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  • 1. Abdelhak, Ahmed
    et al.
    Barba, Lorenzo
    Romoli, Michele
    Benkert, Pascal
    Conversi, Francesco
    D'Anna, Lucio
    Masvekar, Ruturaj R
    Bielekova, Bibiana
    Prudencio, Mercedes
    Petrucelli, Leonard
    Meschia, James F
    Erben, Young
    Furlan, Roberto
    De Lorenzo, Rebecca
    Mandelli, Alessandra
    Sutter, Raoul
    Hert, Lisa
    Epple, Varenka
    Marastoni, Damiano
    Sellner, Johann
    Steinacker, Petra
    Aamodt, Anne Hege
    Heggelund, Lars
    Dyrhol-Riise, Anne Margarita
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Acquired brain injury.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Blennow, Kaj
    Zetterberg, Henrik
    Tumani, Hayrettin
    Sacco, Simona
    Green, Ari J
    Otto, Markus
    Kuhle, Jens
    Ornello, Raffaele
    Foschi, Matteo
    Abu-Rumeileh, Samir
    Prognostic performance of blood neurofilament light chain protein in hospitalized COVID-19 patients without major central nervous system manifestations: an individual participant data meta-analysis.2023In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 270, no 7, p. 3315-3328Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19).

    METHODS: We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL.

    RESULTS: We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively.

    CONCLUSIONS: Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.

  • 2. Ahl, Matilda
    et al.
    Taylor, Marie K.
    Avdic, Una
    Lundin, Anna
    Andersson, My
    Amandusson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Neurophysiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Compagno Strandberg, Maria
    Ekdahl, Christine T.
    Immune response in blood before and after epileptic and psychogenic non-epileptic seizures2023In: Heliyon, E-ISSN 2405-8440, Vol. 9, no 3, article id e13938Article in journal (Refereed)
    Abstract [en]

    Inflammatory processes may provoke epileptic seizures and seizures may promote an immune reaction. Hence, the systemic immune reaction is a tempting diagnostic and prognostic marker in epilepsy. We explored the immune response before and after epileptic and psychogenic non-epileptic seizures (PNES). Serum samples collected from patients with videoEEG-verified temporal or frontal lobe epilepsy (TLE or FLE) or TLE + PNES showed increased interleukin-6 (IL-6) levels in between seizures (interictally), compared to controls. Patients with PNES had no increase in IL-6. The IL-6 levels increased transiently even further within hours after a seizure (postictally) in TLE but not in FLE patients. The postictal to interictal ratio of additionally five immune factors were also increased in TLE patients only. We conclude that immune factors have the potential to be future biomarkers for epileptic seizures and that the heterogeneity among different epileptic and non-epileptic seizures may be disclosed in peripheral blood sampling independent of co-morbidities.

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  • 3. 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.

  • 4.
    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.

  • 5.
    Banote, Rakesh Kumar
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, SE-40530 Gothenburg, Sweden; Sahlgrens Univ Hosp, Dept Neurol, Gothenburg, Sweden.
    Larsson, David
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, SE-40530 Gothenburg, Sweden; Sahlgrens Univ Hosp, Dept Neurol, Gothenburg, Sweden.
    Berger, Evelin
    Univ Gothenburg, Sahlgrenska Acad, Prote Core Facil, Gothenburg, Sweden.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Zelano, Johan
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, SE-40530 Gothenburg, Sweden; Sahlgrens Univ Hosp, Dept Neurol, Gothenburg, Sweden; Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden.
    Quantitative proteomic analysis to identify differentially expressed proteins in patients with epilepsy2021In: Epilepsy Research, ISSN 0920-1211, E-ISSN 1872-6844, Vol. 174, article id 106674Article in journal (Refereed)
    Abstract [en]

    There is a great need for biomarkers in epilepsy, particularly markers of epileptogenesis. A first seizure will lead to epilepsy in 20–45 % of cases, but biomarkers that can identify these individuals are missing. The purpose of this study was to identify potential biomarkers of epilepsy/epileptogenesis in a cohort of adults with new-onset seizures, using quantitative proteomic analysis.

    Plasma was collected from 55 adults with new-onset seizures and sufficient follow-up to identify epilepsy. After a follow up period of two years, 63.6 % of the cohort had a diagnosis of epilepsy, whereas 36.4 % of patients only had a single seizure. Plasma proteins were extracted and labelled with tandem mass tags, then analyzed using mass spectrometry approach. Proteins that were up- or downregulated by ≥20 % and with a p-value of <0.05 were considered as differentially expressed and were also annotated to their processes and pathways.

    Several proteins were differentially expressed in the epilepsy group compared to controls. A total of 1075 proteins were detected, out of which 41 proteins were found to be significantly dysregulated in epilepsy patients. Many of these have been identified in experimental studies of epilepogenesis.

    We report plasma proteome profiling in new-onset epilepsy in a pilot study with 55 individuals. The identified proteins could be involved in pathways associated with epileptogenesis. The results should be seen as hypothesis-generating and targeted, confirmatory studies are needed.

  • 6.
    Cunningham, Janet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Rönnberg, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala Univ Hosp, Lab Clin Microbiol, Uppsala, Sweden..
    Castro Dopico, Xaquin
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
    Kolstad, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Albinsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala Univ Hosp, Lab Clin Microbiol, Uppsala, Sweden..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Nääs, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Klang, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Westman, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Zetterberg, Henrik
    Univ Gothenburg, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Sahlgrenska Acad, Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Mölndal, Sweden.;UCL Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England.;UCL, UK Dementia Res Inst, London, England..
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lundkvist, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Karlsson Hedestam, Gunilla B
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms2022In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 225, no 6, p. 965-970Article in journal (Refereed)
    Abstract [en]

    Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.

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  • 7.
    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.

  • 8.
    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)
  • 9.
    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.

  • 10. 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.

  • 11.
    Fahlström, Markus
    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.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engström, Mathias
    GE Healthcare, Applied Science Laboratory.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    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.
    Evaluation of Arterial Spin Labeling MRI: Comparison with 15O-Water PET on an Integrated PET/MR Scanner2021In: Diagnostics (Basel), ISSN 2075-4418, Vol. 11, no 5, article id 821Article in journal (Refereed)
    Abstract [en]

    Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.

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  • 12.
    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

  • 13.
    Ferlisi, Monica
    et al.
    Univ Hosp Verona, Unit Neurol A, Verona, Italy.
    Hocker, Sara
    Mayo Clin, Dept Neurol, Rochester, MN USA.
    Trinka, Eugen
    Paracelsus Med Univ, Salzburg, Austria.
    Shorvon, Simon
    UCL, Inst Neurol, Natl Hosp Neurol & Neurosurg, London, England.
    Etiologies and characteristics of refractory status epilepticus cases in different areas of the world: Results from a global audit2018In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 59 Suppl 2, p. 100-107Article in journal (Refereed)
    Abstract [en]

    To describe the demographics, etiologies, types of status epilepticus (SE), and outcomes in people with refractory and super-refractory SE from around the world, we prospectively collected cases of refractory SE (RSE) treated with continuous intravenous anesthetic drugs in an intensive care unit setting through online questionnaires using "active surveillance." We collected information about 776 cases of RSE in 50 countries over 4 years. Control of SE was achieved in 74% of the cases. Neurologic outcomes were poor in 41% of patients, and 24% died. Good outcome was associated with younger age and a history of epilepsy. Etiology strongly influenced the outcome. Patients from Asia were younger, more frequently presented with convulsive SE, and were more frequently affected by infectious etiologies when compared with patients from Europe and the Americas. Despite these differences, outcomes were similar in all countries. Demographics of patients with RSE in a global audit are similar to those in prior single center series, providing evidence of generalizability of those studies. Important differences exist among patients with RSE from different regions of the world, but these do not seem to significantly influence patient outcomes.

