Increased rate of acute caesarean sections in women with epilepsy: results from the Oppland Perinatal Database in Norway.

BACKGROUND AND PURPOSE: Studies in women with epilepsy (WWE) regarding pregnancy and labour complications have disclosed contradictory results. Our purpose was to investigate whether WWE have a higher risk of acute caesarean section (CS) or pregnancy complications than women without epilepsy or women with other chronic diseases and, if we found a higher risk, to explore potential explanations. METHODS: The study used prospectively registered obstetric data from the Oppland Perinatal Database in the period 2001-2011, containing information on 18 244 births, including 110 singleton pregnancies in mothers with validated epilepsy. Data regarding epilepsy were collected retrospectively from medical records. RESULTS: Epilepsy was a significant risk factor for acute CS, breech presentation and low birth weight in offspring [odds ratio (OR), 1.93, 95% confidence interval (CI), 1.2-3.1; OR, 2.29, 95% CI, 1.2-4.6 and OR, 2.10, 95% CI, 1.0-4.2, respectively]. In multivariate logistic regression analysis, antiepileptic drug exposure was an independent risk factor for acute CS (OR, 2.00; 95% CI, 1.06-3.77) and polytherapy was a significant risk factor for breech presentation (OR, 5.37; 95% CI, 1.13-25.57). Seizure frequency during pregnancy had no influence on the complication rate. CONCLUSIONS: We found that WWE using antiepileptic drugs during pregnancy had increased rates of acute CS, breech presentation and low birth weight, and that seizure frequency during pregnancy did not influence the complication rate.

Favorable change of lipid profile after carbamazepine withdrawal.

OBJECTIVE: Patients treated with carbamazepine (CBZ) have increased serum levels of total cholesterol (TC), high-density lipoproteins (HDL), and low-density lipoproteins (LDL). We aimed to investigate whether these changes of serum lipids are reversible after CBZ withdrawal. MATERIAL AND METHODS: We used a prospective, randomized double-blinded design. A total of 160 patients who had been seizure free on anti-epileptic drug monotherapy for more than 2 years were included and randomized to withdrawal or not. The intervention was completed by 150 (80 females, 53%) patients. Serum samples from before and 4 months after completed withdrawal or no withdrawal were obtained from 130 patients (63 females, 48%). Of these, 84 were treated with CBZ, 28 with valproate, nine with phenytoin, four with phenobarbital, and five with lamotrigine. Of the patients who had been treated with CBZ, 47 were randomized to the withdrawal group, and 37 were randomized to the non-withdrawal group. RESULTS: Among the CBZ-treated patients, a significant decrease in serum levels of TC, LDL, and apolipoprotein B (ApoB) were found in the withdrawal group compared with the non-withdrawal group. Mean differences in change were as follows: TC 0.68 mmol/l (P = 0.005, CL - 1.15 to -0.21); LDL - 0.67 mmol/l (P = 0.001, CL - 1.03 to -0.29); ApoB - 0.13 g/l (P = 0.02, CL - 0.23 to -0.03). No significant changes in HDL, apolipoprotein A, and C-reactive protein were detected. CONCLUSION: Our results indicate that CBZ may have unfavorable effects on serum levels of TC, LDL, and ApoB. However, these changes seem to be reversible even after years of treatment.

Repeated neuropsychological assessment in well-controlled epilepsy.

BACKGROUND: The majority of patients with epilepsy are seizure-free, and repeated neuropsychological assessment may be highly relevant in this group. However, previous studies have not addressed the possible influence of important clinical variables on repeated neuropsychological assessment in this population. METHODS: Using data from a large antiepileptic drug (AED) withdrawal study, we calculated the neuropsychological practice effects for 139 seizure-free patients with epilepsy and analysed the influence of different epilepsy-related factors on improvement that were observable 7 months after the initial neuropsychological assessment. RESULTS: A clear and significant improvement in neuropsychological test performance was found for all the tests employed, regardless of AED withdrawal. Furthermore, patients characterized by evidence of brain pathology, such as known cerebral aetiology, pathological MRI and pathological EEG, showed less practice effects than patients not characterized by these variables. The differences were primarily evident for measures of verbal learning and memory. CONCLUSION: The data obtained from this study suggest that the development of general norms for change in the particular patient population, as well as specific norms for change related to important clinical variables, might be necessary to be able to determine whether genuine neuropsychological changes have occurred in individual patients in this group.

Dravet syndrome--considerable delay in making the diagnosis.

