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.

Discrepancies between physicians' prescriptions and patients' use of antiepileptic drugs.

OBJECTIVES: The purpose of this study was to investigate whether prescribed antiepileptic drugs (AEDs) were consistent with what patients actually used, and to explore challenges in treatment and reasons for possible discrepancies according to patients' view of their medication. MATERIAL AND METHODS: Anonymized data were collected from a questionnaire distributed to in- and outpatients and their physicians at the National Center for Epilepsy, Norway. They were asked to report AEDs and dosages currently used. Additionally, 20 patients were interviewed regarding AED treatment. This information was analyzed qualitatively. RESULTS: Answers from 174 patients and their physicians were analyzed. The patients' mean age was 43 years (21-83 years), 85 (49%) were women, and 56% used AED polytherapy (2-5 AEDs). For 56 patients (32%), there was a discrepancy regarding either dosage (n = 70) or prescribed drug (n = 32) (12%). There were discrepancies for all top 10 used drugs, with a similar distribution of patients stating lower or higher doses. Based upon interviews of 20 patients, concerns and challenges in AED treatment were addressed. Polytherapy and adverse effects which reduced the patients' quality of life were the most important obstacles for adherence to the treatment. CONCLUSIONS: This study revealed that 32% of the patients had one or more discrepancies between what the physician had prescribed and what the patients actually used, in either the type or the dosages of AEDs. Polytherapy, adverse effects, and poor adherence were common challenges. Improved communication and information about AEDs may improve adherence and thus treatment outcome.

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.

Retention rate of zonisamide in intractable epilepsy.

OBJECTIVES: To assess the effect and tolerability of zonisamide (ZNS) as adjunctive treatment for difficult-to-treat epilepsy in adult Scandinavian patients. MATERIAL AND METHODS: 151 outpatients (mean age: 42.5 years) from 18 centres in Denmark, Sweden and Norway were recruited to the study. 81.5% had focal epilepsy, and the mean number of previously tried AEDs was 4.5. The patients were given ZNS as add-on treatment, and the ZNS dosing and the visit frequency were governed by the treating physician. The primary efficacy endpoint was the retention rate after 12-month treatment. Assessments included also responder rate, type and frequency of adverse events, healthcare resource utilization (HCRU) and quality of life (QOLIE-31). RESULTS: 90 patients (59.6%) completed the study. Mean daily ZNS dose was 300.8 mg. After 12 months, 81 patients were still on ZNS, that is a retention rate of 53.6%. The mean reduction of seizure frequency at 12 months was 27%. Best effect was seen in those with focal and those with secondary generalized seizures. In the QOLIE-31, there was a mean increase from baseline of 4.8 points. The tolerability was generally good. The majority of side effects were CNS-related, dizziness, fatigue, seizure aggravation, and headache being most prevalent. 21.2% had adverse events leading to withdrawal of ZNS. CONCLUSIONS: A retention rate of 53.6% after 1 year of treatment with ZNS is roughly in accordance with the retention rates found for lamotrigine, oxcarbazepine, levetiracetam and topiramate in drug-resistant patients.

Modified Atkins diet may reduce serum concentrations of antiepileptic drugs.

BACKGROUND: Modified Atkins diet is a treatment option for patients with pharmacoresistant epilepsy that is not suitable for surgery. In the last few years, we have tried dietary treatment added to antiepileptic drugs (AEDs) in adult patients with severe epilepsy. AIM OF THE STUDY: To examine a possible pharmacokinetic interaction between the modified Atkins diet and AEDs. METHODS: In four patients, AED serum concentrations were measured before onset and after 4 and 12 weeks on the diet. The patients used combinations of two or three AEDs, including carbamazepine, clobazam, lamotrigine, nitrazepam, oxcarbazepine, valproate, zonisamide, and topiramate. The patients did not change the type or dose of their AEDs during the diet period. RESULTS: After 12 weeks on the diet, the average serum concentrations of the respective AEDs were reduced by 35% (range 6-46%) compared to prediet values. CONCLUSIONS: Modified Atkins diet used as add-on therapy to AEDs in four patients with drug resistant seizures caused a considerable decrease in AED serum concentrations. In individual patients, this could be of clinical relevance, and we recommend that AED serum concentrations should be closely monitored when offering this diet to adults with epilepsy.

Multiple sclerosis and seizures: incidence and prevalence over 40 years.

