uu.seUppsala University Publications
Change search
Refine search result
2345678 201 - 250 of 465
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 201.
    Kagström, S.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Fält, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Demirbuker, S. Safer
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Berglund, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden.
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Svenningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden.
    Landtblom, Anne-Marie
    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.
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Sundström, P.
    Umea Univ, Dept Clin Neurosci, Umea, Sweden.
    Gunnarsson, M.
    Orebro Univ, Dept Neurol, Orebro, Sweden.
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of natalizumab (IMSE 1)2018In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 699-700Article in journal (Other academic)
  • 202. Khan, Taha
    et al.
    Grenholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Computer Vision Methods for Parkinsonian Gait Analysis: A Review onPatents2013In: Recent Patents on Biomedical Engineering, ISSN 1874-7647, Vol. 6, p. 97-108Article in journal (Refereed)
  • 203.
    Khan, Taha
    et al.
    Dalarna Univ, Sch Technol & Business Studies, S-79188 Falun, Sweden; Malardalen Univ, Sch Innovat Design & Technol, S-72123 Vasteras, Sweden.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Westin, Jerker
    Dalarna Univ, Sch Technol & Business Studies, S-79188 Falun, Sweden.
    Dougherty, Mark
    Dalarna Univ, Sch Technol & Business Studies, S-79188 Falun, Sweden.
    A computer vision framework for finger-tapping evaluation in Parkinson's disease2014In: Artificial Intelligence in Medicine, ISSN 0933-3657, E-ISSN 1873-2860, Vol. 60, no 1, p. 27-40Article in journal (Refereed)
    Abstract [en]

    Objectives: The rapid finger-tapping test (RFT) is an important method for clinical evaluation of movement disorders, including Parkinson's disease (PD). In clinical practice, the naked-eye evaluation of RFT results in a coarse judgment of symptom scores. We introduce a novel computer-vision (CV) method for quantification of tapping symptoms through motion analysis of index-fingers. The method is unique as it utilizes facial features to calibrate tapping amplitude for normalization of distance variation between the camera and subject. Methods: The study involved 387 video footages of RFT recorded from 13 patients diagnosed with advanced PD. Tapping performance in these videos was rated by two clinicians between the symptom severity levels ('0: normal' to '3: severe') using the unified Parkinson's disease rating scale motor examination of finger-tapping (UPDRS-FT). Another set of recordings in this study consisted of 84 videos of RFT recorded from 6 healthy controls. These videos were processed by a CV algorithm that tracks the index-finger motion between the video-frames to produce a tapping time-series. Different features were computed from this time series to estimate speed, amplitude, rhythm and fatigue in tapping. The features were trained in a support vector machine (1) to categorize the patient group between UPDRS-FT symptom severity levels, and (2) to discriminate between PD patients and healthy controls. Results: A new representative feature of tapping rhythm, 'cross-correlation between the normalized peaks' showed strong Guttman correlation (mu(2) = -0.80) with the clinical ratings. The classification of tapping features using the support vector machine classifier and 10-fold cross validation categorized the patient samples between UPDRS-FT levels with an accuracy of 88%. The same classification scheme discriminated between RFT samples of healthy controls and PD patients with an accuracy of 95%. Conclusion: The work supports the feasibility of the approach, which is presumed suitable for PD monitoring in the home environment. The system offers advantages over other technologies (e.g. magnetic sensors, accelerometers, etc.) previously developed for objective assessment of tapping symptoms.

  • 204.
    Klar, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sobol, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Mäbert, Katrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ameur, Adam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Johansson, Anna C V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Feuk, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Entesarian, Miriam
    Örlén, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Casar-Borota, Olivera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dahl, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Welander Distal Myopathy Caused by an Ancient Founder Mutation in TIA1 Associated with Perturbed Splicing.2013In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 34, no 4, p. 572-577Article in journal (Refereed)
    Abstract [en]

    Welander distal myopathy (WDM) is an adult onset autosomal dominant disorder characterized by distal limb weakness which progresses slowly from the fifth decade. All WDM patients are of Swedish or Finnish descent and share a rare chromosome 2p13 haplotype. We restricted the WDM associated haplotype followed by whole exome sequencing. Within the conserved haplotype we identified a single heterozygous mutation c.1150G>A (p.E384K) in TIA1 in all WDM patients investigated (n = 43). The TIA1 protein regulates splicing and translation through direct interaction with mRNA and the p.E384K mutation is located in the C-terminal Q-rich domain that interacts with the U1-C splicing factor. TIA1 has been shown to prevent skipping of SMN2 exon 7 and we show that WDM patients have increased levels of spliced SMN2 in skeletal muscle cells when compared to controls. Immunostaining of WDM muscle biopsies showed accumulation of TIA1 and stress granulae proteins adjacent to intracellular inclusions, a typical finding in WDM. The combined findings strongly suggest that the TIA1 mutation causes perturbed RNA splicing and cellular stress resulting in WDM. The selection against the mutation is likely to be negligible and the age of the TIA1 founder mutation was calculated to approximately 1050 years, which coincides with the epoch of early seafaring across the Baltic Sea.

  • 205.
    Kockum, Karin
    et al.
    Department of Pharmacology and Clinical Neuroscience, Neurology, Östersund, Umeå University, Umeå, Sweden.
    Lilja-Lund, Otto
    Department of Pharmacology and Clinical Neuroscience, Neurology, Östersund, Umeå University, Umeå, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Rosell, Michelle
    Department of Pharmacology and Clinical Neuroscience, Neurology, Östersund, Umeå University, Umeå, Sweden.
    Söderström, Lars
    Department of Pharmacology and Clinical Neuroscience, Neurology, Östersund, Umeå University, Umeå, Sweden.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Laurell, Katarina
    Department of Pharmacology and Clinical Neuroscience, Neurology, Östersund, Umeå University, Umeå, Sweden.
    The idiopathic normal-pressure hydrocephalus Radscale: a radiological scale for structured evaluation2018In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 3, p. 569-576Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Despite the important role of imaging in diagnosing idiopathic normal pressure hydrocephalus (iNPH), a structured overall assessment of radiological signs is still lacking. The purpose of this study was to construct a radiological scale, composed of morphological signs of iNPH, and compare it with clinical symptoms.

