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  • 1. Asztely, F.
    et al.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    The diagnosis and treatment of limbic encephalitis2012In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 126, no 6, p. 365-375Article, review/survey (Refereed)
    Abstract [en]

    The term limbic encephalitis (LE) was first introduced in 1968. While this disease was initially considered rare and is often fatal with very few treatment options, several reports published in the last decade provide a better description of this condition as well as possible causes and some cases of successful treatment. The clinical manifestation of LE is primarily defined by the subacute onset of short-term memory loss, seizures, confusion and psychiatric symptoms suggesting the involvement of the limbic system. In addition, EEG often shows focal or generalized slow wave or epileptiform activity, and MRI findings reveal hyperintense signals of the medial temporal lobes in T2-weighted or FLAIR images. The current literature suggests that LE is not a single disorder but is comprised of a group of autoimmune disorders predominantly affecting the limbic system. Before the diagnosis of LE can be determined, other causes of subacute encephalopathy must be excluded, especially those resulting from infectious aetiologies. LE has previously been regarded as a paraneoplastic phenomenon associated with the classical onconeuronal antibodies that are primarily directed against intracellular antigens. However, recent literature suggests that LE is also associated with antibodies that are directed against cell surface antigens, and these cases of LE display a much weaker association to the neoplasm. The treatment options for LE largely depend on the aetiology of the disease and involve the removal of the primary neoplasm. Therefore, a search for the underlying tumour is mandatory. In addition, immunotherapy has been successful in a significant number of patients where LE is not associated with cancer.

  • 2.
    Bajic, Dragan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wang, Cheng
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Mattsson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Lundberg, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Eeg-Olofsson, Orvar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Incomplete inversion of the hippocampus: a common developmental anomaly2008In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 18, no 1, p. 138-142Article in journal (Refereed)
    Abstract [en]

    Incomplete inversion of the hippocampus, an imperfect fetal development, has been described in patients with epilepsy or severe midline malformations. We studied this condition in a nonepileptic population without obvious developmental anomalies. We analyzed the coronal MR images of 50 women and 50 men who did not have epilepsy. Twenty of them were healthy volunteers and 80 were patients without obvious intracranial developmental anomalies, intracranial masses, hydrocephalus or any condition affecting the temporal lobes. If the entire hippocampus (the head could not be evaluated) were affected, the incomplete inversion was classified as total, otherwise as partial. Incomplete inversion of the hippocampus was found in 19/100 subjects (9 women, 10 men). It was unilateral, always on the left side, in 13 subjects (4 women, 9 men): 9 were of the total type, 4 were partial. It was bilateral in six subjects (five women, one man): four subjects had total types bilaterally, two had a combination of total and partial types. The collateral sulcus was vertically oriented in all subjects with a deviating hippocampal shape. We conclude that incomplete inversion of the hippocampus is not an unusual morphologic variety in a nonepileptic population without other obvious intracranial developmental anomalies.

  • 3.
    Dagiasi, Loanna
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden;NAL Hosp Trollhattan, Trollhattan, Sweden.
    Vall, Victor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zelano, Johan
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Treatment of epilepsy in multiple sclerosis2018In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 58, p. 47-51Article in journal (Refereed)
    Abstract [en]

    Purpose: The prevalence of epilepsy is increased in multiple sclerosis (MS), but information on AED treatment and seizure outcome is scarce. We describe epilepsy characteristics including the use of AEDs and proportion of seizure-free patients at two tertiary hospitals in Sweden. Method: We retrospectively studied electronic medical records of all patients with a diagnosis of MS and seizures at Sahlgrenska university hospital and Uppsala university hospital. Clinical data were reviewed until 2017. Results: We identified a total of 62 MS patients with at least one seizure. Median age at the first seizure (before or after MS) was 41 years (range 0-80). The most common MS disease course at the first seizure was secondary progressive MS, the neurological disability was considerable, and most patients had several MRI lesions at their first seizure. The first EEG demonstrated epileptiform discharges in 38% and unspecific pathology in 40%. Current seizure status could be determined for 37 patients. Out of these, 46% had been seizure free for more than one year at last follow-up. The majority of patients (65%) were on monotherapy at last follow-up. Carbamazepine was the most commonly used first AED, with a retention rate of 52%. No individual AED was associated with a particularly high rate of seizure freedom. The most common reason for discontinuation of the first AED was side-effects. Conclusion: Seizure freedom rates were low, perhaps indicating a need for higher ambitions in management. Side effects of AEDs may be a particular concern when treating epilepsy in patients with MS.

  • 4.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Relative Cerbral Blood Flow Measurement using dynamic Flumazenil-PET may Replace Fluorodeoxyglucose-PET in Epilepsy Surgical Investigations2012Article in journal (Other academic)
  • 5.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Linnman, Clas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Increased neurokinin-1 receptor availability in temporal lobe epilepsy: A positron emission tomography study using [(11)C]GR2051712011In: Epilepsy Research, ISSN 0920-1211, E-ISSN 1872-6844, Vol. 97, no 1-2, p. 183-189Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Activation of the neurokinin-1 (NK1) receptor by neuropeptide substance P (SP) induces and maintains epileptic activity in various experimental models of epilepsy. The primary objective of this study was to investigate whether neurobiological changes linked to NK1-SP receptor system are associated with hyperexcitability in patients with temporal lobe epilepsy (TLE). A secondary objective was to investigate the relationship between seizure frequency and NK1 receptor availability.

