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  • 151.
    Gustavsson, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Handläggning av Rädda hjärnan patienter på Akademiska sjukhuset: Före och efter införandet av Rädda hjärnan mappen2006Student paper other, 5 credits / 7,5 HE creditsStudent thesis
  • 152.
    Hagglund, H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Strömberg, U.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Axelsson, H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Svenningsson, A.
    Isaksson, C.
    Wahlin, A.
    Andersen, O.
    Johansson, J.
    Press, R.
    Autologous haematopoietic stem cell transplantation: a viable treatment option for chronic inflammatory demyelinating polyneuropathy2013In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 48, no Suppl. 2, p. S336-S336Article in journal (Other academic)
  • 153.
    Halawa, Imad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Acute Symptomatic Seizure: Clinical and Experimental Studies2017Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Epilepsy is defined as a condition with recurrent unprovoked seizures. When seizures are believed to be provoked they fall into another category of situation related seizures, i.e. acute symptomatic seizures (ASS). The definition of ASS is a clinical seizure occurring in close temporal relationship with an acute insult in the central nervous system (CNS), which may be metabolic, toxic, structural, infectious, or inflammatory. The prognosis after unprovoked seizures and ASS differs with regard to risk of seizure recurrence and mortality.

    In the present thesis, we focused on seizures occurring in relation to common dysmetabolic conditions, and subarachnoid hemorrhage (SAH).

    Specifically we wanted to study the occurrence of ASS in patients with different levels of hyponatremia and hypoglycemia. We also conducted an experimental study in mice to explore the relationship between chemically induced status epilepticus (SE) and hyponatremia. Furthermore, seizures in SAH were recorded and related to appearance of development of delayed cerebral ischemia (DCI). In addition we measured neurofilament light (NFL) and tau in the cerebrospinal fluid (CSF).

    We found a gradual increase in risk of seizures with declining sodium levels. Seizures were the only neurologic manifestation of hyponatremia in patients with moderately decreased sodium levels (> 115 mM).

    In study of a large number of patients with hypoglycemia, a notably low risk for seizures was found. Absolut risk for neurological symptoms at glucose < 2.0mM  (95% CI) was 0.25 (0.13-0.41). This is a finding of potentially great clinical relevance, since seizures in the presence of hypoglycemia are often presumed to be acute symptomatic.

    In an animal study of acute hyponatremia on kainic acid (KA) induced status epilepticus (SE) we found that hyponatremic animals displayed an increased frequency of epileptiform activity and had longer duration of seizures. These results support the clinical observations that hyponatremia aggravates SE.

    In the study of patients with SAH we found that ASS is common (36% of all patients) but seizures were not predictive of the development of DCI. Measurement of the CSF biomarker tau at different time points revealed increased tau concentration between days 4 and 10, which may be associated to DCI.

     

     

  • 154.
    Halawa, Imad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University.
    Acute Symptomatic Seizures: Clinical and Experimental Studies2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Epilepsy is defined as a condition with recurrent unprovoked seizures. When seizures are believed to be provoked they fall into another category of situation-related seizures, i.e. acute symptomatic seizures (ASS). The definition of ASS is a clinical seizure occurring in close temporal relationship with an acute insult in the central nervous system (CNS), which may be metabolic, toxic, structural, infectious or inflammatory. The prognosis after unprovoked seizures and ASS differs with regard to risk of seizure recurrence and mortality.

    This thesis focuses on seizures occurring in relation to common dysmetabolic conditions and subarachnoid haemorrhage (SAH). Specifically, the occurrence of ASS in patients with different levels of hyponatraemia and hypoglycaemia was studied. Furthermore an experimental study in rodents was conducted to explore the relationship between chemically induced status epilepticus (SE) and hyponatraemia. In addition, seizures in relation to acute SAH were recorded and related to appearance of development of delayed cerebral ischemia (DCI). Finally, measurement of neurofilament light (NFL) and tau in the cerebrospinal fluid (CSF) was performed.

    In a large number of patients with hyponatremia a gradual increase (2.5 % – 11 %) in risk of seizures with declining sodium levels was noted. Seizures were the only neurologic manifestation of hyponatraemia in patients with moderately decreased sodium levels (> 115 mM).

    In a study of patients with hypoglycaemia, a notably low risk for seizures was found. Absolute risk for neurological symptoms at glucose < 2.0 mM (95% CI) was 0.25 (0.13-0.41). This is a finding of potentially great clinical relevance, since seizures in the presence of hypoglycaemia are often presumed to be acutely symptomatic.

    In the animal study of acute hyponatraemia on kainic acid (KA) induced status epilepticus (SE) the hyponatraemic animals displayed an increased frequency of epileptiform activity and had longer duration of seizures. These results support the clinical observations that hyponatraemia aggravates SE.

    In the study of patients with SAH seizures were frequent (36% of all patients) but did not predict the development of DCI. Measurement of the CSF biomarker tau at different time points revealed increased tau concentration between days 4 and 10, and may be associated with DCI. 

    List of papers
    1. Hyponatremia and risk of seizures: A retrospective cross-sectional study
    Open this publication in new window or tab >>Hyponatremia and risk of seizures: A retrospective cross-sectional study
    2011 (English)In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 52, no 2, p. 410-413Article in journal (Refereed) Published
    Abstract [en]

    This retrospective cross-sectional study was carried out to study the association between different levels of hyponatremia and the occurrence of epileptic seizures in patients without a prior epilepsy diagnosis. We identified from the hospital database, 363 inpatients of a Swedish County hospital who between March 2003 and August 2006 were found to have serum sodium levels < 125 mm. Medical records were reviewed and we identified 11 patients with seizures in conjunction with their hyponatremia. Seizures were the only neurologic manifestation of hyponatremia in patients with serum sodium levels > 115 mm. Of 150 patients reviewed with serum sodium levels of 120-124 mm, one had a seizure. Using 120-124 mm as reference, odds ratios (95% confidence interval) for having seizures at serum sodium levels of 115-119 mm was 3.85 (0.40-37.53), 8.43 (0.859-82.85) at 110-114 mm, and 18.06 (1.96-166.86) at < 110 mm.