OBJECTIVES: The prevalence of multiple sclerosis (MS) is increasing worldwide. Epileptic seizures are more common in MS patients than in the general population. The aim of this study was to investigate changes in the prevalence and incidence of MS in a well-defined population over several decades and estimate the occurrence of epilepsy in the same cohort. MATERIALS AND METHODS: Patients diagnosed with MS in the County of Vestfold, Norway in the period of 1983-2003 were identified. Point prevalence for MS and epilepsy was calculated for January 1, 2003. The average annual incidence rates were calculated in five-year periods from 1983 to 2002. These numbers were compared to previously published figures of prevalence from 1963 and incidence from 1953. RESULTS: On prevalence day, we identified 364 patients diagnosed with MS living in Vestfold. Thus, the prevalence increased from 61.6/100,000 in 1963 to 166.8/100,000 in 2003. In the period 1983-2002, the annual incidence fluctuated between 4.2 and 7.3/100,000/year (mean 4.5, 95% CI 3.6 - 5.5). In 2003, the portion of MS patients with epileptic seizures was 7.4%, compared to 2.9% in 1963. CONCLUSIONS: During the 40 years follow-up of this population, the incidence of MS was stable, while the prevalence of MS and the share of MS patients with epileptic seizures increased. Compared to the general population, the risk of having active epilepsy was increased fourfold. We assume that this is a consequence of an increased survival in MS patients.

Long-term outcome of resective epilepsy surgery in Norwegian children.

AIM: The aim of this study was to evaluate the long-term results of resective surgery on children with difficult-to-treat epilepsy in Norway. METHODS: In the period 1995-2004, 64 surgical procedures (54 resections and 10 functional hemispherotomies) were performed in 54 children. The children's medical records were retrospectively reviewed at a minimum of 2 years after surgery. We sent a questionnaire regarding their epilepsy (seizures, usage of antiepileptic drugs) and general functioning (social situation, motor, language, cognition, behavioural or emotional problems, any remedial action) to the children/parents after a mean follow-up period of 7 years. RESULTS: 55.5% of the children were seizure-free. The success rate varied according to the type of surgery. Best results were found after functional hemispherotomies and temporal lobe resections, as nine of 10 (90%) and 10 of 19 (53%) of these patients, respectively, became seizure-free. In addition to a better seizure control, 71% of the children/parents reported of a better cognitive and psychosocial functioning. CONCLUSION: The results of epilepsy surgery in this paediatric cohort are very edifying, and it is our impression that this treatment option is underused in Norway.

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.

Bone health in adults with epilepsy.

Patients with epilepsy have a 2-6 times greater risk of bone fractures compared with the general population. There are several potential explanations. Some fractures are caused by seizure-related injuries, or they may be associated with the osteopenic effect of reduced physical activity in patients with epilepsy. Antiepileptic drugs (AEDs), especially those that affect the liver enzymes, e.g., phenytoin, carbamazepine, phenobarbital, as well as valproate, are also associated with increased fracture rate and low bone mineral density. Many patients with epilepsy and general practitioners seem unaware of this problem. Measurements of bone density should be taken regularly in patients at risk of developing osteoporosis. Non-pharmaceutical initiatives, such as partaking in regular physical activity and eating a well-balanced diet, should be recommended. The risk of developing osteoporosis should be taken into consideration in the selection of an AED for treating a newly diagnosed patient with epilepsy.

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.

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.

Psychiatric comorbidity and use of psychotropic drugs in epilepsy patients.

OBJECTIVES: Although epilepsy is associated with a high rate of psychiatric comorbidity, clinicians may withhold treatment with psychotropic drugs for fear of worsening seizures. We have assessed the occurrence of psychiatric disorders in a cohort of epilepsy patients and used the results to discuss this important topic. MATERIAL AND METHODS: Based on a questionnaire we made a survey of psychiatric symptoms in 167 adult patients referred to a tertial epilepsy center. The mean age was 42 years, and 72% had active epilepsy. RESULTS: Forty three patients (26%) had a psychiatric disorder, and 22 patients (13%) used psychotropic drugs. The most frequent diagnoses were mood disorders and anxiety. CONCLUSIONS: Compared with the general population, people with epilepsy have an increased risk of developing psychiatric disorders. Patients with uncontrolled seizures are most vulnerable. These disorders appear to be under-diagnosed and under-treated, and the fear that psychotropic drugs can cause seizure exacerbation is probably overstated.