OBJECTIVES: To assess delay in diagnosis and clinical characteristics of Dravet syndrome based on the Dravet register at The National Centre for Epilepsy in Norway. MATERIAL AND METHODS: Medical records of patients diagnosed with Dravet syndrome since 2007 were analysed. RESULTS: Twenty-two patients were identified. In 15, genetic screening disclosed mutations/deletions in the SCN1A gene. Average time from seizure onset to diagnosis was 7.4 years. Mean age at seizure onset was 6.7 months, nine had hemiconvulsions and 13 had generalized tonic-clonic seizures. The seizures were precipitated by fever in 17, by external heating in three. During second year of life, multiple seizure types and cognitive and motoric stagnation occurred. No patients became seizure-free with antiepileptic drugs. The effect of vagal nerve stimulation was disappointing. CONCLUSIONS: By making an early diagnosis, an extensive presurgical evaluation may be avoided, and the patient and their parents may be offered genetic guidance.

Gender differences in risk-taking behaviour in youth with epilepsy: a Norwegian population-based study.

OBJECTIVES: It is well known that behavioural problems and psychiatric disorders occur with greater prevalence in children and adolescents with epilepsy. Youth with epilepsy (YWE) may also be more susceptible to risk-taking behaviour, but this has seldom been studied. The aim of this study was to explore risk-taking behaviour in YWE. MATERIAL AND METHODS: In this study, 19,995 young people (age range: 13-19 years) participated and completed an extensive questionnaire, including The Strengths and Difficulties Questionnaire self-report. A variable, risk-taking behaviour, was identified, including daily consumption of alcohol, substance abuse or having committed a criminal offence such as being in a fight with a weapon, committing a burglary or using threats to obtain money. RESULTS: Two hundred and forty-seven youths reported currently having, or having had, epilepsy (lifetime prevalence: 1.2%). Of these, 8.3% reported daily alcohol consumption (1.0% in controls; P<0.001), 12.4% had tried illegal substances (5.5% of controls; P<0.001), and 19.7% had committed criminal offences (8.5% in controls; P<0.001). A gender difference was found: girls with epilepsy did not exhibit risk-taking behaviour more frequently than controls, but having epilepsy was a risk factor for such behaviour in boys (OR: 3.2). CONCLUSION: Boys with epilepsy exhibit risk-taking behaviour more frequently than controls. Other risk factors for this behaviour were living with a single parent, low family income and psychiatric symptoms. This behavioural association should be addressed as it probably contributes to the negative social outcomes that frequently occur in the adult epilepsy population.

Buccal midazolam or rectal diazepam for treatment of residential adult patients with serial seizures or status epilepticus.

OBJECTIVES: To compare the efficacy and tolerability of buccal midazolam with rectal diazepam as emergency treatment in residential adults with convulsive or non-convulsive serial seizures or status epilepticus (SE), and ascertain the preference between the two treatment options among the patients and the nursing staff. MATERIALS AND METHODS: The nursing staff of our residential epilepsy centre treated 80 episodes of serial seizures or SE lasting more than 5 min alternating with rectal diazepam or buccal midazolam. The dose of each study drug was tailored individually. The primary outcome measure was defined as cessation of seizure activity within 10 min without seizure relapse within 2 h. RESULTS: Convulsive SE was treated promptly, after a mean of 6.2 min, and terminated faster with buccal midazolam than with rectal diazepam; i.e. after a mean of 2.8 vs 5.0 min, respectively (n = 0.012). The other subcategories of emergency situations were treated after a mean of 25.0 min, and the seizure activity ceased after a mean of 7.4 min in the diazepam group and 7.6 min in the midazolam group (NS). The success rate was 83.3% in the diazepam group and 74.4% in the midazolam group (NS). The difference was mostly due to slightly more seizure relapses during the first 2 h in the midazolam group. Both treatment options were well tolerated, temporary tiredness being the most frequently occurring adverse effect. All the nursing staff and six of the seven patients who gained experience with both treatment options favoured the buccal route. CONCLUSIONS: Buccal midazolam appeared to be at least as effective as rectal diazepam with little or no side effects. The buccal administration was easy to handle and socially more acceptable than the rectal route.

Improvement in verbal memory after withdrawal of carbamazepine and valproate in patients with well-controlled epilepsy: a randomized, double-blind study.

BACKGROUND: For most major antiepileptic drugs, neuropsychological side effects have been reported. Healthy volunteer studies have found that both carbamazepine and valproate impair aspects of verbal memory. OBJECTIVE: The aim of this study was to assess the effects of carbamazepine and valproate on verbal memory, in a well-controlled epilepsy population. METHODS: This was carried out with a randomized, double-blind and placebo-controlled study of anticonvulsant withdrawal in patients receiving monotherapy. RESULTS: In the carbamazepine group (n=92), withdrawal significantly improved recall after 30 min (P=0.03). In the valproate group (n=32), withdrawal significantly improved performance of immediate word span (P=0.04). CONCLUSIONS: Withdrawal was randomized to placebo, but the choice of medication was not randomized to placebo. This means that the shown differences in neuropsychological outcome cannot with full certainty be attributed to either antiepileptic drug. The improvement of memory, after both carbamazepine and valproate withdrawal, was slight, and the impact on daily life function is uncertain.

