Markus Rauchenzauner

Non-alcoholic fatty liver disease (NAFLD), insulin resistance and lipid profile in antiepileptic drug treatment.

PURPOSE Patients undergoing long-term treatment with valproic acid (VPA) are prone to develop different features of the metabolic syndrome (MS). The aim of the present study was to evaluate the occurrence of non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR) and a pro-atherogenic lipid profile in patients undergoing VPA, carbamazepine (CBZ) and lamotrigine (LTG) monotherapy compared to healthy controls. METHODS Abdominal ultrasound as well as measurement of serum fasting insulin and glucose, serum lipids and liver function parameters were performed in VPA (n=23), CBZ (n=22) and LTG (n=23) treated non-diabetic and non-obese epileptic patients compared to healthy controls (n=16). RESULTS Ultrasound measurement demonstrated characteristics of fatty liver disease in 60.9% of VPA, in 22.7% of CBZ, in 8.7% of LTG treated patients and in 12.5% of the healthy controls, with highest level of steatosis seen in VPA treated patients. In addition, patients on VPA monotherapy showed a higher body-mass index (BMI) when compared to LTG treated patients and controls (p<or=0.049). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and gamma-glutamyltransferase (gammaGT) were greatest in the CBZ group (p<or=0.043). Interestingly, serum fasting glucose, serum fasting insulin as well as the HOMA-IR did not differ significantly between groups. CONCLUSION In conclusion, VPA (and moderately CBZ) therapy is related to increased risk for ultrasonographic signs of fatty liver disease, emphasizing the importance of regular ultrasound measurements as well as monitoring of serum lipids and BMI during enzyme-modulating AED treatment.

Valproate, weight gain and carbohydrate craving: A gender study

PURPOSE To compare the incidence and magnitude of weight gain associated with valproic acid (VPA) monotherapy in male and female epilepsy patients and to determine possible gender-specific differences in frequency of carbohydrate craving, body-composition, glucose homeostasis and lipid metabolism. METHODS Epilepsy patients on VPA monotherapy were consecutively recruited at the outpatient clinic of the Department of Neurology, Innsbruck Medical University. Weight gain during VPA-therapy, frequency of carbohydrate craving and physical exercise, sociopsychological problems and family history for diabetes were obtained from all patients. Clinical data also comprised body-impedance analysis, body mass index and waist-to-hip ratio. Morning fasting blood samples were drawn to determine serum leptin, glucose and lipid concentrations, as well as insulin, C-reactive protein and TNF-alpha. RESULTS One hundred and six patients (55 women) were enrolled in the study. Significant weight gain was seen during VPA-therapy in both genders (each p<0.001) with women experiencing increment of weight more frequently and more pronounced than did men. Analyses of patients who gained weight during VPA-therapy revealed significantly higher serum leptin concentrations in women than in men (p<0.001). Women also revealed significantly higher high-density lipoprotein-cholesterol and lower triglyceride concentrations than men (p=0.004 and 0.014, respectively). Frequency of carbohydrate craving was 25.8% in women and 14.3% in men. More women tried to lose or control weight through diet than did men (22.6% versus 7.1%). Moreover, weight gain as a sociopsychological problem was more numorous in women than in men. CONCLUSION Women are more prone to gain weight during VPA therapy though higher frequency of diet and sociopsychological burden than men, which might possibly be related to leptin-resitance and a higher frequency of carbohydrate craving.

Epilepsy and hormones: a critical review.

Especially during growth, puberty, and menopause, profound changes including maturation of the growth hormone, sex steroid, and thyroid axes, as well as alterations in lipid homeostasis, cardiac integrity, and other enzyme systems, occur physiologically. With epilepsy, however, things are often changing, and there may be a complicated interplay between hormones, epilepsy, and antiepileptic drugs (AEDs). On the one hand, epilepsy itself possibly elicits diverse effects on different enzyme systems including sex steroids, the neuro-cardio-endocrine axis, and bone health. On the other hand, different AEDs are known to induce neuroendocrine changes (e.g., lipid metabolism) that may have deleterious consequences on health and well-being later in life. It is important for physicians and epileptologists to have in mind and to consider the endocrine effects induced by epilepsy itself or by a certain AED when starting antiepileptic therapy, especially when it is expected that long-term treatment will be necessary.

Differential effects of levetiracetam, carbamazepine, and lamotrigine on reproductive endocrine function in adults.

Animal studies have shown endocrine changes after levetiracetam treatment. The present study investigated reproductive and sexual function in patients with epilepsy (aged 18-45) treated with levetiracetam (LEV: 30 men/26 women), carbamazepine (CBZ: 63 men/30 women), or lamotrigine (LTG: 37 men/40 women) monotherapy and in healthy controls (36 men/44 women). In women, no endocrine changes were observed during LEV treatment, whereas steroid hormone-binding globulin levels were greater and progesterone levels lower in women using CBZ. Dehydroepiandrosterone sulfate levels were higher and androstenedione levels lower in LTG-treated women. Arizona Sexual Experience Scale scores, which were significantly lower in females using LTG or LEV, suggesting they have better sexual function than CBZ users and controls. In men, no drug-specific hormonal pattern was observed after LEV treatment. Male patients in all treatment groups had lower androstenedione and free testosterone. Those using CBZ had lower free androgen indices and dehydroepiandrosterone sulfate levels, and higher steroid hormone-binding globulin, follicle-stimulating hormone, and luteinizing hormone levels. Arizona Sexual Experience Scale scores for men were similar in all groups. In conclusion, LEV treatment apparently has no drug-specific sexual or endocrine side effects in men or women in this age group.

Effect of valproic acid treatment on body composition, leptin and the soluble leptin receptor in epileptic children

PURPOSE The aim of the study was to determine the influence of valproic acid (VPA) treatment on leptin, the soluble leptin receptor (sOB-R), the sOB-R/leptin ratio, body composition and insulin resistance in epileptic children. METHODS A cross-sectional cohort study was conducted at the Medical University Innsbruck, Austria. Children >6 years with idiopathic epilepsy and antiepileptic drug therapy since at least six months were eligible. Leptin concentration, the sOB-R, the sOB-R/leptin ratio, body composition and glucose homeostasis were determined. RESULTS 87 children (median [range] age 12.8 years [6.0-18.6]) were on treatment with VPA, 55 (12.3 years [6.4-18.3]) on other AEDs, comprising the non-VPA group. VPA-treated children had higher leptin concentrations, body-mass-index standard-deviation score (SDS), body fat (each p<0.001), serum insulin concentrations (p=0.014) and homeostasis model assessment (HOMA) index (p=0.009), as well as a lower sOB-R/leptin ratio (p<0.001) when compared to the non-VPA group. Overweight VPA-treated children showed lower sOB-R concentrations and a lower sOB-R/leptin ratio (each p<0.001) as well as higher body fat and leptin levels (each p<0.001) compared to lean VPA-treated children. CONCLUSION VPA monotherapy was associated with higher body weight, body fat and serum leptin concentrations as well as impaired glucose homeostasis. Low sOB-R concentrations and a low sOB-R/leptin ratio in overweight VPA-treated patients might contribute to disturbances in glucose homeostasis and to the development of the metabolic syndrome in these children later in life.

Amino Acid Cerebrospinal Fluid/Plasma Ratios in Children: Influence of Age, Gender, and Antiepileptic Medication

OBJECTIVE. The purpose of this work was to investigate the influence of age, gender, and antiepileptic therapy on amino acid cerebrospinal fluid/plasma ratios in children. PATIENTS AND METHODS. Concentrations of 17 amino acids measured by ion-exchange chromatography with ninhydrin detection in plasma and cerebrospinal fluid from 68 patients with neurologic diseases were used to calculate their cerebrospinal fluid/plasma ratios (70 measurements; 28 female patients [29 punctures] and 40 male patients [41 punctures]). Age dependence and the effects of gender and antiepileptic medication on amino acid cerebrospinal fluid/plasma ratios were investigated by linear multiple regression analysis, and nonstandardized predicted mean values for 2 age groups were calculated (cutoff: 3 years old). RESULTS. The cerebrospinal fluid/plasma ratios ranged between 0.02 for glycine and 0.93 for glutamine. Age had a significant influence on cerebrospinal fluid/plasma ratios for valine, isoleucine, leucine, and tyrosine, with higher ratios in younger children. Gender had a significant influence only on the glutamine cerebrospinal fluid/plasma ratio (female patients had lower ratios). Cerebrospinal fluid/plasma ratios of glutamine and tyrosine were significantly elevated by valproate therapy and those of serine, asparagine, glutamine, valine, methionine, and phenylalanine by phenobarbital therapy. No significant influence of age, gender, and antiepileptic drugs was detectable on cerebrospinal fluid/plasma ratios of threonine, proline, glycine, alanine, histidine, ornithine, lysine, and arginine. CONCLUSIONS. Cerebrospinal fluid/plasma ratios, especially for essential neutral amino acids and for serine, asparagine, and glutamine were influenced to different degrees by age, gender, and antiepileptic therapy.

Chronic antiepileptic monotherapy, bone metabolism, and body composition in non-institutionalized children.

Aim  The aim of this study was to determine the influence of chronic monotherapy with antiepileptic drugs (AEDs) on vitamin D levels, bone metabolism, and body composition.

Six-Minute Walk Distance in Overweight Children and Adolescents: Effects of a Weight-Reducing Program

OBJECTIVE To assess the significance of consecutive six-minute walk tests (6MWTs) during a weight reduction program. STUDY DESIGN Overweight children and adolescents (n = 113; mean ± standard deviation age, 12.9 ± 2.0 years; 64 girls) performed a standardized 6MWT at the beginning and end of an in-patient weight reduction program consisting of exercise, diet, and educational and psychological support. Their 6-minute walk distance (6MWD) was compared with age- and sex-matched normal-weight children (n = 353). RESULTS Preintervention 6MWD averaged 93% of control subjects (631 ± 88 m versus 675 ± 70 m, P < .001) and increased significantly to 667 ± 90 m (P < .001) after 27 ± 7 days of intervention (99% of control subjects; P = .260). Participants reduced their body weight from 80.9 ± 19.8 kg to 75.6 ± 19.0 kg, body mass index (BMI) percentile from 98.2 ± 2.1% to 96.8 ± 3.8%, and BMI-standard deviation score from 2.37 ± 0.6 to 2.13 ± 0.6 (P < .001 for each variable). BMI-standard deviation score, height, and the change in heart rate during the 6MWT were significant independent predictors of the 6MWD at preintervention and at post intervention time points (P < .001 each). CONCLUSIONS The 6MWD increases during a weight reduction program, indicating improvement of physical fitness and decreased metabolic demand during daily activities in overweight children. The 6MWT represents a practical and reliable assessment tool for exercise performance in overweight children and adolescents.

Brain-type Natriuretic Peptide Secretion Following Febrile and Afebrile Seizures—A New Marker in Childhood Epilepsy?

Summary:  Purpose: Markers for epileptic seizures are rare and their use has not been established in the evaluation of seizures and febrile convulsions (FC). Brain‐type natriuretic peptide (BNP) is a natriuretic, diuretic, and vasodilator compound first discovered in the hypothalamus but mainly synthesized in the myocardium. The aim of this study was to assess whether epileptic seizures or FC are related to increased secretion of the N‐terminal fragment of BNP (NT‐proBNP).

Cardiovascular risk factors in epilepsy patients taking levetiracetam, carbamazepine or lamotrigine

Svalheim S, Luef G, Rauchenzauner M, Mørkrid L, Gjerstad L, Taubøll E. Cardiovascular risk factors in epilepsy patients taking levetiracetam, carbamazepine or lamotrigine. Acta Neurol Scand: 2010: 122 (Suppl. 190): 30–33.