Long-term adjunctive lacosamide treatment in patients with partial-onset seizures.

OBJECTIVE: To evaluate long-term (up to 5.5 years) safety, seizure reduction, and maintenance of efficacy of the antiepileptic drug (AED) lacosamide as adjunctive treatment in an open-label extension trial (SP774; ClinicalTrials.gov: NCT00515619). METHODS: Three hundred and seventy-six adults with partial-onset seizures taking 1-3 AEDs enrolled following completion of a double-blind trial of adjunctive lacosamide. During open-label treatment, dosage of lacosamide (100-800 mg/day) and/or concomitant AEDs could be adjusted to optimize tolerability and seizure control. RESULTS: Kaplan-Meier estimates of patient retention were 74.5% at 12 months, 52.9% at 36 months, and 40.6% at 60 months; median open-label treatment duration was 1183 days (~3.2 years). The most frequently reported treatment-emergent adverse events were dizziness (24.2%), headache (14.4%), diplopia (13.8%), and nasopharyngitis (13.8%); 9.0% of patients discontinued due to adverse events, most commonly dizziness (1.3%). Median percent reduction in 28-day seizure frequency from baseline of the double-blind trial was 49.9% overall, 55.4% for 1-year completers, and 62.3% for 3-year completers. Overall, 50.0% of patients were considered ≥50% responders (achieved ≥50% reduction in 28-day seizure frequency); 55.9% of 1-year completers and 63.0% of 3-year completers were ≥50% responders. CONCLUSION: In eligible patients who entered the open-label extension trial, lacosamide was generally well tolerated. For most patients within each yearly completer cohort, seizure reduction was maintained over time.

The bacterial-type [4Fe-4S] ferredoxin 7 has a regulatory function under photooxidative stress conditions in the cyanobacterium Synechocystis sp. PCC 6803.

Ferredoxins function as electron carrier in a wide range of metabolic and regulatory reactions. It is not clear yet, whether the multiplicity of ferredoxin proteins is also reflected in functional multiplicity in photosynthetic organisms. We addressed the biological function of the bacterial-type ferredoxin, Fed7 in the cyanobacterium Synechocystis sp. PCC 6803. The expression of fed7 is induced under low CO2 conditions and further enhanced by additional high light treatment. These conditions are considered as promoting photooxidative stress, and prompted us to investigate the biological function of Fed7 under these conditions. Loss of Fed7 did not inhibit growth of the mutant strain Δfed7 but significantly modulated photosynthesis parameters when the mutant was grown under low CO2 and high light conditions. Characteristics of the Δfed7 mutant included elevated chlorophyll and photosystem I levels as well as reduced abundance and activity of photosystem II. Transcriptional profiling of the mutant under low CO2 conditions demonstrated changes in gene regulation of the carbon concentrating mechanism and photoprotective mechanisms such as the Flv2/4 electron valve, the PSII dimer stabilizing protein Sll0218, and chlorophyll biosynthesis. We conclude that the function of Fed7 is connected to coping with photooxidative stress, possibly by constituting a redox-responsive regulatory element in photoprotection. In photosynthetic eukaryotes domains homologous to Fed7 are exclusively found in chloroplast DnaJ-like proteins that are likely involved in remodeling of regulator protein complexes. It is conceivable that the regulatory function of Fed7 evolved in cyanobacteria and was recruited by Viridiplantae as the controller for the chloroplast DnaJ-like proteins.

Virtual reality simulator training of laparoscopic cholecystectomies - a systematic review.