    METHODS: A positron emission tomography study was conducted with the selective NK1 receptor antagonist [(11)C]GR205171 in nine patients with TLE and 18 healthy control participants. Parametric PET images were generated using the Patlak graphical method, with cerebellum as reference region. Data analyses including group comparisons were performed using statistical parametric mapping.

    RESULTS: Patients with TLE showed increased NK1 receptor availability in both hemispheres with the most pronounced increase in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptor availability and seizure frequency was observed in the medial temporal lobe and in the lentiform nucleus ipsilateral to the seizure onset.

    CONCLUSION: Our results suggest that there is an intrinsic network using the NK1-SP receptor system for synaptic transmission and epileptiform activity in TLE.

  • 6. Edelvik, Anna
    et al.
    Rydenhag, Bertil
    Olsson, Ingrid
    Flink, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kallen, Kristina
    Malmgren, Kristina
    Long-term outcomes of epilepsy surgery in Sweden A national prospective and longitudinal study2013In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 81, no 14, p. 1244-1251Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate prospective, population-based long-term outcomes concerning seizures and antiepileptic drug (AED) treatment after resective epilepsy surgery in Sweden. Methods: Ten-and 5-year follow-ups were performed in 2005 to 2007 for 278/327 patients after resective epilepsy surgery from 1995 to 1997 and 2000 to 2002, respectively. All patients had been prospectively followed in the Swedish National Epilepsy Surgery Register. Ninety-three patients, who were presurgically evaluated but not operated, served as controls. Results: In the long term (mean 7.6 years), 62% of operated adults and 50% of operated children were seizure-free, compared to 14% of nonoperated adults (p < 0.001) and 38% of nonoperated children (not significant). Forty-one percent of operated adults and 44% of operated children had sustained seizure freedom since surgery, compared to none of the controls (p < 0.0005). Multivariate analysis identified >= 30 seizures/month at baseline and long epilepsy duration as negative predictors and positive MRI to be a positive predictor of long-term seizure-free outcome. Ten years after surgery, 86% of seizure-free children and 43% of seizure-free adults had stopped AEDs in the surgery groups compared to none of the controls (p < 0.0005). Conclusions: This population-based, prospective study shows good long-term seizure outcomes after resective epilepsy surgery. The majority of the patients who are seizure-free after 5 and 10 years have sustained seizure freedom since surgery. Many patients who gain seizure freedom can successfully discontinue AEDs, more often children than adults. Classification of evidence: This study provides Class III evidence that more patients are seizure-free and have stopped AED treatment in the long term after resective epilepsy surgery than nonoperated epilepsy patients.

  • 7.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lindskog, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engström, Mathias
    GE Healthcare, Stockholm, Sweden..
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Correlation between regional cerebral blood flow based on simultaneously acquired arterial spin labelling MRI and 15O-water-PET using zero-echo-time-based attenuation correction2017In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, article id 362Article in journal (Other academic)
    Abstract [en]

    Objectives: Arterial spin labelling (ASL) MRI promises clinical value in several common neurological disorders. Its quantitative accuracy and reproducibility, however, need to be further validated, ideally using simultaneously acquired measurements with 15O-water-PET on an integrated PET-MR scanner. However, so far, few studies have attempted this and the inclusion of bone in MR-based attenuation correction for PET has thus far been a challenge, compromising the quantitative accuracy of PET-MR based 15O-water PET data. The aim of the present work was to assess the correlation of ASL- and 15O-water-PET based regional cerebral blood flow (rCBF) values based on simultaneously acquired data, using zero-echo-time (ZTE)-based attenuation correction, as well as to assess the reproducibility of ASL-based rCBF.

    Methods: Six subjects underwent 10 min PET scans after automated bolus injection of 400 MBq 15O-water (1 mL/s during 5 s followed by 35 mL saline at 2 mL/s) on a time-of-flight integrated PET-MR scanner (Signa PET-MR, GE Healthcare). Arterial blood radioactivity concentrations were monitored using continuous sampling from the radial artery (Swisstrace Twilite Two). Simultaneously, a 3D FSE pseudo-continuous ASL (3D pCASL) with a spiral read-out as supplied by the scanner manufacturer in the commercial software were acquired using an 8 channel head coil (Invivo Hi-Res Head Coil). In addition, 3D T1-w, ZTE and Dixon fat-water MRI were acquired. The ASL procedure was repeated after 2 h (patients remained in the scanner). Quantifiable ASL-based CBF maps were generated. PET images were reconstructed into 26 frames of increasing durations using time-of-flight OSEM (2 iterations, 28 subsets) and a 5 mm post-filter, with ZTE-based attenuation correction. Blood sampler data were corrected for delay and dispersion and 15O-water-based CBF maps were calculated using a basis function implementation of the single tissue compartment model including a fitted blood volume parameter. CBF maps were co-registered to each patient's T1-w image. 3D T1-w images were segmented and normalised to MNI space using SPM12, and anterior, middle and posterior flow territory volumes of interest (VOIs) were created from a standard template in MNI space and inversely transformed for each patient. In addition, a 45-VOI probabilistic template was applied using PVElab software. Correlations between PET- and ASL-based rCBF values were assessed using regression analysis, and reproducibility of ASL using a paired t-test.

    Results: Mean (CI) total brain grey matter CBF values were 67.2 (48.0-86.5) mL/min/100 g for 15O-water-PET and 65.5 (55.7-75.5) mL/min/100 g for ASL. Although correlation and agreement between 15O-water and ASL-based rCBF for individual VOIs in the 45-VOI template were generally poor, significant correlations were found on a grey matter flow territory basis, with R2 ranging from 0.70 in the anterior flow territory to 0.86 in the middle flow territory. rCBF values were significantly reduced between second and first ASL for all flow territories (p<0.01), with a mean decrease of 10%.