    Keywords
    Seizures, Hyponatremia, Serum sodium, Metabolic derangement
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-149037 (URN)10.1111/j.1528-1167.2010.02939.x (DOI)000287239800026 ()21314679 (PubMedID)
    Available from: 2011-03-15 Created: 2011-03-15 Last updated: 2017-12-11
    2. Hypoglycaemia and Risk of Seizures: a Retrospective Cross-Sectional Study
    Open this publication in new window or tab >>Hypoglycaemia and Risk of Seizures: a Retrospective Cross-Sectional Study
    2014 (English)In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 55, p. 231-231Article in journal, Meeting abstract (Other academic) Published
    National Category
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-229373 (URN)000337979300697 ()
    Conference
    11th European Congress on Epileptology, JUN 29-JUL 03, 2014, Stockholm, SWEDEN
    Available from: 2014-08-06 Created: 2014-08-06 Last updated: 2017-12-05Bibliographically approved
    3. Hyponatremia augments kainic-acid induced status epilepticus in the mouse: A model for dysmetabolic status epilepticus
    Open this publication in new window or tab >>Hyponatremia augments kainic-acid induced status epilepticus in the mouse: A model for dysmetabolic status epilepticus
    2013 (English)In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 54, no SI, p. 106-106Article in journal, Meeting abstract (Other academic) Published
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-209225 (URN)000323826600032 ()
    Conference
    4th London-Innsbruck-Colloquium on Status Epilepticus, APR 04-06, 2013, Salzburg, AUSTRIA
    Available from: 2013-10-15 Created: 2013-10-15 Last updated: 2017-12-06Bibliographically approved
    4. Epileptic seizures and CSF concentrations of neurofilament light and tau proteins in patients with subarachnoid hemorrhage.
    Open this publication in new window or tab >>Epileptic seizures and CSF concentrations of neurofilament light and tau proteins in patients with subarachnoid hemorrhage.
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-314519 (URN)
    Available from: 2017-02-03 Created: 2017-02-02 Last updated: 2017-02-06
  • 155.
    Halawa, Imad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Andersson, Tomas
    Tomson, Torbjörn
    Hyponatremia and risk of seizures: A retrospective cross-sectional study2011In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 52, no 2, p. 410-413Article in journal (Refereed)
    Abstract [en]

    This retrospective cross-sectional study was carried out to study the association between different levels of hyponatremia and the occurrence of epileptic seizures in patients without a prior epilepsy diagnosis. We identified from the hospital database, 363 inpatients of a Swedish County hospital who between March 2003 and August 2006 were found to have serum sodium levels < 125 mm. Medical records were reviewed and we identified 11 patients with seizures in conjunction with their hyponatremia. Seizures were the only neurologic manifestation of hyponatremia in patients with serum sodium levels > 115 mm. Of 150 patients reviewed with serum sodium levels of 120-124 mm, one had a seizure. Using 120-124 mm as reference, odds ratios (95% confidence interval) for having seizures at serum sodium levels of 115-119 mm was 3.85 (0.40-37.53), 8.43 (0.859-82.85) at 110-114 mm, and 18.06 (1.96-166.86) at < 110 mm.

  • 156.
    Halawa, Imad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Vlachogiannis, Pavlos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Amandusson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Elf, Kristin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Zetterberg, H.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden.;UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Seizures, CSF neurofilament light and tau in patients with subarachnoid haemorrhage2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 137, no 2, p. 199-203Article in journal (Refereed)
    Abstract [en]

    Objectives

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

    Methods

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

    Results

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

    Conclusion

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

  • 157.
    Halawa, Imad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zelano, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Hypoglycaemia and Risk of Seizures: a Retrospective Cross-Sectional Study2014In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 55, p. 231-231Article in journal (Other academic)
  • 158.
    Halawa, Imad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zelano, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Hypoglycemia and risk of seizures: A retrospective cross-sectional study2015In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 25, p. 147-149Article in journal (Refereed)
    Abstract [en]

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

  • 159.
    Hallberg, Pär
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Smedje, Hans
    Division of Child and Adolescent Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kohnke, Hugo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Daniilidou, Makrina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Öhman, Inger
    Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden.
    Yue, Qun-Ying
    Medical Products Agency, Uppsala, Sweden.
    Cavalli, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wadelius, Claes
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Magnusson, Patrik K. E.
    Swedish Twin Registry, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pandemrix-induced narcolepsy is associated with genes related to immunity and neuronal survival2019In: EBioMedicine, E-ISSN 2352-3964, Vol. 40, p. 595-604Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The incidence of narcolepsy rose sharply after the swine influenza A (H1N1) vaccination campaign with Pandemrix. Narcolepsy is an immune-related disorder with excessive daytime sleepiness. The most frequent form is strongly associated with HLA-DQB1*06:02, but only a minority of carriers develop narcolepsy. We aimed to identify genetic markers that predispose to Pandemrix-induced narcolepsy.

    METHODS: We tested for genome-wide and candidate gene associations in 42 narcolepsy cases and 4981 controls. Genotyping was performed on Illumina arrays, HLA alleles were imputed using SNP2HLA, and single nucleotide polymorphisms were imputed using the haplotype reference consortium panel. The genome-wide significance threshold was p < 5 × 10-8, and the nominal threshold was p < 0.05. Results were replicated in 32 cases and 7125 controls. Chromatin data was used for functional annotation.

    FINDINGS: Carrying HLA-DQB1*06:02 was significantly associated with narcolepsy, odds ratio (OR) 39.4 [95% confidence interval (CI) 11.3, 137], p = 7.9 × 10-9. After adjustment for HLA, GDNF-AS1 (rs62360233) was significantly associated, OR = 8.7 [95% CI 4.2, 17.5], p = 2.6 × 10-9, and this was replicated, OR = 3.4 [95% CI 1.2-9.6], p = 0.022. Functional analysis revealed variants in high LD with rs62360233 that might explain the detected association. The candidate immune-gene locus TRAJ (rs1154155) was nominally associated in both the discovery and replication cohorts, meta-analysis OR = 2.0 [95% CI 1.4, 2.8], p = 0.0002.

    INTERPRETATION: We found a novel association between Pandemrix-induced narcolepsy and the non-coding RNA gene GDNF-AS1, which has been shown to regulate expression of the essential neurotrophic factor GDNF. Changes in regulation of GDNF have been associated with neurodegenerative diseases. This finding may increase the understanding of disease mechanisms underlying narcolepsy. Associations between Pandemrix-induced narcolepsy and immune-related genes were replicated.

  • 160. Hallböök, Tove
    et al.
    Azakacs, Attila
    Bialek, Fatima
    Feltelius, Nils
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Malmgren, Kristina
    Narkolepsi – ovanlig sjukdomsom fått ökad uppmärksamhet: Pandemrixvaccination ledde till fler insjuknanden bland barn och ungdomar2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 41, p. 1770-1773Article in journal (Refereed)
    Abstract [sv]

    Narkolepsi är en ovanlig sjukdom där symtomen beror på störd reglering av sömn och vakenhet. Kardinalsymtom är uttalad dagsömnighet, kataplexiattacker och nattlig dyssomni. 

    Etiologin anses betingad av en autoimmun process hos predisponerade individer, där omgivningsfaktorer är av betydelse för att utlösa sjukdomen.

    Pandemrixvaccinationen ledde till ökat insjuknande hos barn och ungdomar och en viss ökning hos unga vuxna.

    Behandlingen utgör en kombination av läkemedel med effekt på kardinalsymtomen och livsstilsråd, där teamomhändertagande är viktigt.

    Svenska narkolepsiregistret ger möjlighet att följa sjukdomsförlopp och behandling, vilket är viktigt inte minst eftersom dokumentationen av de läkemedel som används är begränsad.