BACKGROUND AND AIMS: Simulators are widely used in occupations where practice in authentic environments would involve high human or economic risks. Surgical procedures can be simulated by increasingly complex and expensive techniques. This review gives an update on computer-based virtual reality (VR) simulators in training for laparoscopic cholecystectomies. MATERIALS AND METHODS: From leading databases (Medline, Cochrane, Embase), randomised or controlled trials and the latest systematic reviews were systematically searched and reviewed. Twelve randomised trials involving simulators were identified and analysed, as well as four controlled studies. Furthermore, seven studies comparing black boxes and simulators were included. RESULTS: The results indicated any kind of simulator training (black box, VR) to be beneficial at novice level. After VR training, novice surgeons seemed to be able to perform their first live cholecystectomies with fewer errors, and in one trial the positive effect remained during the first ten cholecystectomies. No clinical follow-up data were found. Optimal learning requires skills training to be conducted as part of a systematic training program. No data on the cost-benefit of simulators were found, the price of a VR simulator begins at EUR 60 000. CONCLUSIONS: Theoretical background to learning and limited research data support the use of simulators in the early phases of surgical training. The cost of buying and using simulators is justified if the risk of injuries and complications to patients can be reduced. Developing surgical skills requires repeated training. In order to achieve optimal learning a validated training program is needed.

Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy.

OBJECTIVE: To compare the cognitive effects of lamotrigine vs topiramate as adjunctive therapy in adults with epilepsy. METHODS: A multicenter, double-blind, randomized, prospective study was conducted in adults with partial seizures. Lamotrigine or topiramate was introduced as an adjunctive therapy to carbamazepine or phenytoin and titrated over 8 weeks to target doses. These drugs were maintained another 8 weeks (maintenance phase) without dosage changes. The primary endpoint was change from screening to the end of the maintenance phase in a combined analysis of standardized measures of cognition (Controlled Oral Word Association Task [COWA]; Stroop Color-Word Interference; Digit Cancellation; Lafayette Grooved Pegboard, dominant hand; Rey Auditory Verbal Learning Test, delayed recall; and Symbol-Digit Modalities test). RESULTS: For the primary endpoint, cognitive performance at the end of the maintenance phase was better with lamotrigine than with topiramate (415.3 vs 315.1; p < 0.001). On the individual cognitive tests, performance was better with lamotrigine than with topiramate in mean changes from screening on the COWA (p < 0.001), Stroop Color-Word Interference (p = 0.038), and Symbol-Digit Modalities tests (p < 0.001). The treatment effect exceeded the minimum clinically important difference for the COWA and the Symbol-Digit Modalities test. Mean changes from screening in the Performance-On-Line test simulating driving skills reflected better performance with lamotrigine than with topiramate (p = 0.021). The median percentage change from baseline in seizure frequency was lower with lamotrigine than with topiramate during the escalation phase (-80% vs -100%; p = 0.028) but not during the maintenance phase (-75% vs -100%; p = 0.062). The frequencies of cognitive adverse events and of premature withdrawals related to cognitive decline were higher with topiramate than with lamotrigine (6% vs 0%; p = 0.013). CONCLUSION: Lamotrigine had significantly less impact than topiramate on measures of cognition when used as adjunctive therapy for partial seizures.

Antiepileptic drug use and birth rate in patients with epilepsy--a population-based cohort study in Finland.

BACKGROUND: Antiepileptic medication use affects reproductive endocrine function, but its impact on fertility is not well known. METHODS: All epilepsy patients, who were approved as being eligible for reimbursement for antiepileptic drug (AED) costs from the Social Insurance Institution (SII) of Finland for the first time 1985-94, were identified from the SII database. A reference cohort without epilepsy was identified from the Finnish Population Register Centre. Information on AED purchases 1996-2000 was obtained from the SII database through computerized record linkage with the unique personal identification number assigned to all residents of Finland. The three AEDs included were carbamazepine, oxcarbazepine (OXC) and valproate. RESULTS: Birth rate was lower in both men and women with epilepsy on AEDs than in the reference cohort without epilepsy. However, compared with patients not using AED during the study period, the birth rate was lowered only among men on OXC [rate ratio (RR) = 0.52, 95% confidence interval (CI) = 0.32, 0.84]. CONCLUSIONS: The birth rate was lower in both women and men on any of the three AEDs compared with the reference cohort without epilepsy. However, a statistically significant difference between treated and untreated patients was only seen in men on OXC. It is unclear to what extent the differences found in this study are due to social or biological factors.

Suppressed circadian heart rate dynamics in temporal lobe epilepsy.