    Conclusion: A good correlation between regional flow territory CBF values based on ASL and 15O-water-PET was found, using ZTE-based attenuation correction for PET data which takes bone tissue into account. ASL values for regional flow territories may have potential applications in patients with dementia or cerebrovascular diseases affecting blood flow such as moya moya. The decrease of ASL-based rCBF values in the reproducibility study needs to be investigated further to assess whether this is a methodological issue or reflects a true decrease in rCBF. Research Support: Uppsala County Council

  • 8.
    Halawa, Imad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Vlachogiannis, Pavlos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Amandusson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Elf, Kristin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Zetterberg, H.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden.;UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Seizures, CSF neurofilament light and tau in patients with subarachnoid haemorrhage2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 137, no 2, p. 199-203Article in journal (Refereed)
    Abstract [en]

    Objectives

    Patients with severe subarachnoid haemorrhage (SAH) often suffer from complications with delayed cerebral ischaemia (DCI) due to vasospasm that is difficult to identify by clinical examination. The purpose of this study was to monitor seizures and to measure cerebrospinal fluid (CSF) concentrations of neurofilament light (NFL) and tau, and to see whether they could be used for predicting preclinical DCI.

    Methods

    We prospectively studied 19 patients with aneurysmal SAH who underwent treatment with endovascular coiling. The patients were monitored with continuous EEG (cEEG) and received external ventricular drainage (EVD). CSF samples of neurofilament light (NLF) and total tau (T-tau) protein were collected at day 4 and day 10. Cox regression analysis was applied to evaluate whether seizures and protein biomarkers were associated with DCI and poor outcome.

    Results

    Seven patients developed DCI (37%), and 4 patients (21%) died within the first 2months. Six patients (32%) had clinical seizures, and electrographic seizures were noted in one additional patient (4.5%). Increased tau ratio (proportion tau10/tau4) was significantly associated with DCI and hazard ratio [HR=1.33, 95% confidence interval (CI) 1.055-1.680. P=.016].

    Conclusion

    Acute symptomatic seizures are common in SAH, but their presence is not predictive of DCI. High values of the tau ratio in the CSF may be associated with development of DCI.

  • 9.
    Halawa, Imad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zelano, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Hypoglycaemia and Risk of Seizures: a Retrospective Cross-Sectional Study2014In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 55, p. 231-231Article in journal (Other academic)
  • 10.
    Halawa, Imad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zelano, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Hypoglycemia and risk of seizures: A retrospective cross-sectional study2015In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 25, p. 147-149Article in journal (Refereed)
    Abstract [en]

    Purpose: Few studies have been dedicated to assess neurological symptoms in relations to hypoglycemia. In this study we investigated the association between different levels of hypoglycemia and the occurrence of epileptic seizures in patients without a prior diagnosis of epilepsy. Method: A retrospective cross-sectional study. Results: We identified 388 individuals from a laboratory database in Swedish regional hospital who had been found to have a glucose value of <= 3.5 mM between January and December 2009. Medical records were reviewed. Hypoglycemia was defined at three different categories: 0-2 mM (40 patients), 2.1-3 mM (154 patients) and 3.1-3.5 mM (194 patients). 14 patients had disturbance of consciousness including 3 with seizures. The majority of cases had coma, a generalized tonic-clonic seizure was seen only when s-glucose dropped below 2.0 mM. Two cases with focal seizure were noted, one at s-glucose 2.0 mM, and one at s-glucose 3.3 mM. The absolute risks (95% confidence interval) for having major neurological symptoms at glucose levels of <= 2.0 mM were 0.25 (0.13-0.41), 0.02 (0-0.06) at 2.1-3.0 mM and 0.01 (0-0.03) at 3.1-3.5 mM. Conclusion: Coma is the most common neurological symptom related to hypoglycemia. Epileptic seizures are rare and not as common as previously assumed. 

  • 11.
    Hansen, Julia
    et al.
    Univ Gothenburg, Dept Neurol, Sahlgrenska Univ Hosp, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden..
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zelano, Johan
    Univ Gothenburg, Dept Neurol, Sahlgrenska Univ Hosp, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden..
    Cause of death in patients with poststroke epilepsy: Results from a nationwide cohort study2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, article id e0174659Article in journal (Refereed)
    Abstract [en]

    The risk of death is increased for persons with epilepsy. The literature on causes of death in epilepsy is based mainly on cohorts with epilepsy of mixed aetiologies. For clinical purposes and improved understanding of mortality in different epilepsies, more information is needed on mortality in epilepsies of specific causes. In poststroke epilepsy (PSE), seizures occur in a setting of vascular disease and high mortality rates. The extent to which epilepsy contributes to mortality in this patient group is poorly understood. We therefore aimed to describe causes of death (COD) in PSE on a national scale. A previously identified cohort of 7740 patients with epilepsy or seizures after a stroke in 2005-2010 was investigated. A total of 4167 deaths occurred before the end of 2014. The standardized mortality ratio for the study cohort was 3.56 (95% CI: 3.45-3.67). The main underlying causes of death were disorders of the circulatory system (60%) followed by neoplasms (12%). Diseases of the nervous system were the sixth leading underlying COD (3%), and epilepsy or status epilepticus was considered the underlying COD in approximately a similar proportion of cases as neurodegenerative disorders (0.9% and 1.1%, respectively). Epilepsy was considered a contributing COD in 14% of cases. Our findings highlight the importance of optimal management of vascular morbidity in patients with PSE. The large proportion of patients with epilepsy as a contributing COD indicate the need of high ambitions also regarding the management of seizures in patients with PSE.