  • 14.
    Finnsson, Johannes
    et al.
    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.
    Savitcheva, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Melberg, Atle
    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.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy.2019In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, no 2, p. 135-142Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: LMNB1-related autosomal dominant leukodystrophy is caused by an overexpression of the protein lamin B1, usually due to a duplication of the LMNB1 gene. Symptoms start in 5th to 6th decade. This slowly progressive disease terminates with death. We studied brain glucose metabolism in this disease using 18 F-fluorodeoxyglucose positron emission tomography (PET).

    METHODS: We examined 8 patients, aged 48-64 years, in varying stages of clinical symptomatology. Two patients were investigated with quantitative PET on clinical indications after which six more patients were recruited. Absolute glucose metabolism was analyzed with the PVElab software in 6 patients and 18 healthy controls. A semiquantitative analysis using the CortexID software was performed in seven investigations, relating local metabolism levels to global glucose metabolism.

    RESULTS: The clinical quantitative PET revealed low global glucose metabolism, with the most marked reduction in the cerebellum. In the PVElab analysis, patients presented low mean glucose metabolism in the cerebellum, brainstem and global grey matter. In the semiquantitative analysis, 2 patients showed a decreased metabolism in the cerebellum and 4 patients a relatively higher metabolism in parts of the temporal lobes. Since none of the patients showed an increased metabolism in the quantitative analysis, we interpret these increases as "pseudo-increases" related to a globally reduced metabolism.

    CONCLUSIONS: Global reduction of grey matter glucose metabolism in this white matter disease most likely depends on a combination of cortical afferent dysfunction and, in later stages, neuronal loss. The lowest metabolism in the cerebellum is consistent with histopathological findings and prominent cerebellar symptoms.

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  • 15.
    Frithiof, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery. Karolinska institutet.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ashton, Nicholas
    Blennow, Kaj
    Zetterberg, Henrik
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rostedt Punga: Clinical Neurophysiology.
    Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study2021In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 132, no 7, p. 1733-1740Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim was to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in coronavirus disease 2019 (COVID-19) patients with intensive care unit acquired weakness (ICUAW).

    METHODS: An observational ICU cohort study including adult patients admitted to the ICU at Uppsala University Hospital, Uppsala, Sweden, from March 13th to June 8th 2020. We compared the clinical, electrophysiological and plasma biomarker data between COVID-19 patients who developed CIN/CIM and those who did not. Electrophysiological characteristics were also compared between COVID-19 and non-COVID-19 ICU patients.

    RESULTS: 111 COVID-19 patients were included, 11 of whom developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%) compared with a non-COVID-19 cohort (0%, p = 0.008). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group compared with those that did not develop CIN/CIM (both p = 0.001) and correlated with nerve amplitudes.

    CONCLUSIONS: CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness.

    SIGNIFICANCE: COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care, suggesting their potential as predictive biomarkers for CIN/CIM.

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  • 16.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurovetenskap.
    Ashton, Nicholas J.
    Jackmann, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurovetenskap.
    Pavel, Radu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Blennow, Kaj
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Lipcsey, Miklos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Westman, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Zetterberg, Henrik
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurovetenskap.
    The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in intensive care2022In: Journal of neuroradiology, ISSN 0150-9861, E-ISSN 1773-0406, Vol. 49, no 6, p. 421-427Article in journal (Refereed)
    Abstract [en]

    Background and purpose

    A wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood.

    Material and methods

    Patients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology.

    Results and conclusions

    The score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80.

    Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers.

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  • 17.
    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.

  • 18.
    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)
  • 19.
    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. 

  • 20.
    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, 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.

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  • 21.
    Jetté, Nathalie
    et al.
    Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY USA..
    Kirkpatrick, Martin
    Univ Dundee, Dept Child Hlth, Dundee, Scotland..
    Lin, Katia
    Univ Fed Santa Catarina, Div Neurol, Florianopolis, SC, Brazil..
    Fernando, Sanjaya M. S.
    Natl Epilepsy Ctr Colombo, Div Pediat Neurol, Colombo, Sri Lanka.;Natl Epilepsy Ctr Colombo, Colombo North Teaching Hosp, Colombo, Sri Lanka..
    French, Jacqueline A.
    New York Univ, NYU Grossman Sch Med, Dept Neurol, New York, NY USA..
    Jehi, Lara
    Cleveland Clin Epilepsy Ctr, Cleveland, OH USA..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurovetenskap.
    Triki, Chahnez C.
    Univ Sfax, Hedi Chaker Hosp, Dept Child Neurol, Sfax, Tunisia..
    Wiebe, Samuel
    Univ Cape Town, Neurosci Inst, Red Cross War Mem Childrens Hosp, Dept Paediat Neurol, Cape Town, South Africa..
    Wimshurst, Jo
    Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada..
    Brigo, Francesco
    Hosp Merano, Dept Neurol, Merano, Italy..
    What is a clinical practice guideline?: A roadmap to their development. Special report from the Guidelines Task Force of the International League Against Epilepsy2022In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 63, no 8, p. 1920-1929Article in journal (Refereed)
    Abstract [en]

    Clinical practice guidelines (CPGs) are statements that provide evidence-based recommendations aimed at optimizing patient care. However, many other documents are often published as "guidelines" when they are not; these documents, although also important in clinical practice, are usually not systematically produced following rigorous processes linking the evidence to the recommendations. Specifically, the International League Against Epilepsy (ILAE) guideline development toolkit aims to ensure that high-quality CPGs are developed to fill knowledge gaps and optimize the management of epilepsy. In addition to adhering to key methodological processes, guideline developers need to consider that effective CPGs should lead to improvements in clinical processes of care and health care outcomes. This requires monitoring the effectiveness of epilepsy-related CPGs and interventions to remove the barriers to epilepsy CPG implementation. This article provides an overview of what distinguishes quality CPGs from other documents and discusses their benefits and limitations. We summarize the recently revised ILAE CPG development process and elaborate on the barriers and facilitators to guideline dissemination, implementation, and adaptation.

  • 22.
    Juran, Stephanie A.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Div Psychol, Stockholm, Sweden;Karolinska Inst, Inst Environm Med, Unit Work Environm Toxicol, Stockholm, Sweden.
    Lundstrom, Johan N.
    Karolinska Inst, Dept Clin Neurosci, Div Psychol, Stockholm, Sweden;Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA;Univ Penn, Dept Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA.
    Geigant, Michael
    Stockholm Cty Council, Mental Hlth Care, Stockholm, Sweden.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Div Psychol, Stockholm, Sweden.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Div Psychol, Stockholm, Sweden.
    Olsson, Mats J.
    Karolinska Inst, Dept Clin Neurosci, Div Psychol, Stockholm, Sweden.
    Unilateral Resection of the Anterior Medial Temporal Lobe Impairs Odor Identification and Valence Perception2016In: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 6, article id 2015Article in journal (Refereed)
    Abstract [en]

    The anterior medial temporal lobe (TL), including the amygdala, has been implicated in olfactory processing, e.g., coding for intensity and valence, and seems also involved in memory. With this background, the present study evaluated whether anterior medial TL-resections in TL epilepsy affected intensity and valence ratings, as well as free and cued identification of odors. These aspects of odor perception were assessed in 31 patients with unilateral anterior medial TL-resections (17 left, 14 right) and 16 healthy controls. Results suggest that the anterior medial TL is in particular necessary for free, but also cued, odor identification. TL resection was also found to impair odor valence, but not intensity ratings. Left resected patients rated nominally pleasant and unpleasant odors as more neutral suggesting a special role for the left anterior TL in coding for emotional saliency in response to odors.