    METHODS: In this prospective, population based study of iNPH, 168 individuals (93 females, 75 males), mean age 75 years (range 66-92 years), underwent a computed tomography (CT) of the brain and a neurological examination with assessment of clinical symptoms according to Hellström's iNPH scale. Two radiologists, blinded to clinical data, independently evaluated and measured eight radiological parameters i.e. Evans' index, callosal angle, size of temporal horns, narrow high convexity sulci, dilated Sylvian fissures, focally dilated sulci, periventricular hypodensities and bulging of the lateral ventricular roof.

    RESULTS: In a linear regression model, all parameters except ventricular roof bulging were significantly associated with clinical iNPH symptoms. The seven remaining parameters were summarized into a total iNPH Radscale score ranging from 0 to 12. There was a significant correlation (r = 0.55, P < 0.001) between the total score of the iNPH Radscale and clinical symptoms. The interrater agreement for the included radiological parameters was high (ICC = 0.74-0.97).

    CONCLUSION: The iNPH Radscale may become a valuable diagnostic screening tool, allowing a structured radiological assessment. A high iNPH Radscale score together with clinical symptoms, should raise suspicion of iNPH motivating further evaluation for shunt-surgery.

  • 206. Kollberg, Gittan
    et al.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Holme, Elisabeth
    Oldfors, Anders
    Transient restoration of succinate dehydrogenase activity after rhabdomyolysis in iron-sulphur cluster deficiency myopathy2011In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 21, no 2, p. 115-120Article in journal (Refereed)
    Abstract [en]

    Myopathy with exercise intolerance and deficiency of iron sulphur cluster proteins is caused by an intronic IVS5+382 G > C mutation in ISCU, the gene encoding the iron sulphur cluster assembly protein (IscU). The mutation causes alternative splicing resulting in a truncated protein and severely reduced levels of IscU protein in muscle tissue. Disease manifestations include muscle fatigability, dyspnoea, cardiac palpitations and episodic myoglobinuria. Muscle tissue of these patients demonstrates marked histochemical succinate dehydrogenase deficiency and accumulation of iron in muscle fibres, which are morphological hallmarks of the disease. A biopsy specimen from a patient, two months after a severe attack of rhabdomyolysis, revealed regenerating muscle with normal succinate dehydrogenase activity and only minor iron accumulation, whereas another biopsy obtained nine years after the episode showed the typical hallmarks of the disease. The apparent explanation for the normal succinate dehydrogenase activity during regeneration was a markedly increased level of IscU protein in regenerating muscle tissue and an increase in normally spliced ISCU transcripts in the patient. The results have implications for diagnosis of the disease based on muscle biopsy findings and support the concept that an increase of normally spliced ISCU by RNA modulating therapy may be a therapeutic possibility for these patients.

  • 207. Kollberg, Gittan
    et al.
    Tulinius, Már
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Darin, Niklas
    Andersen, Oluf
    Holmgren, Daniel
    Oldfors, Anders
    Holme, Elisabeth
    Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy2009In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 132, no 8, p. 2170-2179Article in journal (Refereed)
    Abstract [en]

    Myopathy with deficiency of succinate dehydrogenase and aconitase is a recessively inherited disorder characterized by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, severe metabolic acidosis and rhabdomyolysis may occur. The disease has so far only been identified in northern Sweden. The clinical, histochemical and biochemical phenotype is very homogenous and the patients are homozygous for a deep intronic IVS5 382GC splicing affecting mutation in ISCU, which encodes the differently spliced cytosolic and mitochondrial ironsulphur cluster assembly protein IscU. Ironsulphur cluster containing proteins are essential for iron homeostasis and respiratory chain function, with IscU being among the most conserved proteins in evolution. We identified a shared homozygous segment of only 405 000 base pair with the deep intronic mutation in eight patients with a phenotype consistent with the original description of the disease. Two other patients, two brothers, had an identical biochemical and histochemical phenotype which is probably pathognomonic for muscle ironsulphur cluster deficiency, but they presented with a disease where the clinical phenotype was characterized by early onset of a slowly progressive severe muscle weakness, severe exercise intolerance and cardiomyopathy. The brothers were compound heterozygous for the deep intronic mutation and had a c.149 GA missense mutation in exon 3 changing a completely conserved glycine residue to a glutamate. The missense mutation was inherited from their mother who was of Finnish descent. The intronic mutation affects mRNA splicing and results in inclusion of pseudoexons in most transcripts in muscle. The pseudoexon inclusion results in a change in the reading frame and appearance of a premature stop codon. In western blot analysis of protein extracts from fibroblasts, there was no pronounced reduction of IscU in any of the patients, but the analysis revealed that the species corresponding to mitochondrial IscU migrates slower than a species present only in whole cells. In protein extracted from isolated skeletal muscle mitochondria the western blot analysis revealed a severe deficiency of IscU in the homozygous patients and appearance of a faint new fraction that could represent a truncated protein. There was only a slight reduction of mitochondrial IscU in the compound heterozygotes, despite their severe phenotype, indicating that the IscU expressed in these patients is non-functional.

  • 208. Kong, Wan-Yee
    et al.
    Tan, Benjamin Y Q
    Ngiam, Nicholas J H
    Tan, Deborah Y C
    Yuan, Christine H
    Holmin, Staffan
    Andersson, Tommy
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Teoh, Hock Luen
    Chan, Bernard P L
    Rathakrishnan, Rahul
    Ting, Eric Y S
    Sharma, Vijay K
    Yeo, Leonard L L
    Validation of Serial Alberta Stroke Program Early CT Score as an Outcome Predictor in Thrombolyzed Stroke Patients.2017In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 26, no 10, p. 2264-2271, article id S1052-3057(17)30227-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) on baseline imaging is an established predictor of functional outcome in anterior circulation acute ischemic stroke (AIS). We studied ASPECTS before intravenous thrombolysis (IVT) and at 24 hours to assess its prognostic value.

    METHODS: Data for consecutive anterior circulation AIS patients treated with IVT from 2006 to 2013 were extracted from a prospectively managed registry at our tertiary center. Pre-thrombolysis and 24-hour ASPECTS were evaluated by 2 independent neuroradiologists. Outcome measures included symptomatic intracranial hemorrhage (SICH), modified Rankin Scale (mRS) at 90 days, and mortality. Unfavorable functional outcome was defined by mRS >1. Dramatic ASPECTS progression (DAP) was defined as deterioration in ASPECTS by 6 points or more.