Epilepsy and driving: considerations on how eligibility should be decided.

Although few neurologists are formally trained in traffic medicine, they are frequently asked to assess whether a patient is medically fit to drive. For patients with epilepsy, the physician must assess the risk of the patient having a seizure while driving, and decide what is an acceptable risk. The legislation on this subject is aiming at finding a reasonable balance between two important considerations: public safety and a patient's individual need to drive. For the neurologist to explain and put into practice the legislation may be a demanding task and a challenge to the doctor-patient alliance. The decision on driving capability should be tailored to the individual patient and based on careful evaluation and informed judgement. In Norway, to qualify for a driver's license, a seizure-free interval of at least 12 months is currently required for group 1 drivers (passenger cars), whereas group 2 drivers (heavy motor vehicles, commercial driving) must have been seizure-free for at least 10 years and not have experienced epileptic seizures from the age of 18 years. Norwegian physicians are obliged to report patients with seizures to driving authorities, although this is an unpopular rule. In reviewing the available literature, it is apparent that despite there being relatively few sound studies, the risks of car accidents among persons with epilepsy may previously have been overestimated.

The occurrence and characteristics of auras in a large epilepsy cohort.

OBJECTIVES: Despite several studies, estimates of the frequency with which auras occur in conjunction with epilepsy continue to be imprecise. The aim of this study was to assess the occurrence and characteristics of auras in a large population-based epilepsy cohort. MATERIALS AND METHODS: Subjects with verified epilepsy were recruited from population-based twin registries in the USA, Denmark and Norway. Using a structured interview in which a list of auras was provided, subjects were asked about the warning symptoms preceding their epileptic attacks. RESULTS: 31% of the total sample (n = 1897) and 39% of those with active epilepsy (n = 765) had experienced an aura. Six percent reported more than one type. Non-specified auras were most frequently reported (35%), followed by somatosensory (11%) and vertiginous (11%). While the majority of those reporting auras (59%) had focal epilepsies, auras of a mostly non-specific nature were experienced by 13% of those with generalized epilepsies. CONCLUSION: Auras serve an important purpose in that they may prevent seizure-related injuries and could provide an indication as to where the seizures originate. The occurrence of auras often is underestimated, especially in children and those with learning disabilities.

Genetic screening of Scandinavian families with febrile seizures and epilepsy or GEFS+.

BACKGROUND: Mutations in the three genes SCN1A, SCN1B and GABRG2, all encoding subunits of ion channels, have been known to cause generalized epilepsy with febrile seizures plus (GEFS+) in families of different origin. OBJECTIVE: To study the occurrence of mutations in these genes in families with GEFS+ or a GEFS+ resembling phenotype of Scandinavian origin. MATERIAL AND METHODS: We performed linkage analysis in 19 Scandinavian families with a history of febrile seizures (FS) and epilepsy or GEFS+. Where linkage could not be excluded, the genes of interest were sequenced. RESULTS: We identified only one mutation in SCN1A, which seems to be a rare variant with no functional consequence. CONCLUSION: This suggests that mutations in these three genes are not a prevalent cause of familial cases of FS and epilepsy or GEFS+ in Scandinavia.

Age-specific prevalence of epilepsy in Oppland County, Norway.

OBJECTIVE - To assess the prevalence of epilepsy in Oppland County, Norway, particularly with respect to age. MATERIALS AND METHODS - Population-based and hospital-based approaches were used to identify individuals with active epilepsy born in 1925, 1940, 1955, 1960 and 1970. Cases with active epilepsy were defined as individuals who had experienced more than one epileptic seizure during the last 5 years and/or were taking antiepileptic drugs. RESULTS - From a population of 11,089 persons, 90 individuals were identified with active epilepsy. The age-distributed prevalence (cases per 1000 individuals born in a specified year) of active epilepsy was 10.2 for those born in 1925, 11.1 for those born in 1940, 4.5 for those born in 1955, 7.5 for those born in 1960 and 9.4 for those born in 1970. Mean epilepsy prevalence was estimated to be 8.2 cases/1000 inhabitants. CONCLUSIONS - An epilepsy prevalence of 8.2 cases/1000 inhabitants is in accordance with the results of similar studies from the western world. However, the results of such studies will vary according to the definition of 'active epilepsy'. By using the narrower International League Against Epilepsy's definition, the prevalence in our study is reduced to 5.3 cases/1000 inhabitants.