  • 161.
    Hanrieder, Jörg
    et al.
    Department of Chemical and Biological Engineering, Analytical Chemistry, Chalmers University of Technology, Gothenburg, Sweden;.
    Ekegren, Titti
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Andersson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    MALDI Imaging of Post Mortem Human Spinal Cord in Amyotrophic Lateral Sclerosis2013In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 124, no 5, p. 695-707Article in journal (Refereed)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease of the central nervous system that is characterized by motor neuron degeneration in the brain stem and the spinal cord. Matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is an emerging powerful technique that allows for spatially resolved, comprehensive and specific characterization of molecular species in situ. In this study we report for the first time, MALDI imaging-based spatial protein profiling and relative quantification of post mortem human spinal cord samples obtained from ALS patients and controls. In normal spinal cord, protein distribution patterns were well in line with histological features. For example, thymosin beta 4, ubiquitin, histone proteins, acyl CoA binding protein, and macrophage inhibitory factor were predominantly localized to the grey matter. Furthermore, unsupervised statistics revealed a significant reduction of two protein species in ALS grey matter. One of these proteins (m/z 8451) corresponds to an endogenous truncated form of ubiquitin (Ubc 1-76), with both C-terminal glycine residues removed (Ubc-T/Ubc 1-74). This region-specific ubiquitin processing suggests a disease-related change in protease activity. These results highlight the importance of MALDI IMS as a versatile approach to elucidate molecular mechanisms of neurodegenerative diseases.

  • 162.
    Hansen, Julia
    et al.
    Univ Gothenburg, Dept Neurol, Sahlgrenska Univ Hosp, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden..
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zelano, Johan
    Univ Gothenburg, Dept Neurol, Sahlgrenska Univ Hosp, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden..
    Cause of death in patients with poststroke epilepsy: Results from a nationwide cohort study2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, article id e0174659Article in journal (Refereed)
    Abstract [en]

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

  • 163. Hedberg, C.
    et al.
    Ohlsson, M.
    Bradvik, B.
    Lindberg, C.
    Tajsharghi, H.
    Danielsson, O.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Udd, B.
    Martinsson, T.
    Oldfors, A.
    Hereditary myopathy with early respiratory failure associated with a mutation in A-band titin2012In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 22, no 9-10, p. 873-873Article in journal (Other academic)
    Abstract [en]

    Hereditary myopathy with early respiratory failure (HMERF) and extensive myofibrillar lesions have been described in sporadic and familial cases and linked to various chromosomal regions. We describe the clinical manifestations, muscle histopathology and genetics in eight individuals from three apparently unrelated families with clinical and pathological features of HMERF. All patients had muscle weakness in the pelvic girdle, neck flexors, respiratory and trunk muscles, and the majority had prominent calf hypertrophy. Examination of pulmonary function showed decreased vital capacity. No signs of cardiac muscle involvement were found. Muscle histopathological features included marked muscle fibre size variation, fibre splitting, numerous internal nuclei and fatty infiltration. Frequent groups of fibres showed eosinophilic inclusions and deposits. At the ultrastructural level there were extensive myofibrillar lesions with marked Z-disc alterations. Whole exome sequencing in four individuals from one family revealed a missense mutation, g.274375, T>C; p.Cys30071Arg, in the titin gene, TTN. The mutation, which changes a highly conserved residue in the myosin binding A-band titin, was demonstrated to segregate with the disease in all three families. High density single nucleotide polymorphism arrays covering the entire genome demonstrated sharing of a 699 Mb haplotype, located in chromosome region 2q31 including TTN, indicating common ancestry of this novel and first disease-causing mutation in A-band titin associated with HMERF.

  • 164. Hedberg, Carola
    et al.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Dahlbom, Kathe
    Oldfors, Anders
    Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain2014In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 137, no 4, p. e270-Article in journal (Refereed)
  • 165. Hedberg, Carola
    et al.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kuhl, Angelika
    Jenne, Dieter
    Oldfors, Anders
    Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7 is caused by a DES mutation2012In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 20, no 9, p. 984-985Article in journal (Refereed)
    Abstract [en]

    Using exome sequencing we searched for the genetic cause of autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy (ARVC) in a Swedish family. A heterozygous C-to-T transition, c.1255C>T, p.Pro419Ser in the desmin gene on chromosome 2q35, was identified. Previous studies had demonstrated linkage to chromosome 10q22.3, but no causative mutation had been found in that region. Sanger sequencing of DNA from 17 family members confirmed the heterozygous c.1255C>T desmin mutation in seven out of ten family members that had been classified as affected in the previous study. Our new results demonstrate the usefulness of next-generation sequencing, and the diagnostic difficulties with some forms of dominantly inherited muscle diseases as they can display a wide clinical and morphological variability even within a given family.

  • 166. Hedberg, Carola
    et al.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kuhl, Angelika
    Jenne, Dieter
    Oldfors, Anders
    Functional characterization of desmin mutant p.P419S Reply2013In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 21, no 6, p. 590-590Article in journal (Refereed)
  • 167.
    Hedborg, Kerstin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Muhr, Carin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The influence of multimodal behavioral treatment on theconsumption of acute migraine drugs: a randomized, controlled study2012In: Cephalalgia, ISSN 0333-1024, E-ISSN 1468-2982, Vol. 32, no 4, p. 297-307Article in journal (Other academic)
    Abstract [en]

    Objectives: To characterize overall drug use in migraine in conjunction with multimodal behavioral treatment.

    Methods: 76 adults reporting at least two monthly migraine attacks underwent a randomized, controlled 24-week multimodal behavioral treatment intervention. Migraine drugs and symptoms were registered in an Internet-based diary.

    Results: During 4256 days of baseline registration, 859 drug doses were taken during 655 of the 856 days with migraine headache. Triptans and analgesics constituted 56.7 and 38.3 percent of all doses with efficacy ratios of 0.41, and 0.20, respectively. Men displayed significantly lower drug efficacy (p = 0.001) and used triptans significantly less (p < 0.001) and analgesics significantly more (p < 0.001) than women did. At the end of multimodal behavioral treatment, total drug consumption decreased by 22 percent (p = 0.021), corresponding to 27 percent fewer days with migraine headache. Drug efficacy increased during multimodal behavioral treatment from 0.30 to 0.52 (p < 0.001), mainly explained by an increased proportion of mild attacks which also was the attack category which displayed the largest increase in drug efficacy.

    Conclusions: Triptans were the most used and efficient drugs. Multimodal behavioral treatment led to decreased and more efficient drug consumption. Men used triptans less frequently.

  • 168.
    Herman, Stephanie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Emami Khoonsari, Payam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Tolf, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Steinmetz, Julia
    Zetterberg, Henrik
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Jakobsson, Per-Johan
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Spjuth, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Integration of magnetic resonance imaging and protein and metabolite CSF measurements to enable early diagnosis of secondary progressive multiple sclerosis.2018In: Theranostics, ISSN 1838-7640, E-ISSN 1838-7640, Vol. 8, no 16, p. 4477-4490Article in journal (Refereed)
    Abstract [en]

    Molecular networks in neurological diseases are complex. Despite this fact, contemporary biomarkers are in most cases interpreted in isolation, leading to a significant loss of information and power. We present an analytical approach to scrutinize and combine information from biomarkers originating from multiple sources with the aim of discovering a condensed set of biomarkers that in combination could distinguish the progressive degenerative phenotype of multiple sclerosis (SPMS) from the relapsing-remitting phenotype (RRMS).