  • 12.
    Knight, A
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Pauksen, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eva, Kumlien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Fatal outcome of tick-borne encephalitis in two patients with rheumatic disease treated with rituximab.2017In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56, no 5, p. 855-856Article in journal (Refereed)
  • 13. Kors, E. E.
    et al.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Vanmolkot, K. R.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Haan, Jan
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Flink, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Ginjaar, H.B.
    Frants, R.R.
    Ferrari, M.D.
    van den Maagdenberg, A. M.
    Childhood, epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new CACNA1A mutation2004In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 63, no 6, p. 1136-1137Article in journal (Refereed)
  • 14.
    Kumlien, Eva
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurologi.
    Ben-Menachem, Elinor
    Epilepsi - nya möjligheter för behandling och diagnostik2004In: Incitament, p. 21-23Article, review/survey (Other (popular scientific, debate etc.))
  • 15.
    Kumlien, Eva
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry.
    Nilsson, A
    Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry.
    Hagberg, G
    Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry.
    Langstrom, B
    Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry.
    Bergstrom, M
    Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry.
    PET with 11C-deuterium-deprenyl and 18F-FDG in focal epilepsy2001In: Acta Neurologica Scandinavica, Vol. 103, p. 360-Article in journal (Refereed)
  • 16.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Gaging, Johannes
    Uppsala Univ, Uppsala, Sweden..
    Lindskog, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Tracer kinetic analysis of the SV2A ligand 11C-UCBA as a PET marker for synaptic density in humans2017In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, article id 631Article in journal (Other academic)
    Abstract [en]

    Objectives: Quantitative imaging of the synaptic vesicle glycoprotein 2A (SV2A) with PET can be used as a measure of synaptic density in the human brain (Finnema et al, Science Tr Med 2016), changes of which occur in many neurodegenerative diseases. 11C-UCBA has previously been validated as an SV2A tracer in pigs (Estrada et al, Nucl Med Biol 2016), showing dose-dependent blocking and reversible binding. The aim of the present work was to evaluate tracer kinetic models and simplified methods for quantification of synaptic density using 11C-UCBA in humans.

    Methods: Eight subjects (6 epilepsy patients, 2 controls) underwent 90 min PET scans starting with injection of 5 MBq/kg 11C-UCBA on a time-of-flight integrated PET-MR scanner (Signa PET-MR, GE Healthcare). Arterial blood was withdrawn for measurements of whole blood and plasma concentrations and metabolite analysis. Images were reconstructed using zero-echo-time MR-based attenuation correction, accounting for bone attenuation. A probabilistic VOI template was defined on a T1-MRI image, acquired during the PET scan, and transferred to the dynamic PET images. A centrum semiovale VOI was drawn as potential reference tissue. Data were analysed using single-tissue (1T2k), two-tissue irreversible (2T3k) and reversible (2T4k) models, as well as the simplified reference tissue model (SRTM) and plasma- and reference-Logan methods, resulting in total distribution volume (VT) and binding potential (BPND) values, with binding potential both estimated directly and as distribution volume ratio to centrum semiovale (DVR). The optimal compartment model was determined using the Akaike information criterion (AIC). Standardized uptake value ratios (SUVR) at various time points were compared to modelling outcomes using regression analysis.

    Results: Plasma and brain kinetics of 11C-UCBA were slow, with peak activity in brain at 70-80 min. Parent fraction was approximately 50% at 90 min. Plasma-input data were best described using the 2T4k model, but this could often not provide robust VT or BPND values. Mean plasma-Logan VT was 24±17. Plasma-Logan DVR using centrum semiovale as reference tissue correlated well with 2T4k DVR (R2 0.94) for those regions where robust DVR values could be determined. Reference-Logan DVR showed good correlation with plasma-Logan DVR (R2 0.72). Plasma-Logan DVR-1 and SUVR-1 images are shown in Figure 1. SUVR for the 40-60 and 70-90 min intervals correlated well with reference-Logan DVR (R2 0.92 and 0.98).

    Conclusion: Slow kinetics of 11C-UCBA resulted in poor robustness of outcome parameters of reversible compartment models. However, reference-Logan DVR correlated well with plasma-Logan DVR. SUVR at 70-90 min p.i. correlated well with DVR and may be used as a simplified measure of synaptic density using 11C-UCBA. Research Support: Uppsala County Council

  • 17.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Phys..
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Imaging Ctr..
    Lindskog, K.
    Uppsala Univ Hosp, Med Phys..
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Imaging Ctr..
    Sprycha, M.
    Uppsala Univ Hosp, Med Imaging Ctr..
    Daging, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala Univ Hosp, Neurol..
    Eriksson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry. Uppsala Univ Hosp, Med Imaging Ctr..
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Imaging Ctr..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala Univ Hosp, Neurol..
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging. Uppsala Univ Hosp, Med Imaging Ctr..
    Quantitative assessment of synaptic density using the SV2A ligand C-11-UCBA in humans2017In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, p. 74-74Article in journal (Other academic)
  • 18.
    Malmgren, K.
    et al.
    Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Rydenhag, B.
    Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Olsson, I.
    Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Paediat, Gothenburg, Sweden..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Mattsson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Flink, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Epilepsy Surgery Trends In Sweden 1990-20132015In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 56, p. 145-145Article in journal (Other academic)
  • 19.
    Mattsson, Peter
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Tibblin, Bodil
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. rehab medicin.
    Kihlgren, Margareta
    Department of Women's and Children's Health.
    Kumlien, Eva
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    A prospective study of anxiety with respect to seizure outcome after epilepsy surgery2005In: Seizure, Vol. 14, p. 40-45Article in journal (Refereed)
  • 20. Persson, H.
    et al.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Ericson, M.
    Tomson, Torbjörn
    No apparent effect of surgery for temporal lobe epilepsy in heart rate variability2006In: Epilepsy Research, ISSN 0920-1211, E-ISSN 1872-6844, Vol. 70, no 2-3, p. 127-132Article in journal (Refereed)
    Abstract [en]