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  • 23.
    Knight, Ann
    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 rituximab2017In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56, no 5, p. 855-856Article in journal (Refereed)
  • 24. 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)
  • 25.
    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.))
  • 26.
    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)
  • 27. Larsson, David
    et al.
    Baftiu, Arton
    Johannessen Landmark, Cecilie
    von Euler, Mia
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Landtblom: Neurology.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Landtblom: Neurology.
    Zelano, Johan
    Association Between Antiseizure Drug Monotherapy and Mortality for Patients With Poststroke Epilepsy2022In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 79, no 2, p. 169-175Article in journal (Refereed)
    Abstract [en]

    Importance: There is little evidence to guide the choice of antiseizure medication (ASM) for patients with poststroke epilepsy. Theoretical concerns about detrimental effects of ASMs on survival exist. Enzyme-inducing drugs could interfere with secondary stroke prevention. The US Food and Drug Administration recently issued a safety announcement about the potential proarrhythmic properties of lamotrigine.

    Objective: To investigate whether mortality varies with specific ASMs among patients with poststroke epilepsy.

    Design, Setting, and Participants: A cohort study was conducted using individual-level data from linked registers on all adults in Sweden with acute stroke from July 1, 2005, to December 31, 2010, and subsequent onset of epilepsy before December 31, 2014. A total of 2577 patients receiving continuous ASM monotherapy were eligible for the study. Data were analyzed between May 27, 2019, and April 8, 2021.

    Exposures: The dispensed ASM (Anatomical Therapeutic Chemical code N03A) determined exposure status, and the first dispensation date marked the start of treatment.

    Main Outcomes and Measures: The primary outcome, all-cause death, was analyzed using Cox proportional hazards regression with carbamazepine as the reference. Cardiovascular death (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I0-I99 as the underlying cause) was assessed using Fine-Gray competing risk regression models.

    Results: A total of 2577 patients (1400 men [54%]; median age, 78 years [IQR, 69-85 years]) were included. The adjusted hazard ratio of all-cause death compared with carbamazepine was 0.72 (95% CI, 0.60-0.86) for lamotrigine, 0.96 (95% CI, 0.80-1.15) for levetiracetam, 1.40 (95% CI, 1.23-1.59) for valproic acid, 1.16 (95% CI, 0.88-1.51) for phenytoin, and 1.16 (95% CI, 0.81-1.66) for oxcarbazepine. The adjusted hazard ratio of cardiovascular death compared with carbamazepine was 0.76 (95% CI, 0.61-0.95) for lamotrigine, 0.77 (95% CI, 0.60-0.99) for levetiracetam, 1.40 (95% CI, 1.19-1.64) for valproic acid, 1.02 (95% CI, 0.71-1.47) for phenytoin, and 0.71 (95% CI, 0.42-1.18) for oxcarbazepine.

    Conclusions and Relevance: This cohort study's findings suggest differences in survival between patients treated with different ASMs for poststroke epilepsy. Patients receiving lamotrigine monotherapy had significantly lower mortality compared with those receiving carbamazepine. The opposite applied to patients prescribed valproic acid, who had a higher risk of cardiovascular and all-cause death. Levetiracetam was associated with a reduced risk of cardiovascular death compared with carbamazepine, but there was no significant difference in overall mortality.

  • 28.
    Larsson, David
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden; Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Kumlien, Eva
    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.
    Retention rate of first antiepileptic drug in poststroke epilepsy: A nationwide study2019In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 64, p. 29-33Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe the retention rates of first antiepileptic drugs (AEDs) in patients with poststroke epilepsy on a nationwide scale.

    Methods: The Swedish Stroke Register, which has 94% coverage and high-resolution data on stroke, comorbidities, and disability, was cross-referenced to the National Patient Register, Drug Register, and Cause-of-Death Register. Patients with onset of AED-treated epilepsy after stroke in 2005–2010 were included. An algorithm based on prescription renewal intervals was used to analyze treatment data until the end of 2014.

    Results: A total of 4991 patients were included. First AEDs analyzed were carbamazepine (n = 2373), valproic acid (n = 943), levetiracetam (n = 555), lamotrigine (n = 519), phenytoin (n = 176), and oxcarbazepine (n = 89). The five-year retention rate was highest for lamotrigine (75%, 95%CI:70.4–79.4), followed by levetiracetam (69%, 95%CI:62.9–74.3), oxcarbazepine (68%, 95%CI:55.2–79.8), valproic acid (62%, 95%CI:57.8–66.4), carbamazepine (60%, 95%CI:57.6–62.4), and phenytoin (55%, 95%CI:45.2–64.0). There were minor differences in baseline characteristics with low levels of disability being slightly more common in patients treated with lamotrigine and levetiracetam. Atrial fibrillation and hypertension were more common in patients treated with levetiracetam, and atrial fibrillation was less common in patients treated with carbamazepine. In a Cox model adjusted for baseline characteristics, the risk of discontinuation was lower for lamotrigine (HR 0.53, 95%CI:0.43-0.67) and levetiracetam (HR 0.75, 95%CI:0.60-0.94) when compared to carbamazepine.

    Conclusions: Lamotrigine and levetiracetam have higher retention rates than carbamazepine in poststroke epilepsy. This is in agreement with existing small RCTs in this patient group.

  • 29.
    Lindqvist, Isa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Cunningham, Janet L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Mulder, Jan
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Feresiadou, Amalia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Myoclonus in patients with COVID-19: Findings of autoantibodies against brain structures in cerebrospinal fluid2023In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 30, no 10, p. 3142-3148Article in journal (Refereed)
    Abstract [en]

    Background and purpose

    COVID-19 is associated with multiple neurological manifestations. The clinical presentation, trajectory, and treatment response for three cases of myoclonus during COVID-19 infection, with no previous neurological disease, are decsribed.

    Metods

    Analysis of cerebrospinal fluid from the cases using indirect immunohistochemistry.

    Results

    Antibodies against rodent brain tissue, and similarities in staining patterns were observed, indicating the presence of antineuronal immunoglobulin G autoantibodies targeting astrocytes in the hippocampus.

    Conclusion

    Our results demontrate cerebrospinal fluid antineuronal antibodies indicating an an autoimmune involvment in the pathogenesis in COVID-19 associated myoclonus.