    RESULTS: Of 554 AIS patients thrombolyzed during the study period, 400 suffered from anterior circulation infarction. The median age was 65 years (interquartile range (IQR): 59-70) and the median National Institutes of Health Stroke Scale score was 18 points (IQR: 12-22). Compared with the pre-IVT ASPECTS (area under the curve [AUC] = .64, 95% confidence interval [CI]: .54-.65, P = .001), ASPECTS on the 24-hour CT scan (AUC = .78, 95% CI: .73-.82, P < .001), and change in ASPECTS (AUC = .69, 95% CI: .64-.74, P < .001) were better predictors of unfavorable functional outcome at 3 months. DAP, noted in 34 (14.4%) patients with good baseline ASPECTS (8-10 points), was significantly associated with unfavorable functional outcome (odds ratio [OR]: 9.91, 95% CI: 3.37-29.19, P ≤ .001), mortality (OR: 21.99, 95% CI: 7.98-60.58, P < .001), and SICH (OR: 8.57, 95% CI: 2.87-25.59, P < .001).

    CONCLUSION: Compared with the pre-thrombolysis score, ASPECTS measured at 24 hours as well as serial change in ASPECTS is a better predictor of 3-month functional outcome.

  • 209.
    Kumlien, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Akutneurologi2012In: Neurologi / [ed] Fagius J, Nyholm D, Liber, 2012Chapter in book (Other (popular science, discussion, etc.))
  • 210.
    Kundu, Soumi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Xiong, Anqi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Spyrou, Argyris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wicher, Grzegorz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Marinescu, Voichita D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Zhang, Lei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dimberg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Ilan, Neta
    Technion, Ruth & Bruce Rappaport Fac Med, Canc & Vasc Biol Res Ctr, Haifa, Israel.
    Vlodavsky, Israel
    Technion, Ruth & Bruce Rappaport Fac Med, Canc & Vasc Biol Res Ctr, Haifa, Israel.
    Li, Jin-Ping
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Forsberg-Nilsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Heparanase Promotes Glioma Progression and is Inversely Correlated with Patient Survival.2016In: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 14, no 12, p. 1243-1253Article in journal (Refereed)
    Abstract [en]

    Malignant glioma continues to be fatal, despite improved insight into its underlying molecular mechanisms. The most malignant form, glioblastoma (GBM), is characterized by aberrant activation of receptor tyrosine kinases (RTK) and infiltrative growth. Heparan sulfate proteoglycans (HSPGs), integral components of the extracellular matrix of brain tumors (HPSE), which cleaves HSPGs, for its role in glioma. This hypothesis was evaluated using tissue microarrays, GBM cells derived from patients, murine in vitro and in vivo can regulate activation of many RTK pathways. This prompted us to investigate heparanase models of glioma, and public databases. Down-regulation of HPSE attenuated glioma cell proliferation, while addition of HPSE stimulated growth, and activated ERK and AKT signaling. Using HPSE transgenic and knockout mice it was demonstrated that tumor development in vivo was positively correlated to HPSE levels in the brain. HPSE also modified the tumor microenvironment, influencing reactive astrocytes, microglia/monocytes and tumor angiogenesis. Furthermore, inhibition of HPSE reduces tumor cell numbers, both in vitro and in vivo. HPSE was highly expressed in human glioma and GBM cell lines, compared to normal brain tissue. Indeed, a correlation was observed between high levels of HPSE and shorter survival of patients with high-grade glioma. In conclusion, these data provide proof-of-concept for anti-HPSE treatment of malignant glioma, as well as novel insights for the development of HPSE as a therapeutic target.

    IMPLICATIONS: This study aims to target both the malignant brain tumor cells per se, and their microenvironment by changing the level of an enzyme, heparanase, that breaks down modified sugar chains on cell surfaces and in the extracellular space.

  • 211.
    Kågström, S.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Fält, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Demirbuker, S. Safer
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Berglund, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden.
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Svenningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden.
    Landtblom, A. -M
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Sundström, P.
    Umea Univ, Dept Clin Neurosci, Umea, Sweden.
    Gunnarsson, M.
    Orebro Univ, Dept Neurol, Orebro, Sweden.
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Real-world longitudinal data of peginterferon beta-1a from a Swedish national post-marketing surveillance study (IMSE 6) - efficacy and safety profile2018In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 927-928Article in journal (Other academic)
  • 212. Lallukka, Tea
    et al.
    Ervasti, Jenni
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Mittendorfer-Rutz, Ellenor
    Friberg, Emilie
    Virtanen, Marianna
    Alexanderson, Kristina
    Trends in Diagnosis-Specific Work Disability Before and After Stroke: A Longitudinal Population-Based Study in Sweden.2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e006991Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although a stroke event often leads to work disability, diagnoses behind work disability before and after stroke are largely unknown. We examined the pre-event and postevent trends in diagnosis-specific work disability among patients of working age.

    METHODS AND RESULTS: We included all new nonfatal stroke events in 2006-2008 from population-based hospital registers in Sweden among women and men aged 25 to 60 years (n=12 972). Annual days of diagnosis-specific work disability were followed for 4 years before and after stroke. Repeated measures negative binomial regression models using the generalized estimating equations method were fitted to examine trends in diagnosis-specific work disability before and after the event. Already during the 4 pre-event years, work disability attributed to circulatory diseases increased among women (rate ratio, 1.99; 95% confidence interval, 1.68-2.36) and men (rate ratio, 2.20; 95% confidence interval, 1.88-2.57). Increasing trends before stroke were also found for work disability attributed to mental disorders, musculoskeletal diseases, neoplasms, diseases of the nervous, respiratory, and digestive systems, injuries, and diabetes mellitus. As expected, a sharp increase in work disability days attributed to circulatory diseases was found during the first year after the event among both sexes. Overall, during 4 years after the stroke, there was a decreasing trend for circulatory diseases and injuries, whereas the trend was increasing for nervous diseases and diabetes mellitus.

    CONCLUSIONS: Work disability attributed to several mental and somatic diagnoses is higher already before a stroke event.