    Background: Impaired cardiac autonomic function may contribute to the risk of sudden unexpected death in epilepsy (SUDEP). Clinical observations indicate that successful epilepsy surgery is associated with a reduced risk of SUDEP. However, in a previous study we found impaired cardiac control pre-surgically in patients with poor outcome of surgery, indicating an a priori lower risk in responders to epilepsy surgery. We have now examined the effect of surgery on cardiac autonomic control in the same patients.

    Methods: We used 24 h EKG recordings to assess heart rate variability (HRV) by spectral analysis in 21 consecutive patients after temporal lobe epilepsy surgery. The HRV was compared with healthy controls, with pre-surgical HRV in the same patients, and analyzed in relation to seizure control 1 year after surgery.

    Results: The patients with poor outcome after surgery had significantly lower SD of RR-intervals, total power, very low frequency power and low frequency power than matched healthy controls. The patients with favorable outcome did not differ from the controls, and the postoperative HRV was not different from HRV before surgery in any of the patient groups.

    Conclusion: We could not demonstrate any effect on HRV of temporal lobe epilepsy surgery in these patients. The observed lower HRV in the poor outcome group was present already before epilepsy surgery as previously reported. Although our results need confirmation in a larger study, the observations suggest that the increased risk of SUDEP in patients failing epilepsy surgery may be due to a common factor predisposing to surgical failure, impaired HRV as well as to an increased risk of SUDEP.

  • 21. Persson, H
    et al.
    Kumlien, Eva
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Ericson, M
    Tomson, Torbjörn
    Preoperative heart rate variability in relation to surgery outcome in refractory epilepsy2005In: Neurology, Vol. 65, p. 1021-1025Article in journal (Refereed)
  • 22. Persson, Håkan
    et al.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Ericson, Mats
    Tomson, Torbjörn
    Circadian variation in heart-rate variability in localization-related epilepsy2007In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 48, no 5, p. 917-922Article in journal (Refereed)
    Abstract [en]

    Purpose: Case-control studies of sudden unexpected death in epilepsy (SUDEP) have reported that SUDEP is more likely to occur during sleep and thus presumably during night hours. The circadian variation of heart-rate variability (HRV) might be of relevance to this risk. We examined night versus daytime HRV in patients with newly diagnosed and refractory localization-related epilepsy, assessing the effects of drug treatment and epilepsy surgery on the night/daytime HRV ratio. Methods: We used spectral analysis to assess HRV and calculated the night-time (00.00-05.00)/daytime (07.30-21.30) ratio of HRV in 14 patients with newly diagnosed localization-related epilepsy before and during carbamazepine (CBZ) treatment and in 21 patients with temporal lobe epilepsy before and after epilepsy surgery. Both groups were compared with age- and sex-matched controls. Results: No significant differences were found from controls in the night/daytime ratios of HRV whether compared before or after initiation of treatment with CBZ in newly diagnosed epilepsy patients. When patients were used as their own controls, night/daytime ratios of standard deviation of RR intervals (p = 0.04) and total power (p = 0.04) were significantly lower during treatment than before. Compared with those of controls, the night/daytime ratios were lower in epilepsy surgery patients before surgery [low-frequency power (p = 0.04); high-frequency power (p = 0.04)]. Night/daytime ratios did not change significantly after surgery. Conclusions: The HRV of the patients was more affected during night-time when the risk of SUDEP seems to be highest in such patients.