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  • 30.
    Lindskog, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Méar, Loren
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Fällmar, David
    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 Medical Sciences, Neurology.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Casar Borota, Olivera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Department of Clinical Pathology and Cytology, Uppsala University Hospital, 751 85 Uppsala, Sweden.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Protein Expression Profile of ACE2 in the Normal and COVID-19-Affected Human Brain.2022In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 21, no 9, p. 2137-2145Article in journal (Refereed)
    Abstract [en]

    SARS-coronavirus 2 (SARS-CoV-2) that caused the coronavirus disease 2019 (COVID-19) pandemic has posed to be a global challenge. An increasing number of neurological symptoms have been linked to the COVID-19 disease, but the underlying mechanisms of such symptoms and which patients could be at risk are not yet established. The suggested key receptor for host cell entry is angiotensin I converting enzyme 2 (ACE2). Previous studies on limited tissue material have shown no or low protein expression of ACE2 in the normal brain. Here, we used stringently validated antibodies and immunohistochemistry to examine the protein expression of ACE2 in all major regions of the normal brain. The expression pattern was compared with the COVID-19-affected brain of patients with a varying degree of neurological symptoms. In the normal brain, the expression was restricted to the choroid plexus and ependymal cells with no expression in any other brain cell types. Interestingly, in the COVID-19-affected brain, an upregulation of ACE2 was observed in endothelial cells of certain patients, most prominently in the white matter and with the highest expression observed in the patient with the most severe neurological symptoms. The data shows differential expression of ACE2 in the diseased brain and highlights the need to further study the role of endothelial cells in COVID-19 disease in relation to neurological symptoms.

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    fulltext
  • 31.
    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

  • 32.
    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)
  • 33.
    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)
  • 34.
    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)
  • 35.
    Mulder, Jan
    et al.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Feresiadou, Amalia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Rasmusson, Annica J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Autoimmune Encephalitis Presenting With Malignant Catatonia in a 40-Year-Old Male Patient With COVID-192021In: American Journal of Psychiatry, ISSN 0002-953X, E-ISSN 1535-7228, Vol. 178, no 6, p. 485-489Article in journal (Other academic)
    Abstract [en]

    A 40-year-old man who had previously had symptoms of and a positive test for COVID-19, but had no other previous medical or psychiatric conditions or medication, presented to the emergency unit with acute debut of agitation, grimacing, and repetitive speech and movements (verbigeration and stereotypies); his behavior was bizarre, disorganized, hyperkinetic, and uncooperative and met DSM-5 criteria for catatonia. Twenty-two days before admission, the patient had developed COVID-19-related respiratory symptoms and fatigue, which did not require hospital care. He had tested positive for SARS-CoV-2 RNA in a naso-pharyngeal swab using the Abbott RealTime SARSCoV-2 assay on the Abbott m2000 platform (day 14; Figure 1A). Anosmia and ageusia were not present. During the several days before admission, he had suffered from a headache. On admission (day 22), he no longer had respiratory symptoms but he did have a fever (38.4 degrees C). He made no eye contact, his reflexes were normal, and Babinski's sign was absent. Treatment with antibiotics and acyclovir was initiated until the tests excluded bacterial infection and herpes encephalitis. Brain CT, MRI, and blood tests were unremarkable. The patient was lightly sedated with midazolam, followed with dexmedetomidine. Neuroleptics were not used. Lumbar puncture showed a high red blood cell count (19,000 cellsx10(6)/L) secondary to traumatic lumbar puncture. CSF cell count indicated pleocytosis, with 23x10(6)/L mononuclear and 8x10(6)/L polymorphonuclear cells. Signs of blood-brain barrier disruption were present, with elevated albumin levels in CSF, at 838 mg/L (reference, <400 mg/L), and the CSF/serum albumin quotient was 15.6 (reference, <6.8). Interleukin-6 (IL-6) in CSF was elevated at 102.1 pg/mL ( reference, <5 pg/mL), but CSF levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and tau protein were normal. PCR tests for SARS- CoV-2 were repeatedly negative in CSF and nasopharyngeal swabs. Antineuronal antibodies against N-methyl-D-aspartate receptor (NMDAR), glutamic acid decarboxylase, contactin-associated protein-like 2, leucine-rich, glioma inactivated 1, and ganglioside antibodies in serum and CSF were negative (Euroimmune, Lubeck, Germany). Hours later, the patient's state deteriorated, and his temperature rose to 39 degrees C. He became mutistic and showed signs of autonomic instability, with recurrent episodes of fluctuating heart rate and arterial blood pressure and periods of oxygen desaturation (Figure 1B). The hypertension was difficult to treat, despite high doses of clonidine and labetalol. Plasma lactate levels varied between 0.6 and 8 mmol/L (reference, 0.8-2.0 mmol/L), but myoglobulin and creatine kinase myocardial band (CKMB) remained normal. The patient's pupil size, reaction to light, and oculocephalic reflex were normal. Slow, horizontal roving eye movements were noted. The patient displayed decorticate posturing and increased tonus; he resisted movement of arms and jaw but had normal tonus in the legs. Hyperreflexia was present, with bilateral foot clonus and Babinski's sign but no neck stiffness. Anesthesia was induced with propofol and clonidine to facilitate endotracheal intubation. D-Dimer was slightly elevated (1.2 mg/L; reference <0.5 mg/L), without signs of thromboembolic events. Respiration and cardiovascular function remained stable. Continuous EEG monitoring showed nonspecific slowing with left hemisphere predominance without epileptiformactivity. An episode of asystole with spontaneous recovery, episodes of bradycardia of 27 bpm and repeated P waves without QRS complexes were interpreted as third-degree atrioventricular block. Signs of autoimmune encephalitis were present, but this case did not meet the proposed criteria (1, 2). Standard radiological findings were normal, and the discrete pleocytosis and elevated protein in CSF was nonspecific. Although the diagnosis remained uncertain, parainfectious autoimmune encephalitis was still suspected. Plasmapheresis was initiated and repeated three times over 4 days. After two courses, the patient was extubated and was autonomically stable. Eye movement was normalized and hyperreflexia was less prominent, but bilateral Babinski's sign persisted. Treatment was initiated with 1 g methylprednisolone per day. On day 28, the patient showed a dramatic improvement. He was awake, oriented, and communicative but had no memories from the past several days. He was distracted by complex visual hallucinations of black and white figures (animals and famous people) appearing on his right side. He described them as being in a mirror (suspected polyopia). These figures were often stationary but could make gestures. He also described an experience of feeling that the world was different-strange and unreal, with brighter colors (suspected hyperchromatopsia and derealization). He had frequent episodes of failing to recognize his right hand and leg as his own and experienced their movement as unexpected (alien hand syndrome). He denied the presence of other perceptual disturbances. His understanding of Swedish, his second language, seemed intact, but his responses were mostly monosyllabic. He could name his children and give his personal identification number but was slow and made mistakes in naming the months. Mild visual object agnosia was present. Simultanagnosia was prominent, he showed deficits in isolating figures in a tangled pictorial array, and he could depict details but excluded the global features of complex pictures. He could recall one of three objects after a short delay and draw a correct clock but required three repetitions of the instructions. He had difficulty mirroring and performing fine movements. Finally, he showed no signs of visual neglect and could read text. The patient's EEG was normal. A second lumbar puncture showed pleocytosis, 10 mononuclear cells and 1 polymorphonuclear cell x10(6)/L, elevated IgG levels and IgG index, and two oligoclonal bands in CSF not represented in serum, indicating intrathecal production of antibodies. The IL-6 level in CSF was normalized. GFAP and tau remained normal, but NfL was increased to 1,030 ng/L (reference, <890 ng/L). A second MRI and a standard neurological examination on day 31 were normal. The hallucinations were less frequent. The patient described increased emotional lability and mental fatigue, with disturbed short-term memory and decision making. He also found it challenging to recognize the voices and faces of acquaintances. Serology on day 33 was strongly positive (index 8.88 S/CO [signal/cutoff]) for IgG against SARS- CoV-2 analyzed with the CE-labeled SARS- CoV-2 IgG kit with nucleoprotein-based antigen with the Abbott Architect i2000SR Analyzer at the Laboratory of Clinical Microbiology, Uppsala University Hospital, as previously described (3). [F-18]fluorodeoxyglucose ([F-18]FDG) PET scan on day 35 (after treatment) showed high bilateral uptake in the striatum (caudate nucleus and putamen) compared with the cortex (Figure 1C). Using immunohistochemistry in the research lab, we detected IgG autoantibodies against mouse brain neuronal proteins in serum and CSF collected at admission (Figure 2). Neuronal labeling intensity was strongest in the CA3 in the hippocampal formation, layer V in the somatosensory cortex, and the paraventricular and reticular nucleus in the thalamus. A subset of ependymal cells located in the ventricle wall and choroid plexus revealed strong immunoreactivity of the (peri)nuclear compartment and cytoplasm. Immunoreactivity of neuropil was most intense in the caudate putamen, revealing neuronal processes and spine-like structures. Posttreatment IgG immunoreactivity in the (peri)nuclear compartment and neuropil was notably reduced, reaching the levels of reference CSF and serum.