  • 213. Landtblom, A. -M
    et al.
    Katsarogiannis, Evangelos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kristoffersson, A.
    Linkoping Univ, Motala Gen Hosp, Motala, Sweden.
    Berntsson, S. Ghaderi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Semnic, R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Boström, I.
    Linkoping Univ, Neurol, Linkoping, Sweden.
    Challenges in diagnosing OCB-negative MS - the importance of imaging2018In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 743-743Article in journal (Other academic)
  • 214.
    Landtblom, Anne-Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Engström, Maria
    Brain circuitries involved in sleep disorders2015In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, article id UNSP 66Article in journal (Refereed)
  • 215.
    Landtblom, Anne-Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Linkoping Univ, Div Neurol, Dept Clin & Expt Med, IKE,Cty Council, Linkoping, Sweden; Linkoping Univ, Cty Council, IMM,Neurol Unit, Dept Med Specialties, Motala, Sweden; Linkoping Univ, Dept Med & Hlth Sci, Div Radiol Sci, Linkoping, Sweden.
    Engström, Maria
    Linkoping Univ, Dept Med & Hlth Sci, Div Radiol Sci, Linkoping, Sweden.
    The sleepy teenager: diagnostic challenges OCR V262014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 140Article in journal (Refereed)
    Abstract [en]

    The sleepy teenager puts the doctor in a, often tricky, situation where it must be decided if we deal with normal physiology or if we should suspect pathological conditions. What medical investigations are proper to consider? What differential diagnoses should be considered in the first place? And what tools do we actually have? The symptoms and problems that usually are presented at the clinical visit can be both of medical and psychosocial character - and actually they are often a mixture of both. Subsequently, the challenge to investigate the sleepy teenager often includes the examination of a complex behavioral pattern. It is important to train and develop diagnostic skills and to realize that the physiological or pathological conditions that can cause the symptoms may have different explanations. Research in sleep disorders has shown different pathological mechanisms congruent with the variations in the clinical picture. There are probably also different patterns of involved neuronal circuits although common pathways may exist. The whole picture remains to be drawn in this interesting and challenging area.

  • 216.
    Landtblom, Anne-Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Guala, D.
    Merck GmbH, Stockholm, Sweden..
    Hau, S.
    Malmo Hosp, Malmo, Sweden..
    Jansson, L.
    UAS, Akad Hosp, Neurol Clin, Uppsala, Sweden..
    Martin, C.
    Danderyd Hosp, Neurol, Danderyd, Sweden..
    Fredrikson, S.
    Karolinska Inst, Neurosci, Stockholm, Sweden..
    RebiQoL: A telemedicine patient support program on health related quality of life and adherence in MS patients treated with Rebif2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, p. 425-425Article in journal (Other academic)
  • 217.
    Landtblom, Anne-Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kristoffersson, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Univ Linkoping, Gen Hosp, Neurol Policlin, Motala, Sweden..
    Jansson, L.
    UAS, Neurol Clin, Akad Hosp, Uppsala, Sweden..
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Bostrom, I.
    Linkoping Univ, Clin & Expt Med, Linkoping, Sweden..
    Berntsson, S. Ghaderi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. UAS, Neurol Clin, Akad Hosp, Uppsala, Sweden..
    The diagnosis of OCB-negative MS-patients - an inventory of the Swedish MS register in Uppsala, Sweden2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, p. 439-439Article in journal (Other academic)
  • 218. Langenkamp, Elise
    et al.
    Zhang, Lei
    Lugana, Roberta
    Huang, Hua
    Elsir, Tomador
    Bazzar, Wesam
    Lööf, Johan
    Trendelenburg, George
    Pontén, Fredrik
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Dimberg, Anna
    High expression of the C-type lectin CD93 in glioblastoma vasculature enhancesvessel function by regulating cytoskeletal rearrangements and leads to poor survival2015In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445Article in journal (Other academic)
  • 219.
    Langenkamp, Elise
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Zhang, Lei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lugano, Roberta
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Huang, Hua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Elhassan, Tamador Elsir Abu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Georganaki, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Bazzar, Wesam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lööf, Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Trendelenburg, George
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Dimberg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Elevated Expression of the C-Type Lectin CD93 in the Glioblastoma Vasculature Regulates Cytoskeletal Rearrangements That Enhance Vessel Function and Reduce Host Survival2015In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 75, no 21, p. 4504-4516Article in journal (Refereed)
    Abstract [en]

    Glioblastoma is an aggressive brain tumor characterized by an abnormal blood vasculature that is hyperpermeable. Here, we report a novel role for CD93 in regulating angiogenesis in this setting by modulating cell-cell and cell-matrix adhesion of endothelial cells. Tissue microarray analysis demonstrated that vascular expression of CD93 was correlated with poor survival in a clinical cohort of patients with high-grade astrocytic glioma. Similarly, intracranial growth in the GL261 mouse model of glioma was delayed significantly in CD93(-/-) hosts, resulting in improved survival compared with wild-type mice. This effect was associated with increased vascular permeability and decreased vascular perfusion of tumors, indicating reduced vessel functionality in the absence of CD93. RNAi-mediated attenuation of CD93 in endothelial cells diminished VEGF-induced tube formation in a three-dimensional collagen gel. CD93 was required for efficient endothelial cell migration and proper cell polarization in vitro. Further, in endothelial cells where CD93 was attenuated, decreased cell spreading led to a severe reduction in cell adhesion, a lack of proper cell contacts, a loss of VE-cadherin, and aberrant actin stress fiber formation. Our results identify CD93 as a key regulator of glioma angiogenesis and vascular function, acting via cytoskeletal rearrangements required for cell-cell and cell-matrix adhesion.

  • 220.
    Larsson, Birgitta Jakobsson
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Fröjd, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Nygren, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Relatives of patients with amyotrophic lateral sclerosis: Their experience of care and support2015In: Palliative & Supportive Care, ISSN 1478-9515, E-ISSN 1478-9523, Vol. 13, no 6, p. 1569-1577Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The purpose of this study was to describe relatives' experience of patient care and the support they themselves received during the course of disease progression.

    METHOD: A total of 15 relatives were included from two neurology clinics in Sweden: 7 wives, 4 husbands, and 4 daughters. Data were collected through qualitative interviews 6 to 12 months after the patient had died. Content analysis was performed to analyze the interviews.

    RESULT: The results showed that patient care was experienced as positive and as being based on the patient's needs and desires. Treatment from the staff, support and help, knowledge, availability, and continuity among the team were important reasons for the relations to feel secure. In addition, support for relatives was available, but different factors influenced its use. Most relatives did not think about their own needs but focused on the patient.