    Methods: Clinical and magnetic resonance imaging (MRI) data were integrated with data from protein and metabolite measurements of cerebrospinal fluid, and a method was developed to sift through all the variables to establish a small set of highly informative measurements. This prospective study included 16 SPMS patients, 30 RRMS patients and 10 controls. Protein concentrations were quantitated with multiplexed fluorescent bead-based immunoassays and ELISA. The metabolome was recorded using liquid chromatography-mass spectrometry. Clinical follow-up data of the SPMS patients were used to assess disease progression and development of disability.

    Results: Eleven variables were in combination able to distinguish SPMS from RRMS patients with high confidence superior to any single measurement. The identified variables consisted of three MRI variables: the size of the spinal cord and the third ventricle and the total number of T1 hypointense lesions; six proteins: galectin-9, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor alpha (TGF-α), tumor necrosis factor alpha (TNF-α), soluble CD40L (sCD40L) and platelet-derived growth factor AA (PDGF-AA); and two metabolites: 20β-dihydrocortisol (20β-DHF) and indolepyruvate. The proteins myelin basic protein (MBP) and macrophage-derived chemokine (MDC), as well as the metabolites 20β-DHF and 5,6-dihydroxyprostaglandin F1a (5,6-DH-PGF1), were identified as potential biomarkers of disability progression.

    Conclusion: Our study demonstrates, in a limited but well-defined and data-rich cohort, the importance and value of combining multiple biomarkers to aid diagnostics and track disease progression.

  • 169.
    Herman, Stephanie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Niemelä, Valter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Emami Khoonsari, Payam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Spjuth, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington's disease subjects2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4129Article in journal (Refereed)
    Abstract [en]

    Huntington's disease (HD) is a severe neurological disease leading to psychiatric symptoms, motor impairment and cognitive decline. The disease is caused by a CAG expansion in the huntingtin (HTT) gene, but how this translates into the clinical phenotype of HD remains elusive. Using liquid chromatography mass spectrometry, we analyzed the metabolome of cerebrospinal fluid (CSF) from premanifest and manifest HD subjects as well as control subjects. Inter-group differences revealed that the tyrosine metabolism, including tyrosine, thyroxine, L-DOPA and dopamine, was significantly altered in manifest compared with premanifest HD. These metabolites demonstrated moderate to strong associations to measures of disease severity and symptoms. Thyroxine and dopamine also correlated with the five year risk of onset in premanifest HD subjects. The phenylalanine and the purine metabolisms were also significantly altered, but associated less to disease severity. Decreased levels of lumichrome were commonly found in mutated HTT carriers and the levels correlated with the five year risk of disease onset in premanifest carriers. These biochemical findings demonstrates that the CSF metabolome can be used to characterize molecular pathogenesis occurring in HD, which may be essential for future development of novel HD therapies.

  • 170.
    Herman, Stephanie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Spjuth, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing-Remitting Multiple Sclerosis2019In: Cells, ISSN 2073-4409, Vol. 8, no 2, article id 84Article in journal (Refereed)
    Abstract [en]

    To better understand the pathophysiological differences between secondary progressive multiple sclerosis (SPMS) and relapsing-remitting multiple sclerosis (RRMS), and to identify potential biomarkers of disease progression, we applied high-resolution mass spectrometry (HRMS) to investigate the metabolome of cerebrospinal fluid (CSF). The biochemical differences were determined using partial least squares discriminant analysis (PLS-DA) and connected to biochemical pathways as well as associated to clinical and radiological measures. Tryptophan metabolism was significantly altered, with perturbed levels of kynurenate, 5-hydroxytryptophan, 5-hydroxyindoleacetate, and N-acetylserotonin in SPMS patients compared with RRMS and controls. SPMS patients had altered kynurenine compared with RRMS patients, and altered indole-3-acetate compared with controls. Regarding the pyrimidine metabolism, SPMS patients had altered levels of uridine and deoxyuridine compared with RRMS and controls, and altered thymine and glutamine compared with RRMS patients. Metabolites from the pyrimidine metabolism were significantly associated with disability, disease activity and brain atrophy, making them of particular interest for understanding the disease mechanisms and as markers of disease progression. Overall, these findings are of importance for the characterization of the molecular pathogenesis of SPMS and support the hypothesis that the CSF metabolome may be used to explore changes that occur in the transition between the RRMS and SPMS pathologies.

  • 171. Holmen, C.
    et al.
    Piehl, F.
    Hillert, J.
    Nilsson, P.
    Dahle, C.
    Feltelius, N.
    Svenningsson, A.
    Lycke, J.
    Fagius, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Valentin, F.
    Martin, C.
    Olsson, T.
    The 'Immunomodulation and Multiple Sclerosis Epidemiology' (IMSE) study: a Swedish nationwide pharmaco-epidemiological and genetic study focused on long-term safety and efficacy of natalizumab (Tysabri)2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no S1, p. 751-751Article in journal (Other academic)
  • 172. Hubers, Anna A M
    et al.
    van Duijn, Erik
    Roos, Raymund A C
    Craufurd, David
    Rickards, Hugh
    Bernhard Landwehrmeyer, G
    van der Mast, Rose C
    Giltay, Erik J
    Suicidal ideation in a European Huntington's disease population.2013In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 151, no 1, p. 248-58, article id S0165-0327(13)00472-2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD.

    METHODS: The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's Disease Network. Of the 1937 participants without suicidal ideation at baseline, 945 had one or more follow-up measurements. Participants were assessed for suicidal ideation by the behavioural subscale of the Unified Huntington's Disease Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using logistic regression analysis and predictors were analyzed using Cox regression analysis.

    RESULTS: At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9-1.0), anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5-3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood (OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%. Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI: 1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were independent predictors of incident suicidal ideation, whereas a previous suicide attempt was not predictive.

    LIMITATIONS: As suicidal ideation was assessed by only one item, and participants were a selection of all HD mutation carriers, the prevalence of suicidal ideation was likely underestimated.

    CONCLUSIONS: Suicidal ideation in HD frequently occurs. Assessment of suicidal ideation is a priority in mutation carriers with a depressed mood and in those using benzodiazepines.

  • 173. Hägerstrand, Daniel
    et al.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Eriksson, Anna
    Sigurdardottir, Sunna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Olofsson, Tommie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Hartman, Magdalena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Nistér, Monica
    Kalimo, Hannu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Östman, Arne
    Gene expression analyses of grade II gliomas and identification of rPTPbeta/ as a candidate oligodendroglioma marker2008In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 10, no 1, p. 2-9Article in journal (Refereed)
    Abstract [en]

    Grade 11 gliomas are morphologically and clinically heterogeneous tumors for which histopathological typing remains the major tool for clinical classification. To what extent the major histological subtypes-astrocytomas, oligodendrogliomas, and oligoastrocytomas-constitute true biological entities is largely unresolved. Furthermore, morphological classification is often ambiguous and would be facilitated by specific subtype markers. In this study, 23 grade II gliomas were expression-profiled and subjected to hierarchical clustering. All six oligodendrogliomas were grouped together in one of two major clusters; a significant correlation was thus observed between gene expression and histopathological subtype. Supervised analyses were performed to identify genes differentiating oligodendrogliomas from other grade II tumors. In a leave-one-out test using 10 features for classification, 20 out of 23 tumors were correctly classified. Among the most differentially expressed genes was rPT beta/zeta. The expression of the rPTP beta/zeta protein in oligodendrogliomas and astrocytomas was further validated by immunohistochemistry in an independent set of tumors. All 11 oligodendrogliomas of this set displayed strong staining. In contrast, neoplastic astrocytes were mostly negative for rPTP beta/zeta staining. In summary, this study demonstrates a correlation between gene expression pattern and histological subtype in grade 11 gliomas. Furthermore, the results from the immunohistochemical analyses of rPTP beta/zeta expression should prompt further evaluation of this protein as a novel oligodendroglioma marker.