  • 36.
    Mulder, Jan
    et al.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Lindqvist, Isa
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Rasmusson, Annica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Husen, Evelina
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Cunningham, Janet L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Indirect immunofluorescence for detecting anti-neuronal autoimmunity in CSF after COVID-19-Possibilities and pitfalls2021In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 94, p. 473-474Article in journal (Other academic)
  • 37.
    Peltola, Jukka
    et al.
    Tampere Univ, Dept Neurol, Tampere, Finland.;Tampere Univ Hosp, Tampere, Finland..
    Colon, Albert A.
    Acad Ctr Epileptol Kempenhaeghe MUMC, Maastricht, Netherlands..
    Pimentel, Jose
    Ctr Hosp Univ Lisboa Norte, Hosp Santa Maria, Dept Neurosci & Mental Hlth, Lisbon, Portugal..
    Coenen, Volker
    Univ Klinikum Freiburg, Dept Stereotact & Funct Neurosurg, Freiburg, Germany..
    Gil-Nagel, Antonio
    Hosp Ruber Int, Neurol Dept, Epilepsy Program, Madrid, Spain..
    Goncalves Ferreira, Antonio
    Ctr Hosp Lisboa Norte, Hosp Santa Maria, Dept Neurosurg, Lisbon, Portugal..
    Lehtimaki, Kai S.
    Tampere Univ Hosp, Tampere, Finland.;Tampere Univ Hosp, Dept Neurosurg, Tampere, Finland..
    Ryvlin, Philippe
    Ctr Hosp Univ Vaudois CHUV, Dept Neurosci Clin, Lausanne, Switzerland..
    Taylor, Rod
    Univ Glasgow, Inst Hlth & Well Being, MRC CSO Social & Publ Hlth Sci Unit, Glasgow, Scotland.;Univ Glasgow, Inst Hlth & Well Being, Robertson Ctr Biostat, Glasgow, Scotland.;Univ Exeter, Coll Med & Hlth, Exeter, England..
    Ackermans, Linda
    Acad Ctr Epileptol Kempenhaeghe MUMC, Maastricht, Netherlands.;Maastricht Univ, Med Ctr, Dept Neurosurg, Maastricht, Netherlands..
    Ardesch, Jacqueline
    Stichting Epilepsie Instellingen Nederland SEIN, Zwolle, Netherlands..
    Bentes, Carla G.
    Ctr Hosp Univ Lisboa Norte, Hosp Santa Maria, Dept Neurosci & Mental Hlth, Neurophysiol Monitoring Unit, Lisbon, Portugal.;Univ Lisbon, Fac Med, Lisbon, Portugal..
    Bosak, Magdalena
    Jagiellonian Univ Med Coll, Fac Med, Dept Neurol, Krakow, Poland..
    Burneo, Jorge E.
    Western Univ, London, ON, Canada..
    Chamadoira, Clara
    Ctr Hosp Univ Sao Joao, Neurosurg Dept, Porto, Portugal..
    Elger, Christian
    Univ Hosp Bonn, Dept Epileptol, Bonn, Germany..
    Eross, Lorand
    Natl Inst Clin Neurosci, Budapest, Hungary..
    Fabo, Daniel
    Natl Inst Neurosci, Budapest, Hungary..
    Faulkner, Howard
    North Bristol NHS Trust, Bristol, England..
    Gawlowicz, Jacek
    Wojewodzki Szpital Specjalist Lublinie, Lublin, Poland..
    Gharabaghi, Alireza
    Univ Tubingen, Inst Neuromodulat & Neurotechnol, Dept Neurosurg & Neurotechnol, Tubingen, Germany..
    Iacoangeli, Maurizio
    Univ Politecn Marche, Umberto I Gen Univ Hosp, Dept Neurosurg, Ancona, Italy..
    Janszky, Jozsef
    Univ Pecs, Med Sch, Dept Neurol, Pecs, Hungary..
    Jarvenpaa, Soila H.
    Tampere Univ, Dept Neurol, Tampere, Finland.;Tampere Univ Hosp, Tampere, Finland..
    Kaufmann, Elisabeth
    Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany..
    Kho, Kuan H.
    Med Spectrum Twente MST, Enschede, Netherlands..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology. Uppsala Univ, Dept Neurosci, Uppsala, Sweden..
    Laufs, Helmut
    Christian Albrechts Univ Kiel, Klin Neurol, Univ Klinikum Schleswig Holstein, Campus Kiel, Kiel, Germany..
    Lettieri, Christian
    S Maria della Misericordia Univ Hosp, Dept Neurosci, Neurol & Clin Neurophysiol Unit, Udine, Italy..
    Linhares, Paulo
    Ctr Hosp Univ Sao Joao, Neurosurg Dept, Porto, Portugal..
    Noachtar, Soheyl
    Klinikum Univ Munchen, Grosshadern Neurol Klin & Poliklin, Munich, Germany..
    Parrent, Andrew K.
    Western Univ, London, ON, Canada..
    Pataraia, Ekaterina
    Med Univ Wien, Vienna, Austria..
    Patel, Nikunj K.
    North Bristol NHS Trust, Southmead Hosp, Bristol, England..
    Peralta, Ana Rita
    Univ Lisbon, Fac Med, Lisbon, Portugal.;Ctr Hosp Univ Lisboa Norte, Hosp Santa Maria, Dept Neurol, Dept Neurosci & Mental Hlth,Lab EEG Sleep, Lisbon, Portugal..
    Racz, Attila
    Univ Hosp Bonn, Dept Epileptol, Bonn, Germany..
    Campos, Alexandre Rainha A.
    Ctr Hosp Lisboa Norte, Hosp Santa Maria, Dept Neurosurg, Lisbon, Portugal..
    Rego, Ricardo
    Ctr Hosp Univ Sao Joao, Neurol Dept, Neurophysiol Unit, Porto, Portugal..
    Ricciuti, Riccardo
    Viterbo Hosp, Dept Neurosurg, Viterbo, Italy..
    Rona, Sabine
    Univ Tubingen, Dept Neurosurg & Neurotechnol, Epilepsy Unit, Tubingen, Germany..
    Rouhl, Rob P. W.
    Acad Ctr Epileptol Kempenhaeghe MUMC, Maastricht, Netherlands.;Maastricht Univ, Med Ctr, Dept Neurol, Maastricht, Netherlands.;Maastricht Univ, Sch Mental Hlth & Neurosci, Maastricht, Netherlands..
    Schulze-Bonhage, Andreas
    Univ Hosp Freiburg, Freiburg, Germany..
    Schuurman, Rick
    Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Sprengers, Mathieu
    Univ Ghent, Ghent Univ Hosp, Dept Neurol, Ghent, Belgium..
    Sufianov, Albert
    IM Sechenov First Moscow State Med Univ, Fed Ctr Neurosurg Tyumen, Moscow, Russia..
    Temel, Yasin
    Maastricht Univ, Med Ctr, Dept Neurosurg, Maastricht, Netherlands..
    Theys, Tom
    UZ Leuven, Leuven, Belgium..
    Van Paesschen, Wim
    UZ Leuven, Dept Neurol, Leuven, Belgium.;Katholieke Univ Leuven, Lab Epilepsy Res, Leuven, Belgium..
    Van Roost, Dirk
    Univ Ghent, Ghent Univ Hosp, Dept Neurosurg, Ghent, Belgium..
    Vaz, Rui
    Ctr Hosp Univ Sao Joao, Neurosurg Dept, Porto, Portugal..
    Vonck, Kristl
    Univ Ghent, Ghent Univ Hosp, Dept Neurol, Ghent, Belgium..
    Wagner, Louis
    Acad Ctr Epileptol Kempenhaeghe MUMC, Maastricht, Netherlands..
    Zwemmer, Jack C.
    Stichting Epilepsie Instellingen Nederland SEIN, Heemstede, Netherlands..
    Abouihia, Abdallah
    Medtron Internal Trading Sarl, Clin Dept, Tolochenaz, Switzerland..
    Brionne, Thomas
    Medtron Internal Trading Sarl, Clin Dept, Tolochenaz, Switzerland..
    Gielen, Frans
    Medtron Bakken Res Ctr, Maastricht, Netherlands..
    Boon, Paul A. J. M.
    Univ Ghent, Ghent Univ Hosp, Dept Neurol, Ghent, Belgium..
    Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry2023In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 100, no 18, p. E1852-E1865Article in journal (Refereed)
    Abstract [en]