  • 23.
    Sauro, K.
    et al.
    Univ Calgary, Clin Neurosci, Calgary, AB, Canada.;Univ Calgary, Community Hlth Sci, Calgary, AB, Canada..
    Wiebe, S.
    Univ Calgary, Clin Neurosci, Calgary, AB, Canada..
    Pedley, T.
    Columbia Univ, Neurol, New York, NY USA..
    Dunkley, C.
    Kings Mill Hosp, Pediat, Sutton In Ashfield, England..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Moshe, S.
    Albert Einstein Coll Med, Neurol, Bronx, NY 10467 USA.;Albert Einstein Coll Med, Pediat, Bronx, NY 10467 USA..
    Nakasato, N.
    Tohoku Univ, Sch Med, Epileptol, Seiryo, Japan..
    Perucca, E.
    Univ Pavia, Internal Med & Therapeut, I-27100 Pavia, Italy..
    Senties, H.
    Med Sur Consultorio, Neurol, Madero, Mexico..
    Thomas, S.
    Sree Chitra Tirunal Inst Med Sci & Technol, Dept Neurol, Trivandrum, Kerala, India..
    Wang, Y.
    Xuan Wu Hosp, Neurol, Beijing, Peoples R China..
    Wilmshurst, J.
    Univ Cape Town, Red Cross War Mem Childrens Hosp, Paediat, ZA-7925 Cape Town, South Africa..
    Jette, N.
    Univ Calgary, Clin Neurosci, Calgary, AB, Canada.;Univ Calgary, Community Hlth Sci, Calgary, AB, Canada..
    Current State Of International Epilepsy Guidelines2015In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 56, p. 238-238Article in journal (Other academic)
  • 24.
    Sauro, Khara M.
    et al.
    Univ Calgary, Cumming Sch Med, Dept Clin Neurosci, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Dept Community Hlth Sci, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, OBrien Inst Publ Hlth, Calgary, AB, Canada..
    Wiebe, Samuel
    Univ Calgary, Cumming Sch Med, Dept Clin Neurosci, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Dept Community Hlth Sci, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, OBrien Inst Publ Hlth, Calgary, AB, Canada..
    Dunkley, Colin
    Kings Mill Hosp, Dept Paediat, Sutton In Ashfield, Notts, England..
    Janszky, Jozsef
    Univ Pecs, Dept Neurol, Pecs, Hungary..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Moshe, Solomon
    Albert Einstein Coll Med, Saul R Korey Dept Neurol, Dominick P Purpura Dept Neurosci, Montefiore Einstein Epilepsy Management Ctr, Bronx, NY 10467 USA.;Albert Einstein Coll Med, Dept Pediat, Lab Dev Epilepsy, Montefiore Einstein Epilepsy Management Ctr, Bronx, NY 10467 USA.;Montefiore Med Ctr, Bronx, NY 10467 USA..
    Nakasato, Nobukazu
    Tohoku Univ, Dept Epileptol, Sch Med, Tohoku, Japan..
    Pedley, Timothy A.
    Columbia Univ, Med Ctr, Neurol Inst New York, Dept Neurol, New York, NY USA..
    Perucca, Emilio
    Univ Pavia, Dept Internal Med Therapeut, Unit Clin & Expt Pharmacol, I-27100 Pavia, Italy.;C Mondino Natl Neurol Inst, Pavia, Italy..
    Senties, Horacio
    Natl Inst Med Sci & Nutr Salvador Zubiran, Dept Neurol & Psychiat, Mexico City, DF, Mexico..
    Thomas, Sanjeev V.
    Sree Chitra Tirunal Inst Med Sci & Technol, Dept Neurol, Trivandrum, Kerala, India..
    Wang, Yuping
    Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing, Peoples R China..
    Wilmshurst, Jo
    Univ Cape Town, Red Cross War Mem Childrens Hosp, Dept Pediat Neurol, ZA-7925 Cape Town, South Africa..
    Jette, Nathalie
    Univ Calgary, Cumming Sch Med, Dept Clin Neurosci, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, Dept Community Hlth Sci, Calgary, AB, Canada.;Univ Calgary, Cumming Sch Med, OBrien Inst Publ Hlth, Calgary, AB, Canada..
    The current state of epilepsy guidelines: A systematic review2016In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 57, no 1, p. 13-23Article, review/survey (Refereed)
    Abstract [en]

    Objective: The International League Against Epilepsy (ILAE) Epilepsy Guidelines Task Force, composed of 14 international members, was established in 2011 to identify, using systematic review methodology, international epilepsy clinical care guidelines, assess their quality, and determine gaps in areas of need of development. Methods: A systematic review of the literature (1985-2014) was performed in six electronic databases (e.g. Medline, Embase) using a broad search strategy without initial limits to language or study design. Six gray literature databases (e.g., American Academy of Neurology [AAN], ILAE) were also searched to minimize publication bias. Two independent reviewers screened abstracts, reviewed full text articles, and performed data abstraction. Descriptive statistics and a meta-analysis were generated. Results: The search identified 10,926 abstracts. Of the 410 articles selected for full text review, 63 met our eligibility criteria for a guideline. Of those included, 54 were in English and 9 were in other languages (French, Spanish, and Italian). Of all guidelines, 29% did not specify the target age groups, 27% were focused on adults, 22% included only children, and 6% specifically addressed issues related to women with epilepsy. Guidelines included in the review were most often aimed at guiding clinical practice for status epilepticus (n = 7), first seizure (n = 6), drug-resistant epilepsy (n = 5), and febrile seizures (n = 4), among others. Most of the guidelines were therapeutic (n = 35) or diagnostic (n = 16) in nature. The quality of the guidelines using a 1-7 point scale (7 = highest) varied and was moderate overall (mean = 4.99 +/- 1.05 [SD]). Significance: We identified substantial gaps in topics (e.g., epilepsy in the elderly) and there was considerable heterogeneity in methodologic quality. The findings should offer a valuable resource for health professionals caring for people with epilepsy, since they will help guide the prioritization, development, and dissemination of future epilepsy-related guidelines.