Coeliac disease, unilateral occipital calcifications, and drug-resistant epilepsy: successful lesionectomy.

PURPOSE: To draw attention to the triad of coeliac disease (CD), occipital calcifications, and drug-resistant epilepsy, with focus on the outcome of epilepsy surgery. METHODS: We describe a male patient who despite a diagnosis of CD from the age of 9 did not comply with the gluten-free diet. At the age of 11 he developed simple and complex partial seizures with visual symptoms, anxiety, and ambulatory automatisms. His epilepsy appeared to be drug resistant, and after having tried nine antiepileptic drugs (AEDs), alone or in combinations, he underwent a presurgical evaluation at the age of 30. Interictal standard electroencephalograms (EEGs) disclosed frequent biparieto-occipital epileptiform discharges. Computed tomography showed cortical-subcortical punctate calcifications in the right parieto-occipital region, where his seizures seemed to start, according to ictal EEG registrations from intracranial strip electrodes. RESULTS: At the age of 31 he underwent epilepsy surgery. A 5 x 6 cm large area of the right parieto-occipital region was resected, including the area with calcifications. Except for a few short-lasting episodes of anxiety (simple partial seizures?) he has now been seizure-free for 12 years. AEDs were withdrawn 5 years ago. Postoperatively he was left with an upper left-sided quadrant anopsia, which is not bothering him. CONCLUSIONS: In patients with CD, unilateral occipital calcifications, and drug-resistant epilepsy, epilepsy surgery should be considered, as a lesionectomy might be very successful.

The ideal characteristics of antiepileptic therapy: an overview of old and new AEDs.

New and improved anti-epileptic drugs (AEDs) have made the concept of choice, according to the individual prognosis and probable response to specific regimens, increasingly feasible. Inter-individual variability in syndrome severity and complexity make individualization necessary. We propose three categories of disorder control according to the individual objectives of the patient: (1) seizure control, (2) epilepsy control and ultimately, (3) "epilepsy cure"; the latter remaining a largely idealistic target today. An AED is likely to be successful if it exhibits "optimal" characteristics, such as drug efficacy, tolerability, pharmacokinetics, interactions and cost-effectiveness. This review discusses the "optimal" characteristics of add-on AEDs, which, in addition to seizure control, will contribute to the achievement of epilepsy control and therefore address the currently unmet clinical needs of epilepsy treatment.

[Chronic intermittent vagal nerve stimulation--a new therapeutic approach in epilepsy]. / Kronisk intermitterende stimulering av nervus vagus--en ny behandlingsform ved epilepsi.

BACKGROUND: Vagal nerve stimulation is a new non-pharmacological therapy for patients with refractory epilepsy. Introduced in USA in 1988, the treatment is based on animal experiments demonstrating that intermittent stimulation of the vagal nerve could prevent or reduce the frequency and/or duration of seizures. MATERIAL AND METHODS: At the National Hospital in Norway, 47 therapy-resistant patients have had a vagal nerve stimulator implanted since June 1993. We have used the Neuro-Cybernetic Prosthesis system from Cyberonics, consisting of a programmable pulse generator, a bipolar vagal nerve stimulator lead, a programming wand with accompanying software, and a hand-held magnet. The mean age of the population was 34.4 years (12-70 years). All had a long-standing epilepsy with frequent seizures, 36 (77%) had seizures every day. The majority (89%) had localization-related epilepsy. Mean follow-up time was 2.7 years (0.4-6.5 years). RESULTS: 16 patients (34%) responded to the treatment with > 50% reduction in seizure frequency. No one, however, became seizure free. 20 patients (43%) had no seizure reduction. 24 of the patients (51%) benefited from extra stimulation triggered by the magnet. The stimulation affected several types of seizures; most often a reduction in frequency of secondary generalised tonic-clonic seizures was noted. Hoarseness, coughing and a tingling sensation in the throat were the most frequently reported side effects occurring during stimulation. The patients tended to habituate to these side effects. In 14 patients (30%), the device has been explanted, mostly due to lack of efficacy. INTERPRETATION: Considering the fact that this patient group belongs to the most refractory part of the epilepsy population, the results are regarded as promising and they are in keeping with results from other studies. However, the role of vagal nerve stimulation in the future treatment of epilepsy is still not settled. Several questions remain unanswered, e.g. what are the exact mechanisms of action behind the seizure reducing effect, and which patients are most suitable for this treatment?