study was based on the Norwegian Mother and Child Cohort Study, including 102,265 women with and without epilepsy from the general population. Investigation took place at pregnancy weeks 15-19 and 6 and 18months postpartum. Women with epilepsy were compared with a reference group without epilepsy. RESULTS: The proportion of women with epilepsy was 0.6-0.7% at all three time points. Women with epilepsy reported lower life satisfaction and self-esteem both during and after pregnancy compared with the references. Single parenting correlated negatively with life satisfaction in epilepsy during the whole study period. Epilepsy was associated with lower levels of relationship satisfaction and higher levels of work strain during pregnancy and lower levels of self-efficacy and satisfactory somatic health 18months postpartum. Adverse life events, such as divorce, were more common in women with epilepsy compared with the references, and fewer women with epilepsy had a paid job 18months postpartum. SIGNIFICANCE: Reduced life satisfaction associated with epilepsy during and after pregnancy showed that, even in a highly developed welfare society, women with epilepsy struggle. Mothers with epilepsy and their partners should be examined for emotional complaints and partnership satisfaction during and after pregnancy. Validated screening tools are available for such measures.

Prognostic factors of status epilepticus in adults.

AIM: Status epilepticus (SE) can lead to sequelae or even death. Identifying characteristics associated with poor outcome is crucial in guiding patient treatment. Based on our retrospective patient cohorts, potential prognostic factors were analysed. METHODS: Patients consecutively treated for refractory convulsive status epilepticus (CSE) between 2001 and 2010 and non-convulsive status epilepticus (NCSE) between 2004 and 2009 were studied. Outcome was compared to prognostic variables. Index SE episodes were used for the statistical analyses. Crosstabs and independent samples t-test were applied. Due to sample size, logistic regression was performed for the combined groups. RESULTS: In total, 50% (9/18) of index refractory CSE and 42% (16/38) of index NCSE episodes led to sequelae. Refractory CSE requiring narcosis for >20 hours was associated with poor outcome (p=0.05). De novo presentation (p=0.0001), long-lasting SE (>2 hours) (p=0.014), age >65 years (p=0.002), and refractory SE (p=0.047) were predictors of poor outcome following NCSE. Based on logistic regression for combined refractory CSE and NCSE, de novo presentation was identified as the strongest predictor of sequelae. CONCLUSIONS: Older age and de novo SE are predictors of sequelae following NCSE. Prolonged SE is a risk factor for poor outcome, both for refractory CSE and NCSE. Aggressive initial treatment to terminate seizures during the early phase is therefore essential.

Status epilepticus secondary to glioma.

PURPOSE: Epilepsy is common in glioma patients, but clinical data on the course of status epilepticus (SE) in this group are sparse. The aim of this study was to investigate the relationship of SE to tumor grading, seizure semiology, trigger factors, treatment response, recurrence and outcome of SE in patients with glioma. METHODS: Adult patients with SE and glioma WHO grade II-IV were identified from a prospective clinical study at two neurological departments. We identified 31 SE in 20 patients during a period of 7 years. RESULTS: SE was more frequent in patients with high-grade glioma. Half of the seizures were secondary generalized. Patients with a clinical and radiological stable glioma had SE as often as patients with untreated tumor or tumor in progression. The majority of patients had a well-controlled epilepsy prior to SE. SE responded well to first and second line treatment. Patients with SE and tumor progression were not more refractory to treatment than patients without progression. CONCLUSION: SE secondary to glioma responded well to treatment and should be treated aggressively regardless of the oncological prognosis. Seizures during tumor progression were not more treatment refractory than SE in patients with stable glioma disease.

Psychiatric Comorbidity, Social Aspects and Quality of Life in a Population-Based Cohort of Expecting Fathers with Epilepsy.

OBJECTIVES: To investigate psychiatric disorders, adverse social aspects and quality of life in men with epilepsy during partner's pregnancy. METHOD: We used data from the Norwegian Mother and Child Cohort Study, including 76,335 men with pregnant partners. Men with epilepsy were compared to men without epilepsy, and to men with non-neurological chronic diseases. RESULTS: Expecting fathers in 658 pregnancies (mean age 31.8 years) reported a history of epilepsy, 36.9% using antiepileptic drugs (AEDs) at the onset of pregnancy. Symptoms of anxiety or depression were increased in epilepsy (7.0% and 3.9%, respectively) vs. non-epilepsy (4.6% and 2.5%, respectively, p = 0.004 and 0.023), and so were new onset symptoms of depression (2.0% vs. 1.0%, p < 0.031) and anxiety (4.3% vs. 2.3%, p = 0.023). Low self-esteem (2.5%) and low satisfaction with life (1.7%) were more frequent among fathers with epilepsy compared to fathers without epilepsy (1.3% and 0.7%, respectively, p = 0.01 and 0.010). Adverse social aspects and life events were associated with epilepsy vs. both reference groups. Self-reported diagnoses of ADHD (2.2%) and bipolar disorder (1.8%) were more common in epilepsy vs. non-epilepsy (0.4% and 0.3%, respectively, p = 0.002 and 0.003) and non-neurological chronic disorders (0.5% and 0.5%, respectively, p = 0.004 and 0.018). A screening tool for ADHD symptoms revealed a higher rate compared to self-reported ADHD (9.5% vs. 2.2%, p < 0.001). CONCLUSION: Expecting fathers with epilepsy are at high risk of depression and anxiety, adverse socioeconomic aspects, low self-esteem, and low satisfaction with life. Focus on mental health in fathers with epilepsy during and after pregnancy is important. The use of screening tools can be particularly useful to identify those at risk.

Epilepsy and recommendations for breastfeeding.

PURPOSE: The objective of this paper is to provide a synopsis of benefits and potential harmful effects of exposure to antiepileptic drugs (AEDs) via breastmilk, and present recommendations for breastfeeding in women with epilepsy. METHODS: The article is based on a discretionary selection of English language articles retrieved by a literature search in the PubMed database, the LactMed database, and the authors' clinical experience. RESULTS: Breastfeeding is associated with benefits for the infant, including nutrition, protection against infectious and immunological disease, and promotion of development and psychological attachment. Exposure to AEDs via breastmilk could potentially produce side effects or negatively affect development. Most studies on AED transfer through breastmilk report infant serum levels well below the limit of an expected pharmacological effect. Some drugs have the potential to reach significant serum levels in breastfed infants, such as barbiturates, benzodiazepines, lamotrigine, and ethosuximide. Thus, breastfed infants should be monitored for side effects. Still, adverse symptoms are rarely reported in breastfed infants of mothers taking AEDs, and prospective studies have failed to demonstrate any negative developmental effects in children that have been exposed to AEDs via breastmilk. The nursing infant's degree of drug exposure can be minimized by breastfeeding when drug concentrations in the milk are low, reducing maternal AED dosage to prepregnancy levels, and administering mixed nutrition. CONCLUSION: Most AEDs are considered safe or moderately safe during breastfeeding. Mothers with epilepsy should be encouraged to breastfeed, provided careful monitoring of the infant.

Adult nonconvulsive status epilepticus in a clinical setting: Semiology, aetiology, treatment and outcome.

PURPOSE: Our objective was to study the semiology, aetiology, treatment and outcome of nonconvulsive status epilepticus (NCSE) in adults. METHODS: All NCSE episodes in an unselected hospital cohort in the period 2004-2009 were identified, and the files reviewed. STESS (Status Epilepticus Severity Scale) was conducted retrospectively and correlated to outcome. Follow-up was undertaken after >2 years. RESULTS: 48 NCSEs in 39 patients, 22 men and 17 women, were found. Mean age was 63 years. 23/39 (59%) patients had established epilepsy. The underlying cause of NCSE was cerebrovascular disease in 17/39 (44%). 37/48 (77%) NCSEs were complex focal status epilepticus. 3/48 NCSEs (6.3%) lead to death, whereas 8.5% lead to severe sequelae. Cognitive sequelae were found after 14.9% of NCSEs. The outcome was worst in the group with no prior epilepsy (p=0.013). STESS had a negative predictive value of 96% (cut-off value of 3) for severe sequelae and death combined (p<0.002). CONCLUSIONS: NCSE has a potential for severe sequelae and represents an emergency in need of intensive treatment. The major determinant of outcome is the underlying cause. The outcome was worse in patients without epilepsy than in patients with epilepsy. STESS is of value in predicting outcome. Cognitive sequelae following NCSE can occur, but need further investigation with prospective, systematic studies.

A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy.

Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo mutation, c.959G>A (p.Arg320His), in KCNC1 was identified as a new major cause for PME. Eleven unrelated exome-sequenced (13%) and two affected individuals in a secondary cohort (7%) had this mutation. KCNC1 encodes KV3.1, a subunit of the KV3 voltage-gated potassium ion channels, which are major determinants of high-frequency neuronal firing. Functional analysis of the Arg320His mutant channel showed a dominant-negative loss-of-function effect. Ten cases had pathogenic mutations in known PME-associated genes (NEU1, NHLRC1, AFG3L2, EPM2A, CLN6 and SERPINI1). Identification of mutations in PRNP, SACS and TBC1D24 expand their phenotypic spectra to PME. These findings provide insights into the molecular genetic basis of PME and show the role of de novo mutations in this disease entity.

Depression and anxiety in women with epilepsy during pregnancy and after delivery: a prospective population-based cohort study on frequency, risk factors, medication, and prognosis.

OBJECTIVE: To assess incidence, prevalence, risk factors, and prognosis of peripartum depression and anxiety in a prospective study of women with epilepsy. METHOD: Pregnancies in women with epilepsy (n=706) were compared to pregnancies in all women without epilepsy (n=106,511) including women with specified nonepileptic chronic diseases (n=8,372) in the Norwegian Mother and Child Cohort Study. The database was linked to the Medical Birth Registry of Norway. Depression and anxiety were assessed with validated questionnaires five times from the second trimester to 36 months after delivery. Blood was drawn for analysis of antiepileptic drug (AED) concentrations. RESULTS: Women with epilepsy more often had peripartum depression (26.7%) or anxiety (22.4%) than women without epilepsy (18.9% and 14.8%, respectively, p<0.001 for both comparisons) and women with other chronic diseases (23.1% and 18.4%, respectively, p=0.03 and 0.01). Women using AEDs during pregnancy were especially at risk regardless of AED type. The risk further increased with the use of multiple AEDs and with high doses and/or plasma levels. Risk factors associated with peripartum depression and/or anxiety in the epilepsy cohort were high seizure frequency, a history of physical and/or sexual abuse, adverse socioeconomic factors, previous loss of a child, AED use, unplanned pregnancy, and prepregnancy depression and/or anxiety. The recovery rate 3 years after delivery was lower for women with epilepsy with a history of depression/anxiety or physical/sexual abuse than for women without epilepsy. Depressed women with epilepsy were less frequently treated with antidepressive drugs during pregnancy than women without epilepsy. SIGNIFICANCE: Women with epilepsy frequently have depression and anxiety during and after pregnancy. Patients at risk should be identified before delivery as depressive symptoms could be undertreated in this group.

Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy.

The primary aim of this study was to assess the risks of fetal growth restriction and birth defects in children exposed prenatally to newer and older antiepileptic drugs, using an unselected epilepsy cohort. Deliveries recorded in the compulsory Medical Birth Registry of Norway 1999-2011 formed the study population. All 2,600 children exposed to antiepileptic drugs during pregnancy were compared to all 771,412 unexposed children born to women without epilepsy. Children of untreated mothers with epilepsy served as an internal control group. The main outcomes were small for gestational age birth weight and head circumference, and major congenital malformations. Children exposed to antiepileptic drugs had a moderate risk of growth restriction. Infants exposed to topiramate had a considerable risk of microcephaly (11.4 vs. 2.4 %; OR 4.8; CI 2.5-9.3) and small for gestational age birth weight (24.4 vs. 8.9 %; OR 3.1; 95 % CI 1.9-5.3). Carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, gabapentin, and pregabalin had low malformation rates, whereas topiramate tended to have an elevated malformation rate. Valproate monotherapy was associated with a significant risk of birth defects (6.3 vs. 2.9 %; OR 2.5; CI 1.6-3.8), and specifically with septal heart defects and hypospadias. For mothers using valproate, the presence of major birth defect in one child was associated with a markedly increased risk for the siblings (42.9 vs. 6.7 %; OR 10.4; CI 2.3-46.7). Children of untreated mothers with epilepsy had malformation risk similar to the reference group. In conclusion, topiramate was associated with a substantial risk of fetal growth restriction, and possibly an increased malformation rate. Other newer-generation antiepileptic drugs had a low malformation rate. Valproate monotherapy had a significant malformation risk, especially in repeated pregnancies.

Myoclonus-dystonia and epilepsy in a family with a novel epsilon-sarcoglycan mutation.

Seizures have been reported in two families with myoclonus-dystonia due to epsilon-sarcoglycan (SGCE) mutations. We report a Norwegian family with myoclonus-dystonia and epilepsy associated with a novel SGCE mutation. All six manifesting SGCE mutation carriers had myoclonus, and dystonia was present in two patients. Sequencing of the SGCE gene in the proband identified a novel frameshift c.372delG mutation that predicts the amino acid change [p.Lys125SerfsX7] and the formation of a premature stop codon. The mutation segregated with myoclonus-dystonia in the family. The typical motor symptoms were accompanied by generalized seizures in four of six affected mutation carriers. The seizure type included febrile, absence and generalized tonic-clonic seizures. One deceased patient with severe epilepsy and myoclonus could not be tested for the SGCE mutation. Seizures are rarely observed in myoclonus-dystonia patients with SGCE mutations, and may not be a part of the phenotype. The co-occurrence of seizures and myoclonus-dystonia suggests that they are both due to the same underlying SGCE mutation. However, with epilepsy being a relatively common disorder and lack of complete co-segregation in our and previous families, it is possible that some patients suffer from two different genetic disorders. The presence of seizures and EEG abnormalities should not be considered exclusion criteria for the diagnosis of myoclonus-dystonia.

Psychiatric comorbidity and social aspects in pregnant women with epilepsy - the Norwegian Mother and Child Cohort Study.

OBJECTIVE: The objective of this study was to investigate psychiatric disease and social aspects in young women with epilepsy before and during pregnancy. METHOD: The study included self-reported data from 106,935 pregnancies. RESULTS: Seven hundred eleven women reported having epilepsy, and 45.9% of them were using antiepileptic drugs (AEDs). Compared to the reference group, self-reported eating disorders and depression were increased in the untreated epilepsy group before pregnancy. Both AED-treated and untreated women with epilepsy reported higher depression scores as assessed by the Hopkins Symptom Checklist, and the Lifetime Major Depression scale was increased in AED-treated women. Antiepileptic drug treatment was linked to low income (27.4% vs. 18.4%, p<0.001) and no income (5.5% vs. 2.6%, p=0.001). Low educational level was associated with epilepsy in AED-treated and untreated women (50.5%, p<0.001 and 46.9%, p<0.001 vs. 32.2%), as was unemployment due to disability (7.9%, p<0.001 and 6.5%, p<0.001 vs. 1.5%) and single parenting (4.4%, p=0.016 and 4.5%, p=0.007 vs. 2.4%). No difference was found for smoking, alcohol use, or narcotic use. CONCLUSION: Symptoms of depression were associated with epilepsy both during and before pregnancy. Epilepsy was linked to eating disorders before pregnancy. Unemployment, single parenting, and low educational level were linked to epilepsy in young pregnant females. Efforts aiming at treatment and screening for psychiatric comorbidity in pregnant women with epilepsy are important in the follow-up of these patients.

Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy.

IMPORTANCE: Exposure to antiepileptic drugs during pregnancy is associated with adverse effects on psychomotor development. OBJECTIVES: To determine whether signs of impaired development appear already during the first months of life in children exposed prenatally to antiepileptic drugs, and to explore potential adverse effects of antiepileptic drug exposure through breastfeeding. DESIGN, SETTING, AND PARTICIPANTS: Mothers at 13 to 17 weeks of pregnancy were recruited in the population-based, prospective Norwegian Mother and Child Cohort Study from 1999 to 2009. The mothers reported on their child's motor and social skills, language, and behavior using items from standardized screening tools at 6 months (n = 78,744), 18 months (n = 61,351), and 36 months (n = 44,147) of age. The mothers also provided detailed information on breastfeeding during the first year. MAIN OUTCOMES AND MEASURES The risk of adverse development in children according to maternal or paternal epilepsy was estimated as the odds ratio with corresponding 95% confidence interval, adjusted for maternal age, parity, education, smoking, breastfeeding, depression/anxiety, folate supplementation, and congenital malformation in the child. RESULTS: At age 6 months, infants of mothers using antiepileptic drugs (n = 223) had a higher risk of impaired fine motor skills compared with the reference group (11.5% vs 4.8%, respectively; odds ratio = 2.1; 95% CI, 1.3-3.2). Use of multiple antiepileptic drugs compared with the reference group was associated with adverse outcome for both fine motor skills (25.0% vs 4.8%, respectively; odds ratio = 4.3; 95% CI, 2.0-9.1) and social skills (22.5% vs 10.2%, respectively; odds ratio = 2.6; 95% CI, 1.2-5.5). Continuous breastfeeding in children of women using antiepileptic drugs was associated with less impaired development at ages 6 and 18 months compared with those with no breastfeeding or breastfeeding for less than 6 months. At 36 months, prenatal antiepileptic drug exposure was associated with adverse development regardless of breastfeeding status during the first year. Children of women with epilepsy who did not use antiepileptic drugs and children of fathers with epilepsy had normal development at 6 months. CONCLUSIONS AND RELEVANCE: Prenatal exposure to antiepileptic drugs was associated with impaired fine motor skills already at age 6 months, especially when the child was exposed to multiple drugs. There were no harmful effects of breastfeeding. Women with epilepsy should be encouraged to breastfeed their children irrespective of antiepileptic drug treatment.