OBJECTIVES: To measure interictal circadian rhythm of heart rate (HR) variability in patients with temporal lobe epilepsy (TLE) using a 24 hour ECG recording. METHODS: Various conventional and dynamic fractal measures of HR variability were analysed in 17 patients with refractory TLE, 20 patients with well controlled TLE, and 37 healthy age and sex matched control subjects. RESULTS: The SD of all RR intervals (p < 0.01), the measured power spectral components of HR variability (low frequency power (p < 0.01), high frequency power (p < 0.05)), and the SD1 (p < 0.05) and SD2 (p < 0.01) Poincaré two dimensional vector analysis measurements were suppressed in the patients. This suppression was observed during both day and night time; however, it was more pronounced at night, and nocturnal increase in HR variability usually seen in the normal population could not be detected in the patients. The HR variability measures did not correlate with the duration of epilepsy, the age of the patients, or with the anti-epileptic drugs used. CONCLUSION: TLE was associated with reduced HR variability, which was more pronounced during night than day, and the nocturnal increase in HR variability was abolished in patients with TLE. The alteration in autonomic regulation of HR variability was similar in patients with both refractory and well controlled TLE.

Antiepileptic drug use of women with epilepsy and congenital malformations in offspring.

OBJECTIVE: To compare the risk for congenital malformations in offspring between women with epilepsy being treated with antiepileptic drugs (AEDs) during pregnancy and those who discontinued their antiepileptic medication before pregnancy in a population-based cohort of female patients with epilepsy. METHODS: All patients with epilepsy (n = 20,101) eligible for AED reimbursement for the first time during 1985 to 1994 were identified from the Social Insurance Institution of Finland. Information on births during 1991 to 2000 was obtained from the National Medical Birth Registry. Information on AED use during pregnancy and on pregnancy outcomes was abstracted from medical records. RESULTS: Congenital malformations were more common among offspring of women on antiepileptic medication (65/1,411; 4.6%) than among offspring of untreated patients (26/939; 2.8%) (p = 0.02). The risk of malformations was substantially higher in the offspring of patients using valproate as monotherapy (OR = 4.18; 95% CI: 2.31, 7.57) or valproate as polytherapy (OR = 3.54; 95% CI: 1.42, 8.11) than of untreated patients. Polytherapy without valproate was not associated with increased risk of malformations. CONCLUSION: Excess risk was confined to patients using valproate during pregnancy. The risk for malformations was not elevated in offspring of mothers using carbamazepine, oxcarbazepine, or phenytoin (as monotherapy or polytherapy without valproate).

Birth rate among patients with epilepsy: a nationwide population-based cohort study in Finland.

Few reports on population-based studies of birth rate among epilepsy patients have been published. In most previous studies, fertility has been lower among epilepsy patients than in the rest of the population. However, conflicting results have also been reported. Because of small samples and selective material, the generalizability of these results is also limited. The authors conducted a population-based cohort study of birth rate (1985-2001) in a nationwide Finnish cohort of patients with newly diagnosed epilepsy and a population-based reference cohort. All patients (n = 14,077) approved as eligible for reimbursement for antiepileptic medication from the Social Insurance Institution of Finland (KELA) for the first time between 1985 and 1994 were identified from the KELA database. A reference cohort (n = 29,828) was identified from the Finnish Population Register Center, with frequency-matching on age. Information on follow-up status and livebirths were also obtained from the Finnish Population Register Center. The birth rate was lower in patients with epilepsy than in the reference cohort among both men (hazard ratio = 0.58, 95% confidence interval: 0.54, 0.62) and women (hazard ratio = 0.88, 95% confidence interval: 0.83, 0.93). There were a clear decreasing trend by age at observation in men with epilepsy and a moderate decreasing trend by age at start of follow-up in women with epilepsy.

Anticardiolipin and antinuclear antibodies in epilepsy--a population-based cross-sectional study.