  • 174.
    Ilias, Thomas
    et al.
    Dalarna Univ, S-79131 Falun, Sweden..
    Filip, Bergquist
    Gothenburg Univ, S-40530 Gothenburg, Sweden..
    Radu, Constantinescu
    Gothenburg Univ, S-40530 Gothenburg, Sweden..
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Senek, Marina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Mevludin, Memedi
    Dalarna Univ, S-70281 Orebro, Sweden.;Orebro Univ, S-70281 Orebro, Sweden..
    Using measurements from wearable sensors for automatic scoring of Parkinson's disease motor states: results from 7 patients2017In: 2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), IEEE , 2017, p. 131-134Conference paper (Refereed)
    Abstract [en]

    The objective of this study was to investigate the validity of an objective gait measure for assessment of different motor states of advanced Parkinson's disease (PD) patients. Seven PD patients performed a gait task up to 15 times while wearing sensors on their upper and lower limbs. Each task was performed at specific points during a test day, following a single dose of levodopa-carbidopa. At the time of the tasks the patients were video recorded and three movement disorder experts rated their motor function on three clinical scales: a treatment response scale (TRS) that ranged from -3 (very bradykinetic) to 0 (ON) to +3 (very dyskinetic), a dyskinesia score that ranged from 0 (no dyskinesia) to 4 (extreme dyskinesia), and a bradykinesia score that ranged from 0 (no bradykinesia) to 4 (extreme bradykinesia). Raw accelerometer and gyroscope data of the sensors were processed and analyzed with time series analysis methods to extract features. The utilized features quantified separate limb movements as well as movement symmetries between the limbs. The features were processed with principal component analysis and the components were used as predictors for separate support vector machine (SVM) models for each of the three scales. The performance of each model was evaluated in a leave-one-patient out setting where the observations of a single patient were used as the testing set and the observations of the other 6 patients as the training set. Root mean square error (RMSE) and correlation coefficients for the predictions showed a good ability of the models to map the sensor data into the rating scales. There were strong correlations between the SVM models and the mean ratings of TRS (0.79; RMSE=0.70), bradykinesia score (0.79; RMSE=0.47), and bradykinesia score (0.78; RMSE=0.46). The results presented in this paper indicate that the use of wearable sensors when performing gait tasks can generate measurements that have a good correlation to subjective expert assessments.

  • 175.
    Imrell, K.
    et al.
    Karolinska Inst, Stockholm, Sweden..
    Masterman, T.
    Karolinska Inst, Stockholm, Sweden..
    Brynedal, B.
    Karolinska Inst, Stockholm, Sweden..
    Lima, I.
    Karolinska Inst, Stockholm, Sweden..
    Hillert, J.
    Karolinska Inst, Stockholm, Sweden..
    Kockum, I.
    Karolinska Inst, Stockholm, Sweden..
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Genetic load in eleven distantly related individuals from an MS high risk area2015In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, p. 435-436Article in journal (Other academic)
  • 176.
    Ingelsson, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nilsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Konformationsförändrade proteiner orsakar neurodegenerativa sjukdomar2005In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, no 47, p. 3542-3551Article in journal (Refereed)
    Abstract [en]

    Brain aggregates of conformationally altered proteins are key features of neurodegeneration and are believed to directly cause or contribute to disease development. Mechanisms underlying the dysregulation of proteins in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and other neurodegenerative disorders are now being characterized, due to the discovery of genes causing rare disease forms. As of today, only symptomatic pharmacotherapies are available, but new insights into the underlying molecular mechanisms are providing strategies to prevent or even cure these devastating disorders.

  • 177.
    Innocenti, C.
    et al.
    Careggi Univ Hosp, Hematol, Florence, Italy; Northwestern Hosp, Dept Immunotherapy & Autoimmune Dis, Chicago, IL USA.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Burns, C.
    Northwestern Univ, Dept Immunotherapy & Autoimmune Dis, Chicago, IL USA.
    Burt, R.
    Northwestern Hosp, Dept Immunotherapy & Autoimmune Dis, Chicago, IL USA.
    Inflammatory immune response after autologous transplantation in neurologic diseases2017In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 52, no Supplement: 1, p. S420-S420Article in journal (Other academic)
  • 178.
    Isacson, D
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Bingefors, K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Kristiansen, I S
    Nyholm, D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Fluctuating functions related to quality of life in advanced Parkinson disease: effects of duodenal levodopa infusion2008In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 118, no 6, p. 379-86Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess fluctuations in quality of life (QoL) and motor performance in patients with advanced Parkinson disease (PD) treated with continuous daytime duodenal levodopa/carbidopa infusion or conventional therapy. METHODS: Of 18 patients completing a 6-week trial (DIREQT), 12 were followed for up to 6 months and assessed using electronic diaries and the PD Questionnaire-39 (PDQ-39). RESULTS: During the trial and follow-up, major diurnal fluctuations were observed, especially for hyperkinesia, 'off' time, ability to walk and depression. Duodenal infusion was associated with significantly more favourable outcomes compared with conventional treatment for satisfaction with overall functioning, 'off' time and ability to walk, with improved outcomes with PDQ-39. CONCLUSIONS: Relative to conventional treatment, infusion therapy may stabilize and significantly improve motor function and patient's QoL. The potential for daily fluctuation in PD symptoms means single measures of treatment effectiveness can result in bias in effect estimates and hence repeated measures are recommended.

  • 179.
    Jakobsson Larsson, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    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.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nygren, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Coping strategies among patients with newly diagnosed amyotrophic lateral sclerosis2014In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 23, no 21-22, p. 3148-3155Article in journal (Refereed)
    Abstract [en]

    AIMS AND OBJECTIVES: To prospectively identify different coping strategies among newly diagnosed amyotrophic lateral sclerosis patients and whether they change over time and to determine whether physical function, psychological well-being, age and gender correlated with the use of different coping strategies.

    BACKGROUND: Amyotrophic lateral sclerosis is a fatal disease with impact on both physical function and psychological well-being. Different coping strategies are used to manage symptoms and disease progression, but knowledge about coping in newly diagnosed amyotrophic lateral sclerosis patients is scarce.

    DESIGN: This was a prospective study with a longitudinal and descriptive design.

    METHODS: A total of 33 patients were included and evaluation was made at two time points, one to three months and six months after diagnosis. Patients were asked to complete the Motor Neuron Disease Coping Scale and the Hospital Anxiety and Depression Scale. Physical function was estimated using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale.