    SIGNIFICANCE OF RESULTS: It is important that care and support for both patients and relatives be based on individual needs. The staff members responsible for providing this care and support must have knowledge and experience of the disease and its specific care. If they do not belong to an ALS (amyotrophic lateral sclerosis) team, they may require further education and support. The relatives focus on the patient's situation and do not think of their own needs. It is therefore important that health professionals be observant of the relatives and offer them help and support to better manage their situation.

  • 221.
    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.

  • 222.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Berntsson, Shala G.
    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.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    A novel radiological classification system for cerebral gliomas: The Brain-Grid2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 1, article id e0211243Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Standard radiological/topographical classifications of gliomas often do not reflect the real extension of the tumor within the lobar-cortical anatomy. Furthermore, these systems do not provide information on the relationship between tumor growth and the subcortical white matter architecture. We propose the use of an anatomically standardized grid system (the Brain-Grid) to merge serial morphological magnetic resonance imaging (MRI) scans with a representative tractographic atlas. Two illustrative cases are presented to show the potential advantages of this classification system.

    METHODS: MRI scans of 39 patients (WHO grade II and III gliomas) were analyzed with a standardized grid created by intersecting longitudinal lines on the axial, sagittal, and coronal planes. The anatomical landmarks were chosen from an average brain, spatially normalized to the Montreal Neurological Institute (MNI) space and the Talairach space. Major white matter pathways were reconstructed with a deterministic tracking algorithm on a reference atlas and analyzed using the Brain-Grid system.

    RESULTS: In all, 48 brain grid voxels (areas defined by 3 coordinates, axial (A), coronal (C), sagittal (S) and numbers from 1 to 4) were delineated in each MRI sequence and on the tractographic atlas. The number of grid voxels infiltrated was consistent, also in the MNI space. The sub-cortical insula/basal ganglia (A3-C2-S2) and the fronto-insular region (A3-C2-S1) were most frequently involved. The inferior fronto-occipital fasciculus, anterior thalamic radiation, uncinate fasciculus, and external capsule were the most frequently associated pathways in both hemispheres.

    CONCLUSIONS: The Brain-Grid based classification system provides an accurate observational tool in all patients with suspected gliomas, based on the comparison of grid voxels on a morphological MRI and segmented white matter atlas. Important biological information on tumor kinetics including extension, speed, and preferential direction of progression can be observed and even predicted with this system. This novel classification can easily be applied to both prospective and retrospective cohorts of patients and increase our comprehension of glioma behavior.

  • 223.
    Laurell, Katarina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Neurology.
    Headache in Schoolchildren: Epidemiology, Pain Comorbidity and Psychosocial Factors2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Headache is the most frequently reported pain in children and is associated with missed schooldays, anxiety, depressive symptoms and various physical symptoms. A secular trend of increasing headache prevalence has been suggested. Few studies have focused on tension-type headache among children from the general population.

    The aims of this thesis were to describe the prevalence, incidence and prognosis of tension-type headache, migraine and overall headache in schoolchildren, to identify medical, psychological and social factors associated with these headache types, and to determine whether the prevalence of headache has increased over the last decades.

    In 1997, 1850 schoolchildren aged 7-15 years from the city of Uppsala participated in a questionnaire study and 1371 (74.1%) responded. Out of these, a randomly selected, stratified sample of 131 children and their parents were interviewed. Three years later, 122 children from the interview sample replied to an identical headache questionnaire.

    Compared with a similar study in 1955, a significantly lower proportion of schoolchildren reported no headache. The prevalence of tension-type headache increased with age and was significantly higher in girls than boys after the age of twelve. Similar age and gender differences were obtained for migraine. A higher proportion of girls reported frequent headache than boys. Children with headache, especially those with migraine, as well as their first-degree relatives suffered from other pains and physical symptoms more frequently than headache-free children and their first-degree relatives. Although the likelihood of experiencing the same headache diagnosis and symptoms at follow-up was high, about one fifth of children with migraine developed tension-type headache and vice versa. Female gender was a predictor of migraine and frequent headache a predictor of overall headache at follow-up. The estimated annual incidence for tension-type headache, migraine and overall headache was 81, 65 and 131 per 1000 children, respectively.

    In conclusion, the results indicate that headache has become increasingly common among schoolchildren over the last decades. Prevention and treatment of headache is particularly important for girls since they have high prevalence of headache, frequent headache episodes and a poor outcome. In children with headache, diagnoses and treatment should be reassessed regularly and other pains should be asked about and treated as well.

    List of papers
    1. Headache in schoolchildren:agreement between different sources of information
    Open this publication in new window or tab >>Headache in schoolchildren:agreement between different sources of information
    2003 In: Cephalalgia, ISSN 0333-1024, Vol. 23, p. 420-428Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-93208 (URN)
    Available from: 2005-05-17 Created: 2005-05-17Bibliographically approved
    2. Prevalence of headache in Swedish schoolchildren, with a focus on tension-type headache
    Open this publication in new window or tab >>Prevalence of headache in Swedish schoolchildren, with a focus on tension-type headache
    2004 In: Cephalalgia, ISSN 0333-1024, Vol. 24, p. 380-388Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-93209 (URN)
    Available from: 2005-05-17 Created: 2005-05-17Bibliographically approved
    3. Headache in schoolchildren: association with other pain, family history and psychosocial factors
    Open this publication in new window or tab >>Headache in schoolchildren: association with other pain, family history and psychosocial factors
    Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-93210 (URN)
    Available from: 2005-05-17 Created: 2005-05-17Bibliographically approved
    4. A 3-year follow-up of headache diagnoses and symptoms in Swedish schoolchildren
    Open this publication in new window or tab >>A 3-year follow-up of headache diagnoses and symptoms in Swedish schoolchildren
    Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-93211 (URN)
    Available from: 2005-05-17 Created: 2005-05-17Bibliographically approved
  • 224.
    Laurell, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Klassifikation, förekomst och prognos2009In: Migrän och spänningshuvudvärk hos barn och tonåringar / [ed] Bo Larsson, Lund: Studentlitteratur , 2009, 2, p. 23-30Chapter in book (Other academic)
  • 225.
    Laurell, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Artto, V.
    Bendtsen, L.
    Hagen, K.
    Kallela, M.
    Meyer, E. Laudon
    Putaala, J.
    Tronvik, E.
    Zwart, J. -A
    Linde, M.
    Migrainous infarction: a Nordic multicenter study2011In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 18, no 10, p. 1220-1226Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Migrainous infarction (MI), i.e. an ischemic stroke developing during an attack of migraine with aura is rare and the knowledge of its clinical characteristics is limited. Previous case series using the International Classification of Headache Disorders (ICHD) included < 10 cases which make conclusions less valid. This study aimed to describe characteristics and outcome of MI in a larger sample.