Acute postoperative seizures after epilepsy surgery - a long-term outcome predictor?

OBJECTIVES: The prognostic value of acute postoperative seizures (APS) after epilepsy surgery is much debated. This study evaluated APS, defined as seizures in the first week post-surgery, as a predictor of long-term seizure outcome, and investigated the utility of other potential outcome predictors. MATERIALS AND METHODS: Medical records of 48 patients with temporal and extra-temporal epilepsy surgery were studied. Forty patients had lesional surgery. All had at least 2 year postoperative follow-up. RESULTS: At 2 year follow-up, 25 patients (53%) were seizure free. Univariate analysis showed that APS (P = 0.048), using ≥ six AEDs prior to surgery (P = 0.03), pathological postoperative EEG (P = 0.043) and female gender (P = 0.012) were associated with seizure recurrence. CONCLUSIONS: Univariate analysis indicate that APS, a high number of AEDs used prior to surgery, and pathological postoperative EEG are possible predictors of seizure recurrence after epilepsy surgery. Only gender retained significance in the multivariate analysis.

Antiepileptic monotherapy significantly impairs normative scores on common tests of executive functions.

BACKGROUND: Understanding how antiepileptic (AED) monotherapy influences normative test scores is of importance in the clinic for correct interpretation of neuropsychological profiles. Previous studies have primarily reported minor influence on neuropsychological raw scores, and the clinical relevance of these findings is unclear. AIM OF THE STUDY: To obtain a clinical valid answer to this question, we analysed changes in T-scores after AED withdrawal in a large group of well-controlled epilepsy patients, for tests previously shown to be sensitive to AED withdrawal. METHODS: We report outcomes on measures of choice reaction time from the California Computerized Assessment Package, on the Controlled Oral Word Association Test and on the Stroop Color-Word Interference Test. RESULTS: Significantly improved T-scores were revealed after AED withdrawal on five of the six tests of executive functions with mean improvement of 5 T-scores. Comparable results were achieved in the subgroup taking carbamazepine, with a mean improvement of 6.2 T-scores. CONCLUSION: The present results suggest that T-scores for computerized tests of choice reaction time and tests of verbal fluency and response inhibition may be significantly impaired as a consequence of AED monotherapy, and that careful interpretation of these scores is required in diagnostic assessment of patients receiving AED monotherapy.

Changes in autonomic cardiac control in patients with epilepsy after discontinuation of antiepileptic drugs: a randomized controlled withdrawal study.

The aim of this study was to assess cardiac autonomic control in patients with epilepsy before and after withdrawal of antiepileptic drugs (AEDs). The study was prospective, randomized and double blinded. Spectral analysis of heart rate variability (HRV) in 24 h ECG-registration before and after withdrawal of AEDs was used to assess autonomic cardiac control. The assessment of HRV with spectral analysis was based on sinus rhythm and normal heart beats [normal to normal beat (NN)]. Thirty-nine patients had 24 h rhythms free from any ectopic beats both before and after intervention, and were included in the analysis. Significant differences were found in the withdrawal group: filtered RR intervals for all 5 min segments of the analysis; percentage of differences between adjacent filtered RR intervals that are greater than 50 ms for the whole analysis; very low frequency power; low frequency power and high frequency power. The results demonstrate that slow withdrawal of AEDs in seizure-free patients with epilepsy on drug mono-therapy resulted in an increase in both parasympathetic and sympathetic functions, indicative of increased power amongst patients following cessation of AED treatment. As low HRV has been associated with increased mortality in patients with other diseases, this increased HRV may be beneficial.

Incidence and predictors for post-stroke epilepsy. A prospective controlled trial. The Akershus stroke study.

The aim of the study was to assess the incidence and identify predictors for post-stroke epilepsy (PSE), in particular the possible influence of treatment in a stroke unit (SU). Patients with PSE were identified between 4 weeks and 1 year after the stroke. Different parameters were studied as possible predictors. Twelve patients (2.5%) developed PSE during 12 months. Four of the patients (33%) were treated in an SU and eight of the patients (67%) were treated in general medical wards (GMWs) (P=0.50). Mean age in those with PSE was 75 and 76 in those without (P=0.57). Four out of 363 patients (1.1%) with minor stroke [Scandinavian Stroke Scale (SSS)-score >30] developed PSE. Seven out of 104 patients (6.3%) with severe stroke developed PSE (P=0.004). In the multivariate analysis SSS-score scores below 30 was a significant predictor for incidence of PSE (odds ratio=6.1, P=0.003). At 12 months the incidence of PSE was 2.5%. SSS-score below 30 was a significant predictor for PSE, whilst age and treatment in SU versus GMW were not.

Properties of the 15D and EQ-5D utility measures in a community sample of people with epilepsy.