    RESULTS: The most commonly used strategies were support and independence. Avoidance/venting and information seeking were seldom used at both time points. The use of information seeking decreased between the two time points. Men did not differ from women, but patients ≤64 years used positive action more often than older patients. Amyotrophic Lateral Sclerosis Functional Rating Scale was positively correlated with positive action at time point 1, but not at time point 2. Patients' psychological well-being was correlated with the use of different coping strategies.

    CONCLUSIONS: Support and independence were the most used coping strategies, and the use of different strategies changed over time. Psychological well-being was correlated with different coping strategies in newly diagnosed amyotrophic lateral sclerosis patients.

    RELEVANCE TO CLINICAL PRACTICE: The knowledge about coping strategies in early stage of the disease may help the nurses to improve and develop the care and support for these patients.

  • 180.
    Jakobsson Larsson, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    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.
    Coping with amyotrophic lateral sclerosis; from diagnosis and during disease progression2016In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 361, p. 235-242Article in journal (Refereed)
    Abstract [en]

    To evaluate coping strategies among patients with Amyotrophic lateral sclerosis starting with diagnosis and during the disease progression, as well as investigate changes and correlations between coping strategies, emotional well-being and physical function. A total of 36 patients participated in the study. The patients filled out the Hospital Anxiety and Depression Scale and the Motor Neuron Disease Coping Scale. Physical function was measured using the revised ALS functional rating scale. Data were collected regularly from diagnosis and over a two years period. As a way to cope with the disease patients relied on both problem focused and emotional focused strategies. The use of coping strategies remained stable. Both physical disabilities and emotional well-being was related to some coping strategies, with some variation during the disease progression. Moreover, some coping strategies were related to symptoms of anxiety and depression. Irrespective of whether the coping strategies affect the emotional well-being or vice versa, the results show the importance of early and continuous evaluation of coping and emotional well-being to ease the emotional distress and provide support to the patient so that he/she can cope with the disease during the disease progression.

  • 181.
    Jakobsson Larsson, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Ozanne, A G
    Neurology, Clinical Neuroscience, Sahlgrenska Universitetssjukhus, Göteborg, Sweden.
    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.
    A prospective study of quality of life in amyotrophic lateral sclerosis patients2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, no 6, p. 631-638Article in journal (Refereed)
    Abstract [en]

    OBJECTS: The aim of this prospective and longitudinal study was to describe individual quality of life in patients with amyotrophic lateral sclerosis (ALS) and its correlations with physical function and emotional well-being from diagnosis and over time.

    MATERIALS AND METHODS: Thirty-six patients were included in the study. Individual quality of life was measured with the Schedule of Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), illness severity was assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS FRS-R), and emotional distress was measured using the Hospital Anxiety and Depression Scale (HADS). Data were collected from diagnosis and thereafter, every six months for a period of two years. Twelve patients completed the 24-month follow-up.

    RESULTS: Family, friends and own physical health were important for overall quality of life, from diagnosis and during the disease progression. Most patients had good quality of life, which remained stable, despite changed physical functions. Several patients scored above the cut-off score for doubtful and clinical anxiety and depression early on after diagnosis, and there was a significant decrease in anxiety over time. Soon after diagnosis, there was a correlation between depression and quality of life.

    CONCLUSION: The family, social relations and own physical health are important for overall quality of life in patients with ALS. Thus, supporting the family and facilitating so that patients can continue to stay in contact with friends are important aspects during the disease. Conducting an early screening for depression can be important for preventing decreased quality of life.

  • 182.
    Jansson, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Axelson, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Stochastic anomaly detection in eye-tracking data for quantification of motor symptoms in Parkinson's disease2015In: Signal and Image Analysis for Biomedical and Life Sciences, Springer, 2015, p. 63-82Chapter in book (Refereed)
    Abstract [en]

    Two methods for distinguishing between healthy controls and patients diagnosed with Parkinson's disease by means of recorded smooth pursuit eye movements are presented and evaluated. Both methods are based on the principles of stochastic anomaly detection and make use of orthogonal series approximation for probability distribution estimation. The first method relies on the identification of a Wiener model of the smooth pursuit system and attempts to find statistically significant differences between the estimated parameters in healthy controls and patients with Parkinson's disease. The second method applies the same statistical method to distinguish between the gaze trajectories of healthy and Parkinson subjects tracking visual stimuli. Both methods show promising results, where healthy controls and patients with Parkinson's disease are effectively separated in terms of the considered metric. The results are preliminary because of the small number of participating test subjects, but they are indicative of the potential of the presented methods as diagnosing or staging tools for Parkinson's disease.

  • 183.
    Jansson, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Axelson, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Stochastic anomaly detection in eye-tracking data for quantification of motor symptoms in Parkinson's disease2013In: International Symposium on Computational Models for Life Sciences: CMLS 2013, Melville, NY: American Institute of Physics (AIP), 2013, p. 98-107Conference paper (Refereed)
    Abstract [en]

    Two methods for distinguishing between healthy controls and patients diagnosed with Parkinson's disease by means of recorded smooth pursuit eye movements are presented and evaluated. Both methods are based on the principles of stochastic anomaly detection and make use of orthogonal series approximation for probability distribution estimation. The first method relies on the identification of a Wiener-type model of the smooth pursuit system and attempts to find statistically significant differences between the estimated parameters in healthy controls and patientts with Parkinson's disease. The second method applies the same statistical method to distinguish between the gaze trajectories of healthy and Parkinson subjects attempting to track visual stimuli. Both methods show promising results, where healthy controls and patients with Parkinson's disease are effectively separated in terms of the considered metric. The results are preliminary because of the small number of participating test subjects, but they are indicative of the potential of the presented methods as diagnosing or staging tools for Parkinson's disease.

  • 184. Jensen, Susanne Sartov
    et al.
    Naesh, Ole
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Parkinsons sjukdom: en utmaning för anestesiologen.2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 23, p. 1552-1555Article in journal (Refereed)
    Abstract [sv]

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

    Andelen äldre ökar i populationen, och härav följer att ett ökande antal patienter med Parkinsons sjukdom kommer att genomgå operation och anestesi.

     Parkinsonpatienter behandlas med farmaka som potentiellt interagerar med perioperativt använda läkemedel.

     Abrupt perioperativ utsättning av antiparkinsonläkemedel ökar risken för försämring av grundsjukdomen och för neurologiska komplikationer ("malingt syndrom").

     Parkinsonpatienter har inte sällan autonom dysfunktion, som kan komplicera det perioperativa förloppet.

     Andra sjukdomar är vanliga i denna patientgrupp.

     Det är viktigt att planera det perioperativa förloppet noggrant, likaså att fortsätta med antiparkinsonmedicinering under hela det perioperativa förloppet.

     Det finns idag ingen evidens för att en viss anestesimetod är att föredra framför en annan för denna patientgrupp. Regimen måste individualiseras och hänsyn tas till patientens grundmedicinering, grad av parkinsonkomplikationer och ingreppets natur.