    Methods: We analyzed demographic data, risk factors, migraine medication, stroke localization, symptoms, and outcome in a sample of 33 patients with MI according to second edition of the ICHD criteria collected from seven Nordic headache clinics.

    Results: Amongst 33 patients with MI, there were 20 (61%) women and 13 (39%) men with the median age for stroke of 39 (range 19-76) years. Traditional risk factors for stroke were rare compared with Scandinavian young ischemic stroke populations. During the acute phase, 12 (36%) patients used ergotamines or triptans. Stroke was located in the posterior circulation in 27 (82%) patients and cerebellum was involved in 7 (21%). Except in two patients with brainstem infarctions, the outcome was favorable with total recovery or limited residual symptoms.

    Conclusions: The prevalence of traditional risk factors was low and the infarctions were predominantly located in posterior circulation territory, supporting theories of migraine specific mechanisms. The outcome was in general favorable.

  • 226.
    Laurell, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Bo
    Eeg-Olofsson, Orvar
    Headache in schoolchildren: association with other pain, family history and psychosocial factorsArticle in journal (Refereed)
  • 227.
    Laurell, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Bo
    Eeg-Olofsson, Orvar
    Headache in schoolchildren:agreement between different sources of information2003In: Cephalalgia, ISSN 0333-1024, Vol. 23, p. 420-428Article in journal (Refereed)
  • 228.
    Laurell, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Bo
    Eeg-Olofsson, Orvar
    Prevalence of headache in Swedish schoolchildren, with a focus on tension-type headache2004In: Cephalalgia, ISSN 0333-1024, Vol. 24, p. 380-388Article in journal (Refereed)
  • 229.
    Laurell, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Bo
    Mattsson, Peter
    Eeg-Olofsson, Orvar
    A 3-year follow-up of headache diagnoses and symptoms in Swedish schoolchildrenArticle in journal (Refereed)
  • 230.
    Laurell, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Migrainous Infarction: Aspects on Risk Factors and Therapy2012In: Current Pain and Headache Reports, ISSN 1531-3433, E-ISSN 1534-3081, Vol. 16, no 3, p. 255-260Article, review/survey (Refereed)
    Abstract [en]

    Migraine and stroke are related in more than one way. Migraine with aura is a risk factor for ischemic stroke in women under age 45 years, particularly when combined with other risk factors such as smoking and oral contraceptives. Further, individuals with migraine with aura seem to have more white matter lesions and ischemic infarctions than control patients. Migraine has been correlated to cervical artery dissection, the symptoms of which can mimic migraine. Correspondingly, migraine with aura sometimes is mistaken for stroke. Migrainous infarction is a rare but specific type of ischemic stroke developing during an attack of migraine with aura. It is important to recognize this unusual complication of migraine because the management probably is important. In this review, we will discuss the present knowledge of migrainous infarction, the clinical picture, possible mechanisms, and potential prevention and treatment.

  • 231.
    Leandersson, A.
    et al.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Kagstrom, S.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Forsberg, L.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Hillert, J.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden..
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Svenningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Landtblom, Anne-Marie
    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.
    Walentin, F.
    Orebro Univ Hosp, Orebro, Sweden..
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Piehl, F.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3)2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, p. 888-889Article in journal (Other academic)
  • 232.
    Leandersson, A.
    et al.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Kagstrom, S.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Forsberg, L.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Hillert, J.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden..
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Svenningsson, A.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Landtblom, Anne-Marie
    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.
    Walentin, F.
    Orebro Univ Hosp, Orebro, Sweden..
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Piehl, F.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of fingolimod (IMSE 2)2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, p. 374-375Article in journal (Other academic)
  • 233.
    Lenngren Hysing, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Handläggning av cerebellär infarkt, basilaristrombos samt karotis- och vertebralisdissektion2007Student paper other, 5 credits / 7,5 HE creditsStudent thesis
  • 234.
    Libard, Sylwia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Popova, Svetlana N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Kärjä, Vesa
    Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
    Pietiläinen, Timo
    Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
    Hämäläinen, Kirsi M
    Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Department of Neurosurgery, Uppsala University Hospital, Sweden.
    Bergqvist, Michael
    Department of radiation sciences, Umeå University, Sweden.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Pfeifer, Susan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    de Ståhl, Teresita Diaz
    Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, p. e108861-Article in journal (Refereed)
    Abstract [en]

    Human cytomegalovirus (HCMV) has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC) methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.

  • 235. Link, Hans
    et al.
    Huang, Yu-Min
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Oligoclonal bands in multiple sclerosis cerebrospinal fluid: An update on methodology and clinical usefulness2006In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 180, no 1-2, p. 17-28Article in journal (Refereed)
    Abstract [en]

    Two or more oligoclonal IgG bands (OB) detected by separation of cerebrospinal fluid (CSF) proteins while not demonstrable in corresponding serum reflect a local B-cell response accompanying central nervous system (CNS) inflammation. Using optimized, standardized methodology, preferentially protein separation by isoelectric focusing followed by immunoblotting, more than 95% of patients with multiple sclerosis (MS) have CSF OB of IgG class not detectable in serum, thereby providing powerful evidence for the diagnosis of MS. Once present, CSF OB persists in the individual patient irrespective of MS course or therapy. Because of the high sensitivity of CSF OB in MS as well as its high specificity in the appropriate clinical setting, examination of CSF for OB of IgG class can be strongly recommended to obtain support for the diagnosis of MS and identify patients with clinically isolated syndrome (CIS) at increased risk of developing MS. The IgG index equal to CSF/serum IgG: CSF/serum albumin is elevated in about 70% of MS patients, but rarely in CSF OB-negative MS. Because of lower diagnostic sensitivity, IgG index cannot be recommended as replacement of CSF OB in the diagnosis of MS but, when elevated, as additional evidence for an augmented B-cell response within the CNS that is compatible with MS. Although the clinical picture as well as findings from magnetic resonance imaging of the brain and spinal cord are essential for an MS diagnosis, this should be re-evaluated in CSF OB-negative patients, keeping in mind the many disease entities imitating MS. Recommended diagnostic criteria for MS must include definitions of the role of lumbar puncture and of clearly specified, optimized and standardized routine CSF investigations including for the presence of CSF IgG OB. There is a need for concerted long-term follow-up studies of the subgroup of MS patients without CSF OB regarding e.g. prognostic and immunologic features. For inclusion in trials of disease-modulating drugs, it is recommended that patients with MS or CIS are selected regarding presence vs. absence of CSF OB. Development and evaluation of new technologies to define local vs. systemic B-cell responses in patients with MS or CIS vs. patients with other inflammatory neurological diseases should shed new light on the role of CSF OB, which remains enigmatic.