To perform economic evaluation studies in epilepsy using utilities, such as cost-utility analyses, it is necessary to have reliable and valid instruments for eliciting people's preferences. The objective of this study was to assess the reliability and validity of two multiattribute utility measures in a community sample of 397 people with epilepsy. We assessed the test-retest reliability of individual questionnaire items and aggregate scores. Additionally, construct validity was assessed by correlating items of the EQ-5D with items of the 15D health status questionnaire, and discriminant validity was assessed by comparing scores for known groups. The test-retest reliabilities for the individual items of the 15D (weighted kappa 0.59-0.90, except mobility with only 0.28) and the EQ-5D (weighted kappa 0.49-0.86) were acceptable. For the composite utility scores the test-retest reliability was better (intraclass correlation coefficient 0.93 for both 15D and the EQ-5D). Spearman's rank correlations between EQ-5D single item scores and corresponding 15D single item scores were high (rho 0.34-0.79) and generally higher than the associations between non-corresponding items. Some EQ-5D and 15D items discriminated well between patients according to seizure status, psychiatric comorbidity and working status; less well after antiepileptic drug use and neurologic comorbidity. Both the EQ-5D and 15D were reliable instruments and showed properties supporting the construct validity of both measures.

Reliability and validity of a Norwegian version of the quality of life in epilepsy inventory (QOLIE-89).

PURPOSE: To develop a Norwegian version of the Quality of Life in Epilepsy Inventory (QOLIE-89) and to confirm its psychometric properties. METHODS: The QOLIE-89 was adapted to Norwegian language through a translation-backtranslation procedure. The assessment included 397 patients with epilepsy. We assessed internal consistency and test-retest reliabilities. Construct validity was assessed by correlating scales with items of the 15D health status questionnaire, and discriminant validity was assessed by comparing scores for known groups. RESULTS: The internal consistency reliability (Cronbach's alpha, 0.76-0.92) and test-retest reliability (intraclass correlation coefficient, 0.67-0.96) for the individual domains were acceptable. Spearman's rank correlations between QOLIE-89 domain scores and corresponding 15D single-item scores were high (p, 0.47-0.76), and generally higher than the associations between noncorresponding items. Most QOLIE-89 items discriminated well between patients according to seizure status, psychiatric comorbidity, and working status; less well after antiepileptic drug use and neurologic comorbidity. CONCLUSIONS: In this cross-sectional survey, the Norwegian version of the QOLIE-89 was reliable and showed properties supporting construct validity, at a level comparable with the original U.S. version.

The health-related quality of life of patients with epilepsy compared with angina pectoris, rheumatoid arthritis, asthma and chronic obstructive pulmonary disease.

The objective of this study was to compare the health-related quality of life (HRQL) of patients with epilepsy with populations suffering from different chronic diseases, using the short form 36 (SF-36) health profile measure. The populations to be compared were adult patients drawn from hospital based registers, with confirmed epilepsy (n = 397), angina pectoris (n = 785), rheumatoid arthritis (n = 1,030), asthma (n = 117) and chronic obstructive pulmonary disease (COPD) (n = 221). Health-related quality of life scores were compared using analysis of covariance (ANCOVA) for predicting mean scores adjusted for age, gender, education and comorbidity. Patients with epilepsy on average scored highest on all scales, reflecting that in our sample the majority had well-controlled epilepsy. Our results indicate that the HRQL of a representative sample of patients with epilepsy is good, when compared with other chronic disorders, although reduced in several dimensions compared with a general reference population. Patients with rheumatoid arthritis (RA) and COPD scored lowest on the physical function scales, while rheumatoid arthritis patients reported most pain.

Predictors for recurrence of epileptic seizures in a general epilepsy population.

The aim of our study was to identify predictors for recurrence of epileptic seizures in a large county hospital population. We identified 956 patients (18-67 years) with ICD 9 code 345 as primary diagnosis, seen at the Central Hospital of Akershus over 7 years (1987-1994). The diagnosis of epilepsy was confirmed for 696 of the patients. These were divided into two groups: (1) no seizures during the previous year (n = 485) and (2) seizures during the previous year (n = 184). To identify predictors for recurrence of seizures, we used neurologic deficit, number of AEDs used, CT-scan findings, EEG findings, aetiology, gender, age below and above 50 years and comorbidity as independent variables in a logistic regression model. In a univariate analysis, the strongest predictors for recurrence of seizures were: age above 50 years (OR = 5.2;P < 0.0001), known aetiology (OR = 1.4;P = 0.04) and use of two or more AEDs (OR = 5. 7;P < 0.0001). In the multivariate analysis age, more than 50 years (OR = 1.7;P = 0.0216) and use of two or more AEDs (OR = 5.6;P < 0.0001) were the only predictors for recurrence of epileptic seizures.