     

  • 185.
    Jin, Zhe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Mendu, Suresh Kumar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    GABA is an effective immunomodulatory molecule2013In: Amino Acids, ISSN 0939-4451, E-ISSN 1438-2199, Vol. 45, no 1, p. 87-94Article in journal (Refereed)
    Abstract [en]

    In recent years, it has become clear that there is an extensive cross-talk between the nervous and the immune system. Somewhat surprisingly, the immune cells themselves do express components of the neuronal neurotransmitters systems. What role the neurotransmitters, their ion channels, receptors and transporters have in immune function and regulation is an emerging field of study. Several recent studies have shown that the immune system is capable of synthesizing and releasing the classical neurotransmitter GABA (γ-aminobutyric acid). GABA has a number of effects on the immune cells such as activation or suppression of cytokine secretion, modification of cell proliferation and GABA can even affect migration of the cells. The immune cells encounter GABA when released by the immune cells themselves or when the immune cells enter the brain. In addition, GABA can also be found in tissues like the lymph nodes, the islets of Langerhans and GABA is in high enough concentration in blood to activate, e.g., GABA-A channels. GABA appears to have a role in autoimmune diseases like multiple sclerosis, type 1 diabetes, and rheumatoid arthritis and may modulate the immune response to infections. In the near future, it will be important to work out what specific effects GABA has on the function of the different types of immune cells and determine the underlying mechanisms. In this review, we discuss some of the recent findings revealing the role of GABA as an immunomodulator.

  • 186.
    Johansson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Search for Biomarkers in ALS and Parkinson's Disease: Positron Emission Tomography and Cerebrospinal Fluid Studies2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    New biomarkers are needed to improve knowledge about pathophysiology, in order to provide earlier correct diagnosis and to follow disease progression of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). The aim of this thesis was to find new biomarkers for these diseases.

    First, increased serum levels and unchanged levels in postmortal spinal cord of vascular endothelial growth factor (VEGF) were demonstrated. VEGF was not detected in cerebrospinal fluid (CSF) in ALS. Second, increased levels of fibroblast growth factor 2 were found in the CSF and serum of ALS patients. Both studies used enzyme-linked immunoassays. Third, a proteomics method for CSF analysis was explored, based on tryptic digestion and subsequent separation and detection of the peptides by on-line liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry. ALS-specific patterns were observed. Four out of five samples were correctly assigned, but no single protein biomarker could be identified. Fourth, [11C](L)-deprenyl-D2 (DED) positron emission tomography (PET) demonstrated increased retention in the pons and white matter in ALS. DED binds to monoamino oxidase B, which in the brain is primarily located in astrocytes. Thus evidence was provided that astrocytosis may be detected in vivo in ALS.

    Fifth, normal [11C]-PIB binding in five nondemented patients with PD was reported, in contrast to previous findings of increased retention in Alzheimer's disease reflecting amyloid aggregation. Finally, the combined use of fluorodeoxyglucose and L-[β 11C]-DOPA PET for the differential diagnosis of parkinsonian syndromes was evaluated. PET provided support for the clinical diagnosis in 62 out of 75 patients, and served to exclude suspected diagnoses in another five patients.

    List of papers
    1. VEGF is increased in serum but not in spinal cord from patients with amyotrophic lateral sclerosis
    Open this publication in new window or tab >>VEGF is increased in serum but not in spinal cord from patients with amyotrophic lateral sclerosis
    2002 In: NeuroReport, Vol. 13, no 17, p. 2199-2201Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92661 (URN)
    Available from: 2005-03-17 Created: 2005-03-17Bibliographically approved
    2. Increased serum and cerebrospinal fluid FGF-2 levels in amyotrophic lateral sclerosis
    Open this publication in new window or tab >>Increased serum and cerebrospinal fluid FGF-2 levels in amyotrophic lateral sclerosis
    Show others...
    2003 (English)In: NeuroReport, Vol. 14, p. 1867-Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-64952 (URN)
    Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2011-01-13
    3. Cerebrospinal fluid protein patterns in neurodegenerative disease revealed by liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry
    Open this publication in new window or tab >>Cerebrospinal fluid protein patterns in neurodegenerative disease revealed by liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry
    Show others...
    2004 In: Proteomics, Vol. 4, no 12, p. 4010-4018Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92809 (URN)
    Available from: 2005-04-07 Created: 2005-04-07 Last updated: 2011-03-21
    4. Evidence for astrocytosis in ALS demonstrated by 11C(L)-deprenyl-D2 PET
    Open this publication in new window or tab >>Evidence for astrocytosis in ALS demonstrated by 11C(L)-deprenyl-D2 PET
    Show others...
    2007 (English)In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 255, no 1-2, p. 17-22Article in journal (Refereed) Published
    Abstract [en]

    Objective: To use deuterium-substituted [11C](l)-deprenyl PET to depict astrocytosis in vivo in patients with amyotrophic lateral sclerosis (ALS). Background: In human brain, the enzyme MAO-B is primarily located in astrocytes. l-deprenyl binds to MAO-B and autoradiography with 3H-l-deprenyl has been used to map astrocytosis in vitro. Motor neuron loss in ALS is accompanied by astrocytosis and astrocytes may play an active role in the neurodegenerative process. Deuterium-substituted [11C](l)-deprenyl PET provides an opportunity to localize astrocytosis in vivo in the brain of patients with ALS. Methods: Deuterium-substituted [11C](l)-deprenyl PET was performed in seven patients with ALS and seven healthy control subjects. Results: Increased uptake rate of [11C](l)-deprenyl was demonstrated in ALS in pons and white matter. Conclusion: This study provides evidence that astrocytosis may be detected in vivo in ALS by the use of deuterium-substituted [11C](l)-deprenyl PET though further studies are needed to determine whether deuterium-substituted [11C](l)-deprenyl binding tracks disease progression and reflects astrocytosis.

    Keywords
    Amyotrophic lateral sclerosis, ALS, Motor neuron disease, Astrocytosis, PET, MAO-B, Deprenyl
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-10812 (URN)10.1016/j.jns.2007.01.057 (DOI)000245849000003 ()17346749 (PubMedID)
    Available from: 2008-02-01 Created: 2008-02-01 Last updated: 2017-12-11Bibliographically approved
    5. [11C]-PIB imaging in patients with Parkinson's disease: preliminary results
    Open this publication in new window or tab >>[11C]-PIB imaging in patients with Parkinson's disease: preliminary results
    Show others...
    2008 (English)In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 14, no 4, p. 345-347Article in journal (Refereed) Published
    Abstract [en]

    [11C]-PIB positron emission tomography ([11C]-PIB PET) is a sensitive marker of amyloid in Alzheimer's disease (AD), but its specificity has not been fully evaluated. Vascular amyloid-β deposition is common in Parkinson's disease (PD) and α-synuclein, the major component of the Lewy bodies in PD, forms amyloid fibrils. We investigated five apparently cognitively normal PD patients with [11C]-PIB PET. The results were compared to 16 patients with AD and six healthy controls from a previous study. [11C]-PIB retention was not significantly increased in our patients who all had early stage PD. Further studies of more advanced PD patients are warranted.