Increased prevalence of autoantibodies has been suggested in patients with epilepsy. This study determined the presence of autoantibodies in a representative cohort of 960 patients with epilepsy. The frequency of antinuclear antibodies (ANA), immunoglobulin G class anticardiolipin antibodies (aCL) and anti-B2-glycoprotein I antibodies were studied in 960 consenting adult patients with epilepsy and in 580 population-based reference subjects identified from the Finnish Population Registry. Overall the frequencies of the autoantibodies studied did not differ between patients with epilepsy and reference subjects. aCL were present in 4.5% of the patients and in 5.0% of the reference subjects and 17% of both the patients and the reference subjects had antinuclear antibodies. However, patients with partial epilepsy for > or =30 years were three times more likely to have aCL than patients with partial epilepsy for <10 years. Patients with partial epilepsy and > or=1 seizure per month were 2.2 times more likely to have aCL than patients with partial epilepsy with <1 seizure per month. Moreover, ANA tended to be more frequent among patients with > or =1 seizure per month. No association was found between the major antiepileptic drugs and autoantibodies. Overall the frequencies of the autoantobodies studied were similar in the large epilepsy cohort and in matched reference subjects from the general population. However, a long duration of epilepsy and poor seizure control were associated with an increased presence of aCL in patients with partial epilepsy.

Long-term reproductive endocrine health in young women with epilepsy during puberty.

OBJECTIVE: To evaluate the outcome of epilepsy and later reproductive endocrine health in girls who had epilepsy during puberty, using a population-based controlled study. METHODS: Sixty-nine patients (88%) and 51 control subjects (94%) of previously identified cohorts of 78 girls with epilepsy and 54 healthy control girls participated in this study (initial age 8 to 18.5 years, at follow-up 12.5 to 25.8 years). Thirty-five of the patients were initially taking valproate (VPA), 17 carbamazepine, and 17 oxcarbazepine as monotherapy. Most of the patients (61%) were off medication. All the subjects were examined clinically, the medical and menstrual histories were obtained, ovarian ultrasonography was examined, and serum reproductive hormone concentrations were analyzed. RESULTS: There were no significant differences in laboratory or clinical findings between the patients off medication and the control subjects. Postpubertal patients on medication had higher serum testosterone (1.9 nmol/L, SD 0.7 nmol/L) and androstenedione (18.8 nmol/L, SD 15.2 nmol/L) levels than patients off medication (1.4 nmol/L, SD 0.5 nmol/L, and 9.5 nmol/L, SD 2.6 nmol/L) or control subjects (1.4 nmol/L, SD 0.5 nmol/L, and 10.2 nmol/L, SD 3.2 nmol/L) (all comparisons p < 0.02). All patients still on VPA had elevated serum androstenedione levels. Polycystic ovary syndrome was more common in patients on medication (38%; in 63% on VPA, in 25% on other medication) than in patients off medication (6%) or in controls (11%) (p = 0.005). CONCLUSIONS: Epilepsy during pubertal maturation does not affect reproductive endocrine health in female subjects who discontinue the medication before adulthood. However, an increased prevalence of endocrine disorders is detected if the patients remain on antiepileptic drugs, especially VPA, until adulthood.

Effect of epilepsy and antiepileptic drugs on male reproductive health.

BACKGROUND: Men with epilepsy have reduced fertility, and antiepileptic drugs may affect semen quality. Moreover, animal studies suggest that valproate (VPA) may be associated with testicular atrophy. OBJECTIVE: To evaluate reproductive function in men with epilepsy. METHODS: Sixty men with epilepsy and 41 control men were evaluated for their reproductive health. Fifteen men were taking carbamazepine (CBZ) and 18 men oxcarbazepine (OXC) for partial epilepsy, and 27 men were taking VPA for generalized epilepsy. Reproductive hormones were assayed from serum samples, semen analysis and ultrasonography of the testicles were performed, and testicular volume was calculated. RESULTS: Men on CBZ had low serum dehydroepiandrosterone sulfate concentrations (p < 0.001), and men on VPA had high concentrations of serum androstenedione (p < 0.001). The frequency of morphologically abnormal sperm was higher among CBZ-treated (p < 0.01), OXC-treated (p < 0.05), and VPA-treated men (p < 0.01) than among the control men. Moreover, both CBZ and VPA were associated with poor motility of sperm (p < 0.05). In addition, the frequency of abnormally low sperm concentration was high in men on CBZ (p < 0.001), and the frequency of any sperm abnormality was high in men on VPA (p < 0.01). The VPA-treated men with abnormal sperm had smaller testicular volumes than the control men (p = 0.003). CONCLUSIONS: CBZ, OXC, and VPA are associated with sperm abnormalities in men with epilepsy. In addition, VPA-treated men with generalized epilepsy who have abnormal sperm may have reduced testicular volume.

Tooth by tooth survival analysis of dental health in girls with epilepsy.

AIM: The aim of this study was to analyse, tooth by tooth, the timing of caries attacks leading to dental restoration in girls with epilepsy. STUDY DESIGN: The series comprised 60 girls with epilepsy, 8-18 years old, treated in the Departments of Paediatrics or Neurology of the Oulu University Hospital. A group of healthy age matched girls served as control. METHODS: A tooth by tooth survival analysis of the time between tooth eruption and caries attacks to a stage leading to the restorations of the permanent teeth was conducted retrospectively using data from the dental health records with annual examinations. RESULTS: The rate of dental restorations placed due to caries was constantly higher in the girls with epilepsy than in their controls. STATISTICS: The difference was significant between the first molars (p=<0.03), second molars (p=<0.02) and central incisors (p=<0.02) in the maxilla. CONCLUSION: The present observation supports the hypothesis that factors related to epilepsy, the antiepileptic medication in particular, might increase the risk of caries.

Fasting serum insulin and lipid levels in men with epilepsy.

BACKGROUND: Previous studies suggest that obese women taking valproate (VPA) for epilepsy are insulin resistant. OBJECTIVE: To assess the effects of antiepileptic drugs on serum insulin and lipid levels in men with epilepsy. METHODS: Body mass index (BMI) and fasting serum concentrations of insulin and lipids were measured in 102 men with epilepsy who were treated with VPA, carbamazepine (CBZ), or oxcarbazepine (OXC) monotherapy. Thirty-two healthy men served as control subjects. RESULTS: Obesity was not more common among VPA-treated men than among other men with epilepsy or the control subjects. However, the obese VPA-treated men had higher serum insulin levels (p < 0.001) than the obese control subjects despite similar BMI. CBZ and OXC did not have any significant effect on any of the measurements. Fasting serum insulin concentrations above the normal range were observed in seven obese VPA-treated patients (35%) but in only one obese control subject (5%). Five obese VPA-treated patients (25%) and one obese control subject (5%) had serum triglyceride levels above the normal range, and a low high-density lipoprotein/total cholesterol ratio was observed in two obese VPA-treated patients (10%). CONCLUSIONS: Obese valproate-treated men have high serum insulin levels, indicating insulin resistance. Moreover, some of the valproate-treated men cluster cardiovascular risk factors such as obesity, hyperinsulinemia, and elevated serum triglyceride concentrations. CBZ and OXC do not seem to have any significant effects on serum insulin or lipid levels in men with epilepsy.

Reproductive dysfunction in women with epilepsy: recommendations for evaluation and management.

BACKGROUND: Epilepsy is commonly associated with reproductive endocrine disorders. These include polycystic ovary syndrome (PCOS), isolated components of this syndrome such as polycystic ovaries, hyperandrogenaemia, hypothalamic amenorrhoea, and functional hyperprolactinaemia. OBJECTIVE: To summarise the currently known relations between epilepsy and reproductive endocrine disorders. METHODS: A review of clinical experience and published reports. RESULTS: The most likely explanations for endocrine disorders related to epilepsy or antiepileptic drugs are: (1) a direct influence of the epileptogenic lesion, epilepsy, or antiepileptic drugs on the endocrine control centres in the brain; (2) the effects of antiepileptic drugs on peripheral endocrine glands; (3) the effects of antiepileptic drugs on the metabolism of hormones and binding proteins; and (4) secondary endocrine complications of antiepileptic drug related weight changes or changes of insulin sensitivity. Regular monitoring of reproductive function at visits is recommended, including questioning about menstrual disorders, fertility, weight, hirsutism, and galactorrhoea. Particular attention should be paid to patients on valproate and obese patients or those experiencing significant weight gain. Single abnormal laboratory or imaging findings without symptoms may not constitute a clinically relevant endocrine disorder. However, patients with these kinds of abnormalities should be monitored to detect the possible development of a symptomatic disorder associated with, for example, menstrual disorders or fertility problems. CONCLUSIONS: If a reproductive endocrine disorder is found, antiepileptic drug treatment should be reviewed to ensure that it is correct for the particular seizure type and that it is not contributing to the endocrine problem. The possible benefits of a change in treatment must be balanced against seizure control and the cumulative side effect of alternative agents.

Heart rate dynamics in refractory and well controlled temporal lobe epilepsy.

OBJECTIVES: Disorders of cardiovascular and other autonomic nervous system functions are often found in patients with temporal lobe epilepsy (TLE). Cardiovascular dysregulation in TLE has previously been quantified assessing traditional time and frequency domain measures of heart rate (HR) variability from short term ECG recordings. However, new complexity and fractal measures of HR variability based on non-linear dynamics and fractals ("chaos theory") may disclose certain patterns of HR dynamics that cannot be detected using only conventional measures. METHODS: In addition to the traditional spectral and non-spectral components of HR variability, fractal correlation properties, approximate entropy (ApEn) of RR interval dynamics, and the slope of the power law relation were measured from 24 hour ambulatory ECG recordings to evaluate interictal autonomic cardiovascular regulatory function in 19 patients with refractory TLE, 25 patients with well controlled TLE, and in 34 healthy age and sex matched control subjects. RESULTS: The traditional time and frequency domain measures were lower in patients with TLE than in controls (p<0.05). In addition, the power law slope (p<0.005) and ApEn (p<0.05) were also reduced in TLE patients. Furthermore, ApEn was smaller in patients with refractory TLE than in patients with well-controlled TLE ( p<0.01), whereas the long term fractal correlation value alpha2 was lower in patients with well controlled TLE (p<0.05). An altered HR variation was not associated with any particular AED regimen. CONCLUSIONS: In addition to reduced overall HR variability, the long term fractal organisation and complexity of HR dynamics seem to be altered in TLE. These abnormalities in HR behaviour may partly contribute to the occurrence of adverse cardiovascular events, such as life threatening arrhythmias in patients with TLE.

Altered ovarian function and cardiovascular risk factors in valproate-treated women.

PURPOSE: Polycystic ovaries and menstrual disturbances seem to be common among women taking valproate for epilepsy. The purpose of the present study was to assess the frequency of valproate-related metabolic and endocrine disorders in different groups of women with epilepsy. SUBJECTS AND METHODS: Seventy-two women with epilepsy and 52 control subjects from centers in three European countries (Finland, Norway, and the Netherlands) participated in the study. Thirty-seven of the women with epilepsy were taking valproate monotherapy and 35 carbamazepine monotherapy. RESULTS: The frequency of polycystic ovaries or hyperandrogenism, or both, among valproate-treated women with epilepsy was 70% (26 of 37) compared with 19% (10 of 52) among control subjects (P <0.001). They were found in 79% (11 of 14) of obese and 65% (15 of 23) of lean women on valproate, and in 20% (7 of 35) of carbamazepine-treated women. The obese valproate-treated women with polycystic ovaries or hyperandrogenism, or both, had hyperinsulinemia and associated unfavorable changes in serum lipid levels consistent with insulin resistance. CONCLUSIONS: Polycystic ovaries and related hyperandrogenism are frequently encountered in both obese and lean women taking valproate for epilepsy. The use of valproate is associated with risk factors for cardiovascular disease in obese women.

Early hormonal changes during valproate or carbamazepine treatment: a 3-month study.

BACKGROUND: Long-term treatment with valproate (VPA) or carbamazepine (CBZ) may induce reproductive endocrine disorders in patients with epilepsy. METHODS: Serum concentrations of reproductive hormones were studied in 17 women and 22 men with recently diagnosed epilepsy before they started either VPA or CBZ medication, and 1 and 3 months later. RESULTS: No weight gain or clinical signs of hormonal disorders were observed during the follow-up. The mean serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin (SHBG) increased, and dehydroepiandrosterone sulfate (DHEAS) decreased, in women starting VPA. Serum testosterone levels increased in half of the women on VPA. Serum concentrations of progesterone and dehydroepiandrosterone increased, and gonadotropins decreased, in men on VPA during the follow-up. Serum SHBG levels increased and DHEAS decreased during the first months of CBZ treatment in both sexes. In addition, the free-androgen index decreased in men after starting CBZ. CONCLUSIONS: Hormonal changes occur after only 1 month's use of VPA or CBZ. VPA-treatment seems to be associated with increased serum androgen levels, but the profile of hormonal changes appears to be different in women than in men. The use of CBZ, in turn, was associated with increased SHBG concentrations and thus with diminished sex steroid function in both sexes. The women with increased serum testosterone levels in the early phase of VPA medication may be at increased risk for VPA-related endocrine disorders later during treatment.

Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy.

PURPOSE: Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This study aimed to evaluate thyroid function in men taking carbamazepine (CBZ), oxcarbazepine (OCBZ), or valproate (VPA) for epilepsy. METHODS: Ninety men with epilepsy (40 taking CBZ, 29 taking OCBZ, and 21 taking VPA monotherapy) and 25 control subjects participated in the study. After clinical examination, a blood sample for hormone, gamma-glutamyl-transferase (GGT) and antibody (ab) assays was obtained. RESULTS: Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in men taking CBZ or OCBZ. Forty-five percent of men taking CBZ and 24% of men taking OCBZ had serum T4 and/or FT4 levels below the reference range. However, no correlations were found between T4 or FT4 and GGT concentrations in men taking CBZ or OCBZ. Thirteen percent of men taking CBZ, 17% of men taking OCBZ, and 6% of control men had increased levels of thyroid peroxidase (TPO)-ab and/or thyroglobulin (TG)-ab, but these were not associated with altered serum thyroid hormone concentrations. Serum triiodothyronine and thyrotropin levels in men taking CBZ or OCBZ were normal. In men taking VPA, the concentrations of thyroid hormones, thyrotropin, and antithyroid ab were normal. CONCLUSIONS: Serum thyroid hormone concentrations are low in CBZ- or OCBZ-treated men. However, these low levels do not seem to be due to liver enzyme induction or activation of immunologic mechanisms. Therefore, interference with hypothalamic regulation of thyroid function by CBZ and OCBZ seems possible. VPA does not have any significant effects on thyroid function.

The regulation of serum sodium after replacing carbamazepine with oxcarbazepine.

PURPOSE: To evaluate changes in serum electrolyte balance and underlying regulatory mechanisms in 10 male patients with epilepsy 2 and 6 months after replacing long-term carbamazepine (CBZ) monotherapy with oxcarbazepine (OCBZ) monotherapy. Arginine vasopressin (AVP) is thought to be most important underlying mechanism of CBZ-related hyponatremia via direct or kidney tubular mechanisms. Furthermore, AVP is as well hormonally regulated by the renin-angiotensin-aldosterone system and atrial natriuretic peptide (ANP). METHODS: The medication of the patients was changed from CBZ to OCBZ. Serum electrolytes, creatinine, albumin, aldosterone, and the N-terminal fragment of ANP (NT-proANP) concentrations were measured before and 2 and 6 months after the change in the medication. RESULTS: The mean serum sodium level diminished after the medication was changed. Serum sodium levels decreased below the reference range in two (20%) patients during OCBZ medication. Serum sodium levels decreased altogether in four patients, and remained unaltered in six patients. Serum aldosterone levels increased in the six patients whose serum sodium concentrations did not decrease, but no increase was found in the patients with decreased sodium levels during OCBZ medication. Serum NT-proANP levels decreased in all patients. CONCLUSIONS: Serum sodium levels decrease after replacing CBZ with OCBZ. The low serum NT-proANP concentrations appear to reflect the decreased serum sodium levels, but a compensatory aldosterone response may prevent the development of hyponatremia in some patients during OCBZ medication.