  • 25.
    Smits, Anja
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Andsberg, Gunnar
    Andersen, Peter M
    Andersson, Magnnus
    Gunnarsson, Martin
    Kumlien, Eva
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Lycke, Jan
    Marup Jensen, Svend
    Nilsson Remahl, Ingela
    Nyholm, Dag
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Neurologi i förvandling - från diagnostik till terapeutisk disciplin2008In: Läkartidningen, Vol. 105, p. 2413-2416Article in journal (Other scientific)
  • 26.
    Zelano, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Halawa, Imad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Hyponatremia augments kainic-acid induced status epilepticus in the mouse: A model for dysmetabolic status epilepticus2013In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 54, no SI, p. 106-106Article in journal (Other academic)
  • 27.
    Zelano, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Halawa, Imad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Hyponatremia augments kainic-acid induced status epilepticus in the mouse: A model for dysmetabolic status epilepticus2013In: Epilepsy Research, ISSN 0920-1211, E-ISSN 1872-6844, Vol. 106, no 1-2, p. 29-34Article in journal (Refereed)
    Abstract [en]

    Status epilepticus (SE) is a dreaded neurological emergency. A reignited interest in SE has resulted in a more adaptive use of treatment protocols. More knowledge on SE of various aetiologies is therefore needed. We are interested in treatment of SE under hyponatremia, and have here evaluated whether SE induced by systemic kainic acid could be a suitable platform for such studies. Acute hyponatremia was induced in C57/BL6 mice by intraperitoneal injection of dDAVP and water loading. Hyponatremic mice displayed an increased frequency of epileptiform spikes on EEG and 5/9 hyponatremic mice displayed electrographic seizures. After kainic acid (20mg/kg) treatment, hyponatremic mice displayed significantly longer time with electrographic seizure activity, which was also seen after treatment with diazepam (20mg/kg). We conclude that hyponatremia augments kainic acid-induced SE, This model might be a valuable platform for studies on treatment of SE in hyponatremia.

  • 28.
    Zelano, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Levetiracetam as alternative stage two antiepileptic drug in status epilepticus: A systematic review2012In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 21, no 4, p. 233-236Article, review/survey (Refereed)
    Abstract [en]

    Background: The role of new antiepileptic drugs (AED) in the treatment of status epilepticus (SE) is of interest, especially in benzodiazepine-resistant status epilepticus where phenytoin is deemed inappropriate due to allergy or comorbidity. Levetiracetam (LEV) is a new AED with few side effects. It is easy to administer. Reports exist of its use in SE in adults.

    Aims: To clarify the evidence for use of LEV as an alternative stage two AED in treatment of SE by a systematic review of the literature.

    Method: An online MEDLINE search identified 118 articles. The abstracts were screened for studies written in English, in which (1) at least two adults had been treated, and (2) LEV had been administered intravenously as the first AED, on its own or together with benzodiazepines. Ten studies were included.

    Results: Out of the ten studies, seven were retrospective observational, two prospective observational, and one prospective randomized. The studies described a total of 334 patients. The most common reason for administrating LEV was that standard treatment was deemed inappropriate. The efficacy ranged from 44% to 94%, with higher efficacy reported in the retrospective studies.

    Conclusions: The evidence for use of LEV as an alternative stage two AED in SE is limited. The higher efficacy reported in retrospective studies indicates possible publication bias, and caution is advised when the results of these retrospective studies are considered in clinical decision-making.

  • 29.
    Zelano, Johan
    et al.
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Neurol, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden..
    Larsson, David
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Neurol, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Pre-stroke seizures: A nationwide register-based investigation2017In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 49, p. 25-29Article in journal (Refereed)
    Abstract [en]

    Purpose: The relationship between cerebroyascular disease and seizures is clearly illustrated by poststroke epilepsy. Seizures can also be the first manifestation of cerebrovascular disease and case control studies have demonstrated that seizures carry an increased risk of subsequent stroke. Thus, seizures could serve as a marker for vascular risk that merits intervention, but more data is needed before proper trials can be conducted. The occurrence of pre-stroke seizures has not been assessed on a national scale. We asked what proportion of strokes in middle-aged and elderly patients was preceded by seizures. Methods: All patients over 60 years of age with first-ever stroke in 2005-2010 (n = 92,596) were identified in the Swedish stroke register (Riksstroke) and cross-sectional data on a history of a first seizure or epilepsy diagnosis in the ten years preceding stroke were collected from national patient registers with mandatory reporting. Results: 1372 patients (1.48%) had a first seizure or epilepsy diagnosis registered less than ten years prior to the index stroke. The mean latency between seizure and stroke was 1474 days (SD 1029 days). Conclusions: Seizures or epilepsy preceded 1.48% of strokes in patients > 60 years of age. Based on recent national incidence figures, 5-20% of incident cases of seizures or epilepsy after 60 years of age could herald stroke, depending on age group. These proportions are of a magnitude that merit further study on how to reduce the risk of stroke in patients with late-onset seizures or epilepsy.

  • 30.
    Zelano, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lundberg, Rebecca Gertz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala Univ, Dept Neurosci, S-75185 Uppsala, Sweden..
    Baars, Leopold
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala Univ, Dept Neurosci, S-75185 Uppsala, Sweden..
    Hedegård, Emelie
    Uppsala Univ, Dept Neurosci, S-75185 Uppsala, Sweden..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala Univ, Dept Neurosci, S-75185 Uppsala, Sweden..
    Clinical course of poststroke epilepsy: a retrospective nested case-control study2015In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 5, no 9, article id e00366Article in journal (Refereed)
    Abstract [en]

    Introduction: Recently, several epidemiological studies have demonstrated that epilepsy develops after approximately 10% of all cerebrovascular lesions. With an aging population, poststroke epilepsy is likely to be of increasing relevance to neurologists and more knowledge on the condition is needed. Patients with poststroke epilepsy are likely to differ from other epilepsy patient populations regarding age, side-effect tolerability, comorbidities, and life expectancy, all of which are important aspects when counselling newly diagnosed patients to make informed treatment decisions. Method: We have here performed a nested case-control study on 36 patients with poststroke epilepsy and 55 controls that suffered stroke but did not develop epilepsy. The average follow-up time was between 3 and 4 years. Results: In our material, two-thirds of patients achieved seizure freedom and 25% experienced a prolonged seizure (status epilepticus) during the follow-up period. Cases consumed more health care following their stroke, but did not suffer more traumatic injuries. Interestingly, the mortality among cases and controls did not differ significantly. This observation needs to be confirmed in larger prospective studies, but indicate that poststroke epilepsy might not infer additional mortality in this patient group with considerable comorbidities. Conclusions: The observations presented can be of value in the counselling of patients, reducing the psychosocial impact of the diagnosis, and planning of future research on poststroke epilepsy.