    Keywords
    Parkinson's disease, PET, PIB, Amyloid, Lewy bodies, α-Synuclein
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-16636 (URN)10.1016/j.parkreldis.2007.07.010 (DOI)000257646500015 ()
    Available from: 2008-05-30 Created: 2008-05-30 Last updated: 2017-12-08Bibliographically approved
    6. Retrospective evaluation of L-[β-11C]-DOPA and FDG PET for the differential diagnosis of parkinsonian syndromes - a long-term follow-up study
    Open this publication in new window or tab >>Retrospective evaluation of L-[β-11C]-DOPA and FDG PET for the differential diagnosis of parkinsonian syndromes - a long-term follow-up study
    Show others...
    (English)Manuscript (Other academic)
    Keywords
    Parkinsonism, Parkinson's disease, multiple system atrophy, positron emission tomography, FDG, (11C)-L-DOPA
    National Category
    Neurology
    Research subject
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-102009 (URN)
    Available from: 2009-04-29 Created: 2009-04-29 Last updated: 2010-01-14
  • 187.
    Johansson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    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.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Engler, Henry
    Department of Nuclear Medicine, University of the Republic, Montevideo, Uruguay.
    Retrospective evaluation of L-[β-11C]-DOPA and FDG PET for the differential diagnosis of parkinsonian syndromes - a long-term follow-up studyManuscript (Other academic)
  • 188.
    Johansson, Anders
    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.
    Continuous delivery of energy or L-dopa: Identifying advantages and limitations of DBS and levodopa-carbidopa intestinal gel in ansence of head-to-head comparisons2012In: Basal Ganglia, Vol. 2, no 4, p. 221-226Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) and levodopa–carbidopa intestinal gel (LCIG) are invasive, efficacious treatments for advanced Parkinson’s disease, but so far head-to-head comparisons are scarce. Although their indications and improvements in motor outcome and quality of life may be broadly similar, these treatment modalities have different modes of action and side effect profiles. This article summarizes a presentation at the 2nd International Conference on Knowledge Gaps in Parkinson’s Disease and other Movement Disorders in Feburary 2012. An overview of the existing evidence for efficacy and adverse events of LCIG and DBS in short- and long-term is provided. Examples of factors at present affecting choice of treatment are given. The obvious knowledge gap is the need to better identify the appropriate time and place to operate patients with Parkinson’s disease. There are major difficulties facing us when trying to resolve this issue. We argue for a registry of patients exposed to these very efficacious, but expensive and potentially harmful, symptomatic treatments.

  • 189.
    Johansson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Savitcheva, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Forsberg, Anders
    Engler, Henry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Långström, Bengt
    Nordberg, Agneta
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    [11C]-PIB imaging in patients with Parkinson's disease: preliminary results2008In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 14, no 4, p. 345-347Article in journal (Refereed)
    Abstract [en]

    [11C]-PIB positron emission tomography ([11C]-PIB PET) is a sensitive marker of amyloid in Alzheimer's disease (AD), but its specificity has not been fully evaluated. Vascular amyloid-β deposition is common in Parkinson's disease (PD) and α-synuclein, the major component of the Lewy bodies in PD, forms amyloid fibrils. We investigated five apparently cognitively normal PD patients with [11C]-PIB PET. The results were compared to 16 patients with AD and six healthy controls from a previous study. [11C]-PIB retention was not significantly increased in our patients who all had early stage PD. Further studies of more advanced PD patients are warranted.

  • 190. Johansson, Dongni
    et al.
    Ericsson, Anders
    Johansson, Anders
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Ohlsson, Fredrik
    Senek, Marina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Spira, Jack
    Thomas, Ilias
    Westin, Jerker
    Bergquist, Filip
    Individualization of levodopa treatment using a microtablet dispenser and ambulatory accelerometry2018In: CNS Neuroscience & Therapeutics, ISSN 1755-5930, E-ISSN 1755-5949, Vol. 24, no 5, p. 439-447Article in journal (Refereed)
  • 191.
    Johansson, S.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Forsberg, L.
    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.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Danderyd, Sweden..
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Landtblom, A-M
    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. Uppsala Univ, Dept Neurosci, Uppsala, Sweden..
    Walentin, F.
    Orebro Univ Hosp, Orebro, Sweden..
    Martin, C.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Danderyd, 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)2016In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, no suppl. 3, p. 336-337Article in journal (Refereed)
  • 192.
    Johansson, S.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Forsberg, L.
    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.
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, 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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Walentin, F.
    Orebro Univ Hosp, Orebro, Sweden..
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, 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 efficacy of natalizumab2015In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, p. 285-286Article in journal (Other academic)
  • 193.
    Johansson, S.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Forsberg, L.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Nordin, N.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Svenningsson, A.
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Lycke, J.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Landtblom, Anne-Marie
    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..
    Nilsson, P.
    Lund Univ, Dept Neurol, Lund, Sweden..
    Dahle, C.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    The IMSE 2 study: a Swedish nationwide pharmaco-epidemiological and genetic study focused on long-term safety and efficacy of fingolimod2015In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, p. 284-285Article in journal (Other academic)
  • 194.
    Jonasson, My
    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.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Development of a clinically feasible [11C]PE2I PET method for differential diagnosis of parkinsonism using reduced scan duration and automated reference region extraction.2017In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 7, no 6, p. 263-274Article in journal (Refereed)
    Abstract [en]

    [11C]PE2I is a highly selective dopamine transporter PET ligand. Parametric images based on dynamic [11C]PE2I scans, showing dopamine transporter availability (BPND) and relative cerebral blood flow (R1), can be used in differential diagnosis of parkinsonism. This work aimed to investigate a shortened scan duration and automated generation of parametric images which are two prerequisites for routine clinical application. Twelve subjects with parkinsonism and seventeen healthy controls underwent 80 min dynamic [11C]PE2I PET scans. BPND and R1 images were generated using cerebellum reference region defined on a co-registered MRI, as well as a supervised cluster analysis (SVCA)-based reference. Initial 20, 30 and 40 min of the scans were extracted and images of standardized uptake value ratio (SUVR) and R1 were computed using MRI- and SVCA-based reference. Correlation was high between striatal 80 min MRI-based BPND and 40 min SVCA-based SUVR-1 (R2=0.95). High correlation was also found between R1 values in striatal and limbic regions (R2≥0.91) whereas correlation was moderate for cortical regions (R2=0.71). The results indicate that dynamic [11C]PE2I scans can be restricted to 40 min and that SVCA can be used for automatic extraction of a reference region. These outcomes will support routine applications of [11C]PE2I PET in clinical settings.

  • 195.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Parametric methods for [11C]PE2I positron emission tomography2012In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 32, no S1, p. S155-S155Article in journal (Other academic)
  • 196.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Validation of parametric methods for [(11)C]PE2I positron emission tomography2013In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 74, p. 172-178Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES

    The radioligand [(11)C]PE2I is highly selective for dopamine transporter (DAT) and can be used in vivo for investigation of changes in DAT concentration, progression of disease and validation of treatment using positron emission tomography (PET). DAT is an important protein for regulation of central dopamine concentration and DAT deficiency has been associated with several neurodegenerative and neuropsychiatric disorders. Accurate parametric images are a prerequisite for clinical application of [(11)C]PE2I. The purpose of this study was to evaluate different methods for producing [(11)C]PE2I parametric images, showing binding potential (BPND) and relative delivery (R1) at the voxel level, using clinical data as well as simulