Erik Taubøll

Oslo University Hospital, Kristiania (historical), Oslo, Norway

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Publications (123)263.97 Total impact

  • E. Taubøll · K. Heuser · L. Sveberg · S. Svalheim
    Zeitschrift für Epileptologie 06/2015; DOI:10.1007/s10309-015-0001-x
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    ABSTRACT: Astrocytic endfeet are specialized cell compartments whose important homeostatic roles depend on their enrichment of water and ion channels anchored by the dystrophin associated protein complex (DAPC). This protein complex is known to disassemble in patients with mesial temporal lobe epilepsy and in the latent phase of experimental epilepsies. The mechanistic underpinning of this disassembly is an obvious target of future therapies, but remains unresolved. Here we show in a kainate model of temporal lobe epilepsy that astrocytic endfeet display an enhanced stimulation-evoked Ca(2+) signal that outlast the Ca(2+) signal in the cell bodies. While the amplitude of this Ca(2+) signal is reduced following group I/II metabotropic receptor (mGluR) blockade, the duration is sustained. Based on previous studies it has been hypothesized that the molecular disassembly in astrocytic endfeet is caused by dystrophin cleavage mediated by Ca(2+) dependent proteases. Using a newly developed genetically encoded Ca(2+) sensor, the present study bolsters this hypothesis by demonstrating long-lasting, enhanced stimulation-evoked Ca(2+) signals in astrocytic endfeet.
    Frontiers in Cellular Neuroscience 02/2015; 9:49. DOI:10.3389/fncel.2015.00049 · 4.29 Impact Factor
  • Sigrid Svalheim · Line Sveberg · Monika Mochol · Erik Taubøll
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    ABSTRACT: Antiepileptic drugs (AEDs) are known to have endocrine side effects in both men and women. These can affect fertility, sexuality, thyroid function, and bone health, all functions of major importance for well-being and quality of life. The liver enzyme inducing antiepileptic drugs (EIAEDs), like phenobarbital, phenytoin, and carbamazepine, and also valproate (VPA), a non-EIAED, are most likely to cause such side effects. AED treatment can alter the levels of different sex hormones. EIAEDs increase sex hormone binding globulin (SHBG) concentrations in both men and women. Over time, this elevation can lead to lower levels of bioactive testosterone and estradiol, which may cause menstrual disturbances, sexual problems, and eventually reduced fertility. VPA can cause weight gain in both men and women. In women, VPA can also lead to androgenization with increased serum testosterone concentrations, menstrual disturbances, and polycystic ovaries. Lamotrigine has not been shown to result in endocrine side effects. The newer AEDs have not yet been thoroughly studied, but case reports indicate that some of these drugs could also be suspected to cause such effects if endocrine changes commence after treatment initiation. It is important to be aware of possible endocrine side effects of AEDs as they can have a major impact on quality of life, and are, at least partly, reversible after AED discontinuation. Copyright © 2015. Published by Elsevier Ltd.
    Seizure 02/2015; 28. DOI:10.1016/j.seizure.2015.02.022 · 1.82 Impact Factor
  • Erik Taubøll · Line Sveberg · Sigrid Svalheim
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    ABSTRACT: There is a complex, bidirectional interdependence between sex steroid hormones and epilepsy; hormones affect seizures, while seizures affect hormones thereby disturbing reproductive endocrine function. Both female and male sex steroid hormones influence brain excitability. For the female sex steroid hormones, progesterone and its metabolites are anticonvulsant, while estrogens are mainly proconvulsant. The monthly fluctuations in hormone levels of estrogen and progesterone are the basis for catamenial epilepsy described elsewhere in this issue. Androgens are mainly anticonvulsant, but the effects are more varied, probably because of its metabolism to, among others, estradiol. The mechanisms for the effects of sex steroid hormones on brain excitability are related to both classical, intracellularly mediated effects, and non-classical membrane effects due to binding to membrane receptors. The latter are considered the most important in relation to epilepsy. The different sex steroids can also be further metabolized within the brain to different neurosteroids, which are even more potent with regard to their effect on excitability. Estrogens potentiate glutamate responses, primarily by potentiating NMDA receptor activity, but also by affecting GABA-ergic mechanisms and altering brain morphology by increasing dendritic spine density. Progesterone and its main metabolite 5α-pregnan-3α-ol-20-one (3α-5α-THP) act mainly to enhance postsynaptic GABA-ergic activity, while androgens enhance GABA-activated currents. Seizures and epileptic discharges also affect sex steroid hormones. There are close anatomical connections between the temporolimbic system and the hypothalamus controlling the endocrine system. Several studies have shown that epileptic activity, especially mediated through the amygdala, alters reproductive function, including reduced ovarian cyclicity in females and altered sex steroid hormone levels in both genders. Furthermore, there is an asymmetric activation of the hypothalamus with unilateral amygdala seizures. This may, again, be the basis for the occurrence of different reproductive endocrine disorders described for patients with left-sided or right-sided temporal lobe epilepsy. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
    Seizure 02/2015; 28. DOI:10.1016/j.seizure.2015.02.012 · 1.82 Impact Factor
  • Line Sveberg · Sigrid Svalheim · Erik Taubøll
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    ABSTRACT: The treatment of women with epilepsy during pregnancy is known to increase the risk of teratogenic effects. Whether seizures during pregnancy have a deleterious effect on the developing child is difficult to determine, but recent animal studies, case studies, cohort studies and population studies have provided useful insights. Seizures before pregnancy are a predictor for seizures during pregnancy, and catamenial epilepsy may also predict the course of seizures during pregnancy. A first epileptic seizure may also have implications for the pregnancy, depending on the seizure aetiology. Seizures affecting maternal awareness and responsiveness may have cardiac effects on the foetus and may impact on the weight of the newborn. Status epilepticus in pregnancy is rare, but isolated cases of perinatal death and malformations after status epilepticus have been reported in women on antiepileptic drugs. Seizures during delivery occur in about 2% of pregnancies of women with epilepsy, and case studies indicate that the foetal heart may be affected. However, a diagnosis of epilepsy is not an indication per se for caesarean delivery. A well-planned pregnancy can reduce the likelihood of seizures occurring. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
    Seizure 02/2015; 28. DOI:10.1016/j.seizure.2015.02.020 · 1.82 Impact Factor
  • Line Sveberg · Kristin Vik · Tore Henriksen · Erik Taubøll
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    ABSTRACT: Guidelines for women with epilepsy (WWE) are advising those on enzyme inducing drugs EIAEDs to take vitamin K the last month of pregnancy. The primary aim of this study was to investigate whether WWE have a higher frequency of large post partum hemorrhage. Secondary we wanted to see if this was more severe in women taking EIAEDs, and also to evaluate whether those receiving prenatal vitamin K supplementation have a less pronounced risk. All patients (n=109), with the diagnosis of epilepsy giving birth at OUS Rikshospitalet from 2006 to 2011 were selected to be in the epilepsy group. They were compared to controls with regard to the amount of post partum hemorrhage, gestational age for the mother, birth weight and APGAR score in the newborns. No significant difference between the groups regarding post partum hemorrhage, gestational age, birthweight or APGAR score in the newborn was found. Also, comparing the WWE using EIAED who received prenatal vitamin K with those who did not receive vitamin K, no significant difference in post partum hemorrhage could be demonstrated. In this study, WWE was not found to have increased risk of post partum hemmorrhage including those using EIAED with/without vitamin K supplementation. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
    Seizure 02/2015; 28. DOI:10.1016/j.seizure.2015.02.021 · 1.82 Impact Factor
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    ABSTRACT: Fructose reacts spontaneously with proteins in the brain to form advanced glycation end products (AGE) that may elicit neuroinflammation and cause brain pathology, including Alzheimer's disease. We investigated whether fructose is eliminated by oxidative metabolism in neocortex. Injection of [(14) C]fructose or its AGE-prone metabolite [(14) C]glyceraldehyde into rat neocortex in vivo led to formation of (14) C-labeled alanine, glutamate, aspartate, GABA, and glutamine. In isolated neocortical nerve terminals, [(14) C]fructose labeled glutamate, GABA, and aspartate, indicating uptake of fructose into nerve terminals and oxidative fructose metabolism in these structures. This was supported by high expression of Hexokinase 1, which channels fructose into glycolysis, and whose activity was similar to fructose or glucose as substrates. By contrast, the fructose-specific ketohexokinase was weakly expressed. The fructose transporter Glut5 was expressed at only 4% of the level of neuronal glucose transporter Glut3, suggesting transport across plasma membranes of brain cells as the limiting factor in removal of extracellular fructose. The genes encoding aldose reductase and sorbitol dehydrogenase, enzymes of the polyol pathway that forms glucose from fructose, were expressed in rat neocortex. These results point to fructose being transported into neocortical cells, including nerve terminals, and that it is metabolized and thereby detoxified primarily through hexokinase activity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 02/2015; 133(4). DOI:10.1111/jnc.13079 · 4.28 Impact Factor
  • Gerhard Luef · Erik Taubøll
    Seizure 02/2015; 28. DOI:10.1016/j.seizure.2015.02.001 · 1.82 Impact Factor
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    ABSTRACT: 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 studyTo 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.ResultsAfter 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.
    Acta Neurologica Scandinavica 10/2014; 131(3). DOI:10.1111/ane.12330 · 2.40 Impact Factor
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    ABSTRACT: Background: In pregnant women with epilepsy the use of antiepileptic drugs may increase the risk of harming the foetus. For the treating neurologist it may be challenging to find a balance between optimal seizure control and the lowest possible drug dosage. The aim of this study was to assess the prevalence and type of congenital malformations in children exposed to antiepileptic drugs during pregnancy. Material and method: In Norway we have prospectively followed 813 pregnancies in women with epilepsy as part of an international cohort study. The women had three check-ups during the pregnancy, and the children were followed up twice during their first year of life. Results: We found a total of 34 congenital malformations in the children, of which 12 were heart defects, yielding a malformation rate of 4.5%. Six of the malformations (18%) were detected prenatally, 20 (59%) were reported immediately after birth, and eight (24%) were discovered during the child's first year of life. Interpretation: Our study shows that 95.5%.of the women included who used antiepileptic drugs during pregnancy gave birth to a healthy child. This Norwegian cohort is too small to evaluate the teratogenic risk associated with the individual drugs.
    Tidsskrift for den Norske laegeforening 07/2014; 134(12-13):1239-42. DOI:10.4045/tidsskr.13.1349
  • Seizure 04/2014; 23(4). DOI:10.1016/j.seizure.2014.01.010 · 1.82 Impact Factor
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    ABSTRACT: Objective: Febrile seizures (FS) are the most common seizure type in young children. Complex FS are a risk factor for mesial temporal lobe epilepsy (mTLE). To identify new FS susceptibility genes we used a forward genetic strategy in mice and subsequently analyzed candidate genes in humans. Methods: We mapped a quantitative trait locus (QTL1) for hyperthermia-induced FS on mouse chromosome 1, containing the signal recognition particle 9 (Srp9) gene. Effects of differential Srp9 expression were assessed in vivo and in vitro. Hippocampal SRP9 expression and genetic association were analyzed in FS and mTLE patients. Results: Srp9 was differentially expressed between parental strains C57BL/6J and A/J. Chromosome substitution strain 1 (CSS1) mice exhibited lower FS susceptibility and Srp9 expression than C57BL/6J mice. In vivo knockdown of brain Srp9 reduced FS susceptibility. Mice with reduced Srp9 expression and FS susceptibility, exhibited reduced hippocampal AMPA and NMDA currents. Downregulation of neuronal Srp9 reduced surface expression of AMPA receptor subunit GluA1. mTLE patients with antecedent FS had higher SRP9 expression than patients without. SRP9 promoter SNP rs12403575(G/A) was genetically associated with FS and mTLE. Interpretation: Our findings identify SRP9 as a novel FS susceptibility gene and indicate that SRP9 conveys its effects through endoplasmic reticulum (ER)-dependent synthesis and trafficking of membrane proteins, such as glutamate receptors. Discovery of this new FS gene and mechanism may provide new leads for early diagnosis and treatment of children with complex FS at risk for mTLE.
    03/2014; 1(4):239-250. DOI:10.1002/acn3.48
  • Kjell Heuser · Karolina Szokol · Erik Taubøll
    Tidsskrift for den Norske laegeforening 02/2014; 134(3):273. DOI:10.4045/tidsskr.14.0050
  • Karl O Nakken · Erik Taubøll
    Tidsskrift for den Norske laegeforening 01/2014; 134(2):144-5. DOI:10.4045/tidsskr.13.1350
  • Kjell Heuser · Karolina Szokol · Erik Taubøll
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    ABSTRACT: BACKGROUND Brain research in the last century was mainly directed at neurons, with the role of glia assumed to be limited to repair, supplying nutrients and above all acting as a packing material between neurons. In recent years, the importance of glial cells for normal brain function has been recognised. This article summarizes knowledge of glial cells of relevance to epilepsy.METHOD The article is based on a literature search in PubMed as well as the authors' clinical and research experience.RESULTS Astrocytes are the largest subgroup of glial cells and, in common with neurons, have diverse membrane transporters, ion channels and receptors. Among the most important roles of astrocytes are the uptake and redistribution of ions and water, glucose metabolism and communication with nerve cells. Disturbances in all of these functions have been associated with epilepsy.INTERPRETATION Epilepsy has previously been regarded as exclusively a disturbance in the functioning of neurons and especially of their contact points, the synapses. The mechanisms of action of today's anti-epileptic drugs are therefore primarily directed at neuronal channels and receptors. New knowledge of the role played by glial cells could increase our understanding of how epilepsy arises and could lead to new treatment strategies.
    Tidsskrift for den Norske laegeforening 01/2014; 134(1):37-41. DOI:10.4045/tidsskr.12.1344
  • Karl O Nakken · Kjell Heuser · Kristin Alfstad · Erik Taubøll
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    ABSTRACT: Background: There are currently around 25 antiepileptic drugs in use in Norway, of which 15 have entered the market in the last 20 years. All have somewhat different effect- and adverse effect profiles and mechanisms of action. Here we present a brief overview of current knowledge regarding the basic mechanisms of action of these drugs. Method: The review is based on a discretionary selection of relevant articles found through a literature search in PubMed and our own clinical and research experience. Results: There are, roughly speaking, four main mechanisms; 1) modulation of ion channels (sodium and calcium channel blockers, potassium channel openers), 2) potentiation of GABAergic inhibition, 3) reduction of glutamatergic excitation and 4) modulation of presynaptic neurotransmitter release. Some of the drugs have several mechanisms of action, and for some of them it is unclear which mechanism is clinically most important. To some extent, the drugs' mechanisms of action predict their effect against different types of epilepsy and seizures. For instance, sodium channel blockers work best against focal seizures, while calcium channel blockers work best against absences, a type of generalised seizure. Interpretation: Optimal treatment of patients with epilepsy requires not only thorough knowledge of seizure- and epilepsy classification, but also insight into the mechanisms of action of antiepileptic drugs.
    Tidsskrift for den Norske laegeforening 01/2014; 134(1):42-6. DOI:10.4045/tidsskr.13.0761
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    ABSTRACT: Histone deacetylases (HDACs) are often overexpressed in cancer cells, leading to altered expression and activity of numerous proteins involved in carcinogenesis. Recent evidence suggests that expression of class I HDACs is increased in ovarian carcinomas and plays a significant role in carcinogenesis and resistance to chemotherapeutic agents. Two compounds, valproic acid (VPA) and levetiracetam (LEV), exhibit HDAC inhibitor (HDACI) activity in various cell types, but data concerning their activity in ovarian cancer are lacking. Here we compared the effects of VPA and LEV as HDACIs, using a human ovarian cancer cell line, OVCAR-3. Cells were cultured with VPA or LEV at concentrations between 1 and 10mM for 1 to 24h. HDAC activity was determined by fluorometric assay and confirmed by western blotting. Expression of HDAC genes was determined by real-time PCR and HDAC proteins expression was evaluated by western blotting. Additionally, we used high-performance liquid chromatography to determine whether OVCAR-3 cells can metabolize LEV to its major metabolite, 2-pyrrolidinone-n-butyric acid (PBA), which might exert HDACI activity. LEV, however, had no apparent effect on HDAC activity, or gene and protein expression. The OVCAR-3 cell line was able to metabolize LEV to PBA, but the effect was small. Our observations suggest that VPA should be considered as a possible adjunctive drug in ovarian cancer treatment.
    Toxicology Letters 11/2013; 224(2). DOI:10.1016/j.toxlet.2013.10.035 · 3.26 Impact Factor
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    ABSTRACT: The long QT syndrome (LQTS) is an inherited cardiac channelopathy associated with syncope and sudden cardiac death due to ventricular arrhythmias and most frequently caused by potassium channel mutations. Potassium channels are also expressed in brain tissue and play an important role in idiopathic epilepsies. Recent reports have indicated that LQTS-related potassium channel mutations may co-express as concomitant epilepsy and LQTS. To explore cerebral activity by means of EEG recordings in individuals with LQTS related to potassium channel mutations. Seventeen individuals with confirmed LQTS related to potassium channel mutations (11 LQT1 and 6 LQT2) were prospectively studied with 21-channel electroencephalography (EEG). LQTS-related symptoms, co-morbidity, medication and QTc (12-lead ECG) were recorded. Sixteen healthy individuals previously studied with EEG served as a control group. All EEGs were reviewed by 2 independent Neurophysiologists. EEG recordings were abnormal in 12/17 (71%) in the LQTS group, while abnormalities were present in only 2/16 (13%) of healthy controls (p<0.01). In the LQTS group, all abnormal EEGs showed a combination of theta activity and sharp waves. Two patients showed additional delta activity. None of the patients had definite epileptic activity (spikes, spike-waves). Abnormal electrical cerebral activity was identified more frequently in subjects with LQTS secondary to a potassium channel mutation compared to healthy controls. This result indicates a possible link between cardiac and cerebral channelopathy.
    Heart rhythm: the official journal of the Heart Rhythm Society 09/2013; 10(12). DOI:10.1016/j.hrthm.2013.09.070 · 5.08 Impact Factor
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    ABSTRACT: The aim of the study was to investigate immunoglobulin levels in patients with epilepsy using the antiepileptic drugs (AED) levetiracetam (LEV), carbamazepine (CBZ), or lamotrigine (LTG). A total of 211 patients and 80 controls (age: 18-45 years) of both genders were included. The patients had been treated with either LEV (n = 47), CBZ (n = 90), or LTG (n = 74) monotherapy for at least 6 months. Total concentrations of immunoglobulin G (IgG), IgG subclasses (IgG1, IgG2, IgG3, and IgG4), immunoglobulin A (IgA), and immunoglobulin M (IgM) were measured. Smoking, drinking habits, and physical activity were recorded, and body mass index (BMI) was calculated. A significantly lower total IgG and IgG1 was found in both men and women treated with LTG and in men on CBZ. IgG2 and IgG4 were also lower in LTG-treated women, and IgA and IgM were lower in LTG-treated men. Patients treated with LEV did not differ from the control group. Low levels of immunoglobulins were found in patients with epilepsy treated with LTG or CBZ. As our group of patients consisted of otherwise healthy young adults, one should be especially aware of a possible effect of AEDs on immunoglobulin levels when treating selected patient groups, for example immunocompromised patients. Immunoglobulin concentrations should be measured in patients treated with LTG or CBZ who experience recurrent infections, and a change in medication should be considered.
    Acta neurologica Scandinavica. Supplementum 01/2013; 127(196):11-5. DOI:10.1111/ane.12044

Publication Stats

2k Citations
263.97 Total Impact Points


  • 2008–2015
    • Oslo University Hospital
      • • Department of Microbiology
      • • Department of Neurology
      Kristiania (historical), Oslo, Norway
    • Sykehuset Østfold
      Frederikstad, Østfold, Norway
    • Stavanger University Hospital
      • Department of Neurology
      Stavanger, Rogaland Fylke, Norway
  • 1986–2015
    • University of Oslo
      • • Faculty of Medicine
      • • Department of Neurology (NEUR)
      Kristiania (historical), Oslo, Norway
  • 2001
    • HfH – University of Applied Sciences of Special Needs Education
      Zürich, Zurich, Switzerland
  • 2000
    • Norwegian School of Veterinary Science
      Kristiania (historical), Oslo, Norway
  • 1993
    • Miami Children's Hospital
      Miami, Florida, United States