  • 236.
    Lourenco, F.
    et al.
    Hosp Curry Cabral, Autoimmune Dis Unit, CHLC, Lisbon, Portugal..
    Katsarogiannis, Evangelos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Berntsson, Shala
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Moraes-Fontes, M. F.
    Hosp Curry Cabral, Autoimmune Dis Unit, CHLC, Lisbon, Portugal..
    Systemic Lupus Erythematous and Progressive Multifocal Leukoencephalopathy: focus on lymphopenia2015In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 33, no 3, p. S33-S33Article in journal (Other academic)
  • 237.
    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

  • 238.
    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)
  • 239.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Widström, Charles
    Uppsala Univ Hosp, Uppsala, Sweden.
    Jonasson, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Appel, Lieuwe
    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. Uppsala Univ Hosp, Uppsala, Sweden.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala Univ Hosp, Uppsala, Sweden.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Differential diagnosis of patients with parkinsonian syndrome using multilinear regression to disease-specific C-11-PE2I-PET templates and classification tree learning2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S409-S409Article in journal (Other academic)
  • 240.
    Lugano, Roberta
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Vemuri, Kalyani
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Yu, Di
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Johansson, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Dejana, Elisabetta
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Dimberg, Anna
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    CD93 promotes β1 integrin activation and fibronectin fibrillogenesis during tumor angiogenesis.2018In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 128, no 8, p. 3280-3297Article in journal (Refereed)
    Abstract [en]

    Tumor angiogenesis occurs through regulation of genes that orchestrate endothelial sprouting and vessel maturation, including deposition of a vessel-associated extracellular matrix. CD93 is a transmembrane receptor that is up-regulated in tumor vessels in many cancers, including high-grade glioma. Here, we demonstrate that CD93 regulates integrin-β1-signaling and organization of fibronectin fibrillogenesis during tumor vascularization. In endothelial cells and mouse retina, CD93 was found to be expressed in endothelial filopodia and to promote filopodia formation. The CD93 localization to endothelial filopodia was stabilized by interaction with multimerin-2 (MMRN2), which inhibited its proteolytical cleavage. The CD93-MMRN2 complex was required for activation of integrin-β1, phosphorylation of focal adhesion kinase (FAK) and fibronectin fibrillogenesis in endothelial cells. Consequently, tumor vessels in gliomas implanted orthotopically in CD93-deficient mice showed diminished activation of integrin-β1 and lacked organization of fibronectin into fibrillar structures. These findings demonstrate a key role of CD93 in vascular maturation and organization of the extracellular matrix in tumors, identifying it as a potential target for therapy.

  • 241. Lundin, Anders
    et al.
    Dietrichs, Espen
    Haghighi, Sara
    Göller, Marine-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Heiberg, Arvid
    Loutfi, Ghada
    Widner, Håkan
    Wiktorin, Klas
    Wiklund, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Svenningsson, Anders
    Sonesson, Clas
    Waters, Nicholas
    Waters, Susanna
    Tedroff, Joakim
    Efficacy and Safety of the Dopaminergic Stabilizer Pridopidine (ACR16) in Patients With Huntington's Disease2010In: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 33, no 5, p. 260-264Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate the efficacy and safety of the dopaminergic stabilizer pridopidine (ACR16) in patients with Huntington's disease (HD). Methods: In a randomized, double-blind, placebo-controlled, 4-week trial, patients with HD received pridopidine (50 mg/d, n = 28) or placebo (n = 30). The primary outcome measure was the change from baseline in weighted cognitive score, assessed by cognitive tests (Symbol Digit Modalities, verbal fluency, and Stroop tests). Secondary outcome measures included changes in the Unified Huntington's Disease Rating Scale, Hospital Anxiety and Depression Scale, Leeds Sleep Evaluation Questionnaire, Reitan Trail-Making Test A, and Clinical Global Impression of Change. Safety assessments were also performed. Results: There was no significant difference between pridopidine and placebo in the change from baseline of the weighted cognitive score. However, secondary measures such as affective symptoms showed trends toward improvement, and there was significant improvement in voluntary motor symptoms compared with placebo (P<0.05). Pridopidine was well tolerated, with a safety profile similar to placebo. Conclusions: Pridopidine shows promise as a treatment for some of the symptoms of HD. In this small-scale study, the most notable effect was improvement in voluntary motor symptoms. Larger, longer-term trials are warranted.

  • 242.
    Lundström, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    International Comparisons of Stroke Costs Are Always Limited2010In: Stroke, Vol. 41, no 7, p. e472-e472Article in journal (Refereed)
  • 243.
    Lundström, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Medicinsk behandling av cervical dissektion2017In: Neurologi i Sverige, E-ISSN 2002-9004, no 2, p. 58-62Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Dissektion av hjärnans arteriella kärl är en vanlig orsak till stroke hos unga personer. Denna artikel av Erik Lundström, docent och sektionsöverläkare i neurologi, Karolinska Universitetssjukhuset, Solna, fokuserar på frågor som rör den medicinska behandlingen av halskärlsdissektion.