    Background and ObjectivesThe efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice.MethodsMORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes.ResultsOf the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported.DiscussionThe MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation.Classification of EvidenceThis study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy.

  • 38.
    Peltola, Jukka
    et al.
    Tampere Univ, Dept Neurol, Tampere, Finland.;Tampere Univ Hosp, Tampere, Finland..
    Colon, Albert A.
    Acad Ctr Epileptol Kempenhaeghe MUMC, Maastricht, Netherlands..
    Pimentel, Jose
    Ctr Hosp Univ Lisboa Norte, Hosp Santa Maria, Dept Neurosci & Mental Hlth, Lisbon, Portugal..
    Coenen, Volker
    Univ Klinikum Freiburg, Dept Stereotact & Funct Neurosurg, Freiburg, Germany..
    Gil-Nagel, Antonio
    Hosp Ruber Int, Neurol Dept, Epilepsy Program, Madrid, Spain..
    Goncalves Ferreira, Antonio
    Ctr Hosp Lisboa Norte, Hosp Santa Maria, Dept Neurosurg, Lisbon, Portugal..
    Lehtimaki, Kai S.
    Tampere Univ Hosp, Tampere, Finland.;Tampere Univ Hosp, Dept Neurosurg, Tampere, Finland..
    Ryvlin, Philippe
    Ctr Hosp Univ Vaudois CHUV, Dept Neurosci Clin, Lausanne, Switzerland..
    Taylor, Rod
    Univ Glasgow, Inst Hlth & Well Being, MRC CSO Social & Publ Hlth Sci Unit, Glasgow, Scotland.;Univ Glasgow, Inst Hlth & Well Being, Robertson Ctr Biostat, Glasgow, Scotland.;Univ Exeter, Coll Med & Hlth, Exeter, England..
    Ackermans, Linda
    Acad Ctr Epileptol Kempenhaeghe MUMC, Maastricht, Netherlands.;Maastricht Univ, Med Ctr, Dept Neurosurg, Maastricht, Netherlands..
    Ardesch, Jacqueline
    Stichting Epilepsie Instellingen Nederland SEIN, Zwolle, Netherlands..
    Bentes, Carla G.
    Ctr Hosp Univ Lisboa Norte, Hosp Santa Maria, Dept Neurosci & Mental Hlth, Neurophysiol Monitoring Unit, Lisbon, Portugal.;Univ Lisbon, Fac Med, Lisbon, Portugal..
    Bosak, Magdalena
    Jagiellonian Univ Med Coll, Fac Med, Dept Neurol, Krakow, Poland..
    Burneo, Jorge E.
    Western Univ, London, ON, Canada..
    Chamadoira, Clara
    Ctr Hosp Univ Sao Joao, Neurosurg Dept, Porto, Portugal..
    Elger, Christian
    Univ Hosp Bonn, Dept Epileptol, Bonn, Germany..
    Eross, Lorand
    Natl Inst Clin Neurosci, Budapest, Hungary..
    Fabo, Daniel
    Natl Inst Neurosci, Budapest, Hungary..
    Faulkner, Howard
    North Bristol NHS Trust, Bristol, England..
    Gawlowicz, Jacek
    Wojewodzki Szpital Specjalist Lublinie, Lublin, Poland..
    Gharabaghi, Alireza
    Univ Tubingen, Inst Neuromodulat & Neurotechnol, Dept Neurosurg & Neurotechnol, Tubingen, Germany..
    Iacoangeli, Maurizio
    Univ Politecn Marche, Umberto I Gen Univ Hosp, Dept Neurosurg, Ancona, Italy..
    Janszky, Jozsef
    Univ Pecs, Med Sch, Dept Neurol, Pecs, Hungary..
    Jarvenpaa, Soila H.
    Tampere Univ, Dept Neurol, Tampere, Finland.;Tampere Univ Hosp, Tampere, Finland..
    Kaufmann, Elisabeth
    Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany..
    Kho, Kuan H.
    Med Spectrum Twente MST, Enschede, Netherlands..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Laufs, Helmut
    Christian Albrechts Univ Kiel, Klin Neurol, Univ Klinikum Schleswig Holstein, Campus Kiel, Kiel, Germany..
    Lettieri, Christian
    S Maria della Misericordia Univ Hosp, Dept Neurosci, Neurol & Clin Neurophysiol Unit, Udine, Italy..
    Linhares, Paulo
    Ctr Hosp Univ Sao Joao, Neurosurg Dept, Porto, Portugal..
    Noachtar, Soheyl
    Klinikum Univ Munchen, Grosshadern Neurol Klin & Poliklin, Munich, Germany..
    Parrent, Andrew K.
    Western Univ, London, ON, Canada..
    Pataraia, Ekaterina
    Med Univ Wien, Vienna, Austria..
    Patel, Nikunj K.
    North Bristol NHS Trust, Southmead Hosp, Bristol, England..
    Peralta, Ana Rita
    Univ Lisbon, Fac Med, Lisbon, Portugal.;Ctr Hosp Univ Lisboa Norte, Hosp Santa Maria, Dept Neurol, Dept Neurosci & Mental Hlth,Lab EEG Sleep, Lisbon, Portugal..
    Racz, Attila
    Univ Hosp Bonn, Dept Epileptol, Bonn, Germany..
    Campos, Alexandre Rainha A.
    Ctr Hosp Lisboa Norte, Hosp Santa Maria, Dept Neurosurg, Lisbon, Portugal..
    Rego, Ricardo
    Ctr Hosp Univ Sao Joao, Neurol Dept, Neurophysiol Unit, Porto, Portugal..
    Ricciuti, Riccardo
    Viterbo Hosp, Dept Neurosurg, Viterbo, Italy..
    Rona, Sabine
    Univ Tubingen, Dept Neurosurg & Neurotechnol, Epilepsy Unit, Tubingen, Germany..
    Rouhl, Rob P. W.
    Acad Ctr Epileptol Kempenhaeghe MUMC, Maastricht, Netherlands.;Maastricht Univ, Med Ctr, Dept Neurol, Maastricht, Netherlands.;Maastricht Univ, Sch Mental Hlth & Neurosci, Maastricht, Netherlands..
    Schulze-Bonhage, Andreas
    Univ Hosp Freiburg, Freiburg, Germany..
    Schuurman, Rick
    Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Sprengers, Mathieu
    Univ Ghent, Ghent Univ Hosp, Dept Neurol, Ghent, Belgium..
    Sufianov, Albert
    IM Sechenov First Moscow State Med Univ, Fed Ctr Neurosurg Tyumen, Moscow, Russia..
    Temel, Yasin
    Maastricht Univ, Med Ctr, Dept Neurosurg, Maastricht, Netherlands..
    Theys, Tom
    UZ Leuven, Leuven, Belgium..
    Van Paesschen, Wim
    UZ Leuven, Dept Neurol, Leuven, Belgium.;Katholieke Univ Leuven, Lab Epilepsy Res, Leuven, Belgium..
    Van Roost, Dirk
    Univ Ghent, Ghent Univ Hosp, Dept Neurosurg, Ghent, Belgium..
    Vaz, Rui
    Ctr Hosp Univ Sao Joao, Neurosurg Dept, Porto, Portugal..
    Vonck, Kristl
    Univ Ghent, Ghent Univ Hosp, Dept Neurol, Ghent, Belgium..
    Wagner, Louis
    Acad Ctr Epileptol Kempenhaeghe MUMC, Maastricht, Netherlands..
    Zwemmer, Jack C.
    Stichting Epilepsie Instellingen Nederland SEIN, Heemstede, Netherlands..
    Abouihia, Abdallah
    Medtron Internal Trading Sarl, Clin Dept, Tolochenaz, Switzerland..
    Brionne, Thomas
    Medtron Internal Trading Sarl, Clin Dept, Tolochenaz, Switzerland..
    Gielen, Frans
    Medtron Bakken Res Ctr, Maastricht, Netherlands..
    Boon, Paul A. J. M.
    Univ Ghent, Ghent Univ Hosp, Dept Neurol, Ghent, Belgium..
    Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry2023In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 100, no 18, p. E1852-E1865Article in journal (Refereed)
    Abstract [en]

    Background and Objectives The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice.

    Methods MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes.

    Results Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported.

    Discussion The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation.

    Classification of Evidence This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy.

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  • 39. 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.

  • 40. 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)
  • 41. 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.

  • 42.
    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)
  • 43.
    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.

  • 44.
    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)
  • 45.
    Svedung-Wettervik, Teodor
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    von Seth, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Velickaite, Vilma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Intracranial Pressure Dynamics and Cerebral Vasomotor Reactivity in Coronavirus Disease 2019 Patient With Acute Encephalitis2020In: Critical care explorations, ISSN 2639-8028, Vol. 2, no 8, article id e0197Article in journal (Refereed)
    Abstract [en]

    Objectives: We describe the intracranial pressure dynamics andcerebral vasomotor reactivity in a coronavirus disease 2019 patient with acute encephalitis treated with cerebrospinal fluid drainage and therapeutic plasma exchange.

    Data Sources: Coronavirus disease ICU, Uppsala University Hospital,Sweden.

    Study Selection: Case report.

    Data Extraction: Radiology, intracranial pressure, intracranial compliance (correlation between intracranial pressure amplitude and mean intracranial pressure), cerebral vasomotor reactivity (pressure reactivity index), arterial blood pressure, cerebrospinal fluid chemistry, and treatment.

    Data Synthesis: None.

    Conclusions: This is the first reported case of intracranial pressure monitoring in a patient with acute encephalitis following corona virus disease 2019. Intracranial pressure data exhibited a high incidence of plateau waves with intracranial pressure insults above 40 mm Hg that required cerebrospinal fluid drainage. Intracranial compliance was low, and pressure reactivity was intact. It is probable that the combination of low intracranial compliance and intact pressure autoregulation explain the high degree of plateau intracranial pressure waves and intracranial pressure variability.

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  • 46.
    Tomson, Torbjorn
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neurol, SE-17176 Stockholm, Sweden..
    Battino, Dina
    Carlo Besta Fdn, IRCCS Neurol Inst, Dept Neurophysiol & Expt Epileptol, Epilepsy Ctr, Milan, Italy..
    Bonizzoni, Erminio
    Univ Milan, Dept Clin Sci & Community, Sect Med Stat Biometry & Epidemiol, Fac Med & Surg, Milan, Italy..
    Craig, John
    Belfast Hlth & Social Care Trust, Dept Neurosci Acute & Unscheduled Care, Belfast, Antrim, North Ireland..
    Lindhout, Dick
    Univ Med Ctr Utrecht, Dept Genet, Utrecht, Netherlands.;SEIN, Heemstede, Netherlands..
    Perucca, Emilio
    Univ Pavia, Dept Internal Med & Therapeut, Pavia, Italy.;IRCCS Mondino Fdn, Clin Trial Ctr, Pavia, Italy..
    Sabers, Anne
    Univ State Hosp, Epilepsy Clin, Dept Neurol, Rigshosp Blegdamsvej, Copenhagen, Denmark..
    Thomas, Sanjeev V.
    Sree ChitraTirunal Inst Med Sci & Technol, Dept Neurol, Trivandrum, Kerala, India..
    Vajda, Frank
    Univ Melbourne, Royal Melbourne Hosp, Dept Med, Melbourne, Vic, Australia.;Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Melbourne, Vic, Australia..
    Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry2018In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 17, no 6, p. 530-538Article in journal (Refereed)
    Abstract [en]

    Background Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. Methods We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. Findings Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10.3%) of 1381 pregnancies for valproate, 19 (6.5%) of 294 for phenobarbital, eight (6.4%) of 125 for phenytoin, 107 (5 .5%) of 1957 for carbamazepine, six (3.9%) of 152 for topiramate, ten (3.0%) of 333 for oxcarbazepine, 74 (2.9%) of 2514 for lamotrigine, and 17 (2.8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0.0140), lamotrigine (p=0.0145), phenobarbital (13=0.0390), and valproate (p<0.0001). After adjustment, multivariable analysis showed that the prevalence of major congenital malformations was significantly higher for all doses of carbamazepine and valproate as well as for phenobarbital at doses of more than 80 mg/day than for lamotrigine at doses of 325 mg/day or less. Valproate at doses of 650 mg/day or less was also associated with increased risk of major congenital malformations compared with levetiracetam at doses of 250-4000 mg/day (odds ratio [OR] 2.43, 95% CI 1.30-4.55; p=0.0069). Carbamazepine at doses of more than 700 mg/day was associated with increased risk of major congenital malformations compared with levetiracetam at doses of 250-4000 mg/day (OR 2.41, 95% CI 1.33-4.38; p=0.0055) and oxcarbazepine at doses of 75-4500 mg/day (2.37, 1.17-4.80; 13=0.0169). Interpretation Different antiepileptic drugs and dosages have different teratogenic risks. Risks of major congenital malformation associated with lamotrigine, levetiracetam, and oxcarbazepine were within the range reported in the literature for offspring unexposed to antiepileptic drugs. These findings facilitate rational selection of these drugs, taking into account comparative risks associated with treatment alternatives. Data for topiramate and phenytoin should be interpreted cautiously because of the small number of exposures in this study. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

  • 47.
    Vasaitis, Lilian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Sengul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Gudjonsson, Olafur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurovetenskap.
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Casar Borota, Olivera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Histopathological findings in the landscape of IgG4-related pathology in patients with pituitary dysfunction: Review of six cases2021In: Journal of neuroendocrinology, ISSN 0953-8194, E-ISSN 1365-2826, Vol. 33, no 3, article id e12942Article in journal (Refereed)
    Abstract [en]

    IgG4-related hypophysitis (IgG4-RH) is increasingly being reported as an isolated entity or, less frequently, as a manifestation of a multiorgan IgG4-related disease (IgG4-RD), in which typical histopathology is a cornerstone for the diagnosis. We aimed to describe the histopathological changes in the surgical specimens from patients with clinical signs of pituitary disease that fulfilled the current diagnostic criteria for IgG4-RH. Histopathological features were correlated with clinical and radiological findings. Of 19 patients with pituitary dysfunction and inflammatory changes in the surgical pituitary specimen operated on during 2011-2019, we identified five patients with typical IgG4-related pathology (lymphoplasmacytic infiltration with more than 10 IgG4-positive plasma cells per one high power microscopic field, representing at least 40% of all plasma cells and at least focal storiform fibrosis). One patient with diabetes insipidus and pachymeningitis with IgG4-related changes in a biopsy from the dura was also included. Additional histopathological changes that typically are not part of the IgG4-RH were observed: Rathke's cleft cyst in four and granulomatous changes in two patients. One patient had an elevated serum IgG4 level and systemic manifestations that could be associated with the systemic IgG4-RD. Our findings indicate that pure IgG4-RH is uncommon. All patients with pituitary dysfunction, beyond typical IgG4-related pathology, had other pathological findings that could trigger the secondary IgG4-response. Both primary pathology and secondary IgG4-related features should be reported in patients with pituitary dysfunction because their co-occurrence may cause atypical clinical and imaging features, and unexpected response to surgical and pharmacological treatment. The current criteria for the diagnosis of IgG4-RH can lead to overdiagnosis of IgG4-RH if additional pathological changes are not taken into consideration. The classification criteria of IgG4-RD proposed by the American College of Rheumatology/European League Against Rheumatism could help classify patients more properly as IgG4-RH if applied to the pituitary gland.

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  • 48.
    Virhammar, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Jackmann, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Sköld, Mattias K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Kadir, Mohamed
    Frick, Jens
    Lindeberg, Jonas
    Olivero-Reinius, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Cunningham, Janet L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Grabowska, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Zetterberg, Henrik
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid2020In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 95, no 10, p. 445-449Article in journal (Refereed)
    Abstract [en]

    Here, we report a case of COVID-19–related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.

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  • 49.
    Virhammar, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Nääs, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Klang, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Ashton, Nicholas J
    Jackmann, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Westman, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Blennow, Kaj
    Zetterberg, Henrik
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity2021In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 28, no 10, p. 3324-3331Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID-19), and biomarkers of central nervous system (CNS) injury are reported to be increased in plasma but not extensively studied in cerebrospinal fluid (CSF). This study examined CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID-19.

    Methods: Nineteen patients with neurological symptoms and mild to critical COVID-19 were prospectively included. Extensive analysis of CSF, including measurement of biomarkers of CNS injury (neurofilament light chain [NfL] protein, glial fibrillary acidic protein [GFAp], and total tau), was performed and compared to neurological features and disease severity.

    Results: Neurological symptoms included altered mental status (42%), headache (42%), and central (21%) and peripheral weakness (32%). Two patients demonstrated minor pleocytosis, and four patients had increased immunoglobulin G levels in CSF. Neuronal autoantibody testing using commercial tests was negative in all patients. Increased CSF levels of NfL protein, total tau, and GFAp were seen in 63%, 37%, and 16% of patients, respectively. Increased NfL protein correlated with disease severity, time in intensive care, and level of consciousness. NfL protein in CSF was higher in patients with central neurological symptoms.

    Conclusions: Although limited by the small sample size, our data suggest that levels of NfL protein, GFAp, and total tau in CSF are commonly elevated in patients with COVID-19 with neurological symptoms. This is in contrast to the standard CSF workup where pathological findings are scarce. NfL protein, in particular, is associated with central neurological symptoms and disease severity.

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  • 50.
    Weber, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Gustafsson, Cecilia
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Malmgren, Kristina
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Strandberg, Moa
    Lund Univ Hosp, Dept Clin Sci, Dept Neurol, Lund, Sweden.
    Can, Umran
    Lund Univ Hosp, Dept Clin Sci, Dept Neurol, Lund, Sweden.
    Strandberg, Maria Compagno
    Lund Univ Hosp, Dept Clin Sci, Dept Neurol, Lund, Sweden.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Evaluation for epilepsy surgery - Why do patients not proceed to operation?2019In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 69, p. 241-244Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the reasons for not proceeding to surgery in patients undergoing presurgical evaluation for epilepsy. Methods: A retrospective cohort study of 401 consecutive patients who were evaluated for but did not proceed to surgery for epilepsy between 1990 and 2016 at three Swedish epilepsy surgery centers was performed. Reasons for not proceeding to surgery were categorized as inconclusive investigation, seizure onset within eloquent cortex, evidence of multiple seizure foci, infrequent seizures, risk of postoperative severe cognitive decline, patient or caregiver declining surgery or invasive investigation, severe psychiatric or somatic comorbidity, patient death during evaluation and complications during the evaluation. Chi-square tests were performed to compare ordered categorical variables. Results: During the entire time period the main reasons for rejection were inconclusive investigation (34,4%) and multifocal seizure onset (20,0%). The risk for severe cognitive decline postoperatively was more often a cause for rejection in more recent years. Patients declining invasive EEG or surgery accounted for a minor but not insignificant proportion (14,2%) of rejections. Conclusions: Inconclusive results from the presurgical evaluation and multifocal epilepsy were the main causes for not proceeding to surgery. The proportion of patients opting to abstain from surgery was low compared to other recent studies.

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