  • 31.
    Zelano, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Moller, F.
    Dobesberger, J.
    Trinka, E.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Infections in Status Epilepticus: A Retrospective 5-Year Cohort Study2014In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 55, p. 37-38Article in journal (Other academic)
  • 32.
    Zelano, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Moller, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Dobesberger, Judith
    Trinka, Eugen
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Infections in status epilepticus: A retrospective 5-year cohort study2014In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 23, no 8, p. 603-606Article in journal (Refereed)
    Abstract [en]

    Purpose: Status epilepticus (SE) has attracted renewed interest lately, and efforts are made to optimize every treatment stage. For refractory SE, optimal supporting care involves mechanical ventilation and intensive care unit (ICU) admission. Infections often complicate SE and recently a single-centre observational study demonstrated an association between infections and poor short-term outcome of SE in a cohort of severely ill patients. We have here attempted to replicate those findings in a different cohort. Method: We performed a retrospective observational study and included all patients with a diagnosis of SE during 2008-2012 at a Swedish tertiary referral centre. Results: The cohort consisted of 103 patients (53% female, 47% male, median age 62 years, range 19-87 years). In house mortality was less than 2 and 70% of the patients' were discharged home. The most common aetiologies of SE were uncontrolled epilepsy (37%) and brain tumours (16%). A total of 39 patients suffered infections during their stay. Presence of infection was associated with mechanical ventilation (OR 3.344, 95% Cl 1.44-7.79) as well as not being discharged home (OR2.705, 95% Cl 1.14-6.44), and duration of SE was significantly longer in patients with infection (median 1 day vs. 2.5 days, p < 0.001). Conclusion: We conclude that the previously described association between infections, a longer SE duration, and an unfavourable outcome of SE seems valid also in SE of less severe aetiology.  

  • 33.
    Åhs, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Persson, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Medial temporal lobe resection attenuates superior temporal sulcus response to faces2014In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 61, p. 291-298Article in journal (Refereed)
    Abstract [en]

    Face perception depends on activation of a core face processing network including the fusiform face area, the occipital face area and the superior temporal sulcus (STS). The medial temporal lobe (MTL) is also involved in decoding facial expression and damage to the anterior MTL, including the amygdala, generally interferes with emotion recognition. The impairment in emotion recognition following anterior MTL injury can be a direct result from injured MTL circuitry, as well as an indirect result from decreased MTL modulation of areas in the core face network. To test whether the MTL modulates activity in the core face network, we used functional magnetic resonance imaging to investigate activation in the core face processing network in patients with right or left anterior temporal lobe resections (ATR) due to intractable epilepsy. We found reductions of face-related activation in the right STS after both right and left ATR together with impaired recognition of facial expressions. Reduced activity in the fusiform and the occipital face areas was also observed in patients after right ATR suggesting widespread effects on activity in the core face network in this group. The reduction in face-related STS activity after both right and left ATR suggests that MTL modulation of the STS may facilitate recognition of facial expression.

  • 34.
    Örlén, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Entesarian, Miriam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Söderberg, Per
    Department of Ophthalmology, Västerås Hospital.
    Påhlman, Magnus
    Darin, Niklas
    Kyllerman, Mårten
    Holmberg, Eva
    Engler, Henry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Dahl, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    SPG11 mutations cause Kjellin syndrome, a hereditary spastic paraplegia with thin corpus callosum and central retinal degeneration2009In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-4841, E-ISSN 1552-485X, Vol. 150B, no 7, p. 984-992Article in journal (Refereed)
    Abstract [en]

    Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is genetically heterogenous and approximately 35% of patients carry mutations in either of the SPG11 or SPG15 genes. Disease onset is during the first three decades of life with spastic paraplegia and mental impairment. Peripheral neuropathy and amyotrophy may occur. Kjellin syndrome is characterized by central retinal degeneration in addition to ARHSP-TCC and the disease is associated with mutations in the SPG15 gene. We identified five patients in four unrelated kindreds with spastic paraplegia and mental impairment. Magnetic resonance imaging revealed TCC, atrophy elsewhere in the brain and increased T2 signal intensity in the periventricular white matter. Probands from the four kindreds were screened for mutations in the SPG11 gene. All patients were found homozygous or compound heterozygous for truncating SPG11 mutations of which four are reported for the first time. Ophthalmological investigations revealed that the four index cases have central retinal degeneration consistent with Kjellin syndrome. PET examinations with N-[11C-methyl]-L-deuterodeprenyl (DED) and fluor-18 2-fluorodeoxyglucose (FDG) were performed in two patients with Kjellin syndrome. We observed a reduced glucose uptake in the thalami, anterior cingulum, and sensorimotor cortex indicating neuronal loss, and an increased DED binding in the thalami and pons which suggests astrogliosis. From our results we extend the SPG11 associated phenotype to comprise also Kjellin syndrome, previously found to be associated with mutations in the SPG15 gene. We anticipate that degeneration of the central retina is a common and previously unrecognized feature in SPG11 related disease.

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