    Dissektion av hjärnans arteriella kärl är den vanligaste kända orsaken till stroke hos yngre individer.1 Medelåldern är 45 år med en viss övervikt av män.2 Hälften av alla individer har haft någon form av trauma mot halsen. Patienter med cervikal artärdissektion har oftare högre blodtryck men samtidigt lägre förekomst av hyperkolesterolemi än matchade friska kontroller. Migrän – särskilt med aura – och hyperhomocystemi har identifierats som riskfaktorer. Anamnes på nyligen genomgången infektion ökar risken och detta kan delvis förklara den säsongsvariation som förekommer. Populationsbaserade studier uppskattar incidensen av cervikal dissektion till ungefär 3 per 100 000 individer och år varav hälften drabbas av en stroke eller TIA.3 I Sverige skulle det innebära att 300 individer varje år får cervikal dissektion och att 150 drabbas av stroke eller TIA. Dissektionen kan vara extrakraniell, dvs förekomma i arteria carotis interna eller arteria vertebralis fram till dess inträde i kraniet, eller intrakraniell, dvs förekomma i ett kärl inne i hjärnan. Det är erkänt svårt att ställa diagnosen intrakraniell dissektion och jag har inte hittat några bra uppgifter på hur stor andel just den delen utgör av det totala antalet dissektioner. Denna artikel fokuserar på medicinsk behandling av cervikal dissektion och tar upp några vanliga frågor som jag får som stroke-profilerad neurolog: ”Törs vi ge intravenös trombolys vid en dissektion? Ska vi ge acetylsalicylsyra eller warfarin som sekundärprofylax? Hur lång tid ska vi behandla?” Råden anknyter till de nyligen publicerade rekommendationerna från Karolinska Stroke Update, november 20164 där undertecknad var sekreterare i avsnittet om halskärlsdissektion. De nationella riktlinjerna för stroke kommer att presenteras under 2017, men jag har ingen förhandsinformation om vad de kommer att ge för rekommendationer inom detta område.

  • 244.
    Lundström, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Response to Letter by Dobkin2010In: Stroke, Vol. 41, no 7, p. e471-e471Article in journal (Refereed)
  • 245.
    Lundström, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Trombektomi vid ischemisk stroke: ett paradigmskifte inom akut strokebehandling2015In: Neurologi i Sverige, Vol. 2015, no 4, p. 14-20Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Trombektomi är en endovaskulär metod där man med kateter mekaniskt avlägsnar en propp i hjärnan. Mycket talar för att trombektomi är det viktigaste som har hänt inom stroke de senaste 20 åren, ett paradigmskifte inom akut strokebehandling. I denna översiktsartikel sammanfattar Erik Lundström, sektionsöverläkare vid Neurologkliniken, Karolinska Universitetssjukhuset, Solna, bevisläget för trombektomi vid ischemisk stroke

  • 246.
    Lundström, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Trombektomi är möjlig upp till 24 timmar efter stroke: Om man väljer rätt patient2018In: Neurologi i Sverige, no 2, p. 50-53Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    År 2015 publicerades den epokgörande studien MR CLEAN1 som visade att trombektomi vid stroke i den främre cirkulationen fungerade inom upp till 6 timmar. Därefter har ytterligare studier bekräftat resultatet. En metaanalys av fem studier har visat att trombektomi inom 6 timmar av patienter med ocklusion av de stora kärlen i den främre cirkulationen är en högeffektiv behandling. Trombektomi innebär att dubbelt så många patienter kan få ett oberoende liv jämfört med de som enbart får trombolys. Sammantaget har detta inneburit att trombektomi inom 6 timmar har fått den högsta prioriteringen i de svenska strokeriktlinjerna. Under senaste året har det tillkommit ytterligare två trombektomistudier – DAWN och DEFUSE 3 – med ett utökat tidsfönster. De har visat att det i utvalda fall skulle kunna fungera att behandla upp till 24 timmar efter insjuknandet. Erik Lundström, överläkare vid Neurologen, Akademiska sjukhuset, Uppsala, kommenterar i denna artikel dessa två artiklar och gör en personlig tolkning av vad det kan ha för betydelse för strokevården i Sverige.

  • 247.
    Lundström, E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Karolinska University Hospital, Stockholm, Sweden.
    Isaksson, Eva
    Wester, Per
    Laska, Ann-Charlotte
    Näsman, Per
    Enhancing Recruitment Using Teleconference and Commitment Contract (ERUTECC): study protocol for a randomised, stepped-wedge cluster trial within the EFFECTS trial.2018In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 19, no 1, article id 14Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Many randomised controlled trials (RCTs) fail to meet their recruitment goals in time. Trialists are advised to include study recruitment strategies within their trials. EFFECTS is a Swedish, academic-led RCT of fluoxetine for stroke recovery. The trial's primary objective is to investigate whether 20 mg fluoxetine daily compared with placebo for 6 months after an acute stroke improves the patient's functional outcome. The first patient was included on 20 October 2014 and, as of 31 August 2017, EFFECTS has included 810 of planned 1500 individuals. EFFECTS currently has 32 active centres. The primary objective of the ERUTECC (Enhancing Recruitment Using Teleconference and Commitment Contract) study is to investigate whether a structured teleconference re-visit with the study personnel at the centres, accompanied by a commitment contract, can enhance recruitment by 20% at 60 days post intervention, compared with 60 days pre-intervention, in an ongoing RCT.

    METHODS: ERUTECC is a randomised, stepped-wedge cluster trial embedded in EFFECTS. The plan is to start ERUTECC with a running-in period of September 2017. The first intervention is due in October 2017, and the study will continue for 12 months. We are planning to intervene at all active centres in EFFECTS, except the five top recruiting centres (n = 27). The rationale for not intervening at the top recruiting centres is that we believe they have reached their full potential and the intervention would be too weak for them. The hypothesis of this study is that a structured teleconference re-visit with the study personnel at the centres, accompanied by a commitment contract, can enhance recruitment by 20% 60 days post intervention, compared to 60 days pre-intervention, in an ongoing RCT.

    DISCUSSION: EFFECTS is a large, pragmatic RCT of stroke in Sweden. Results from the embedded ERUTECC study could probably be generalised to high-income Western countries, and is relevant to trial management and could improve trial management in the future. It might also be useful in clinical settings outside the field of stroke.

    TRIAL REGISTRATIONS: The ERUTECC study was registered in the Northern Ireland Hub for Trials Methodology Research Studies Within a Trial repository ( SWAT58 ) on 30 April 2017. ClinicalTrials.gov, ID: NCT02683213 . Retrospectively registered on 2 February 2016.

  • 248.
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Hur ska alla i Sverige få tillgång till trombektomi vid stroke?2019In: Neurologi i Sverige, ISSN 2000-8538, no 2, p. 46-49Article in journal (Other (popular science, discussion, etc.))
  • 249.
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    International comparisons of stroke costs are always limited2010In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 41, no 7, p. e472-e472Article in journal (Refereed)
  • 250.
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Response to Letter by Dobkin2010In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 41, no 7, p. E471-E471Article in journal (Refereed)
2345678 201 - 250 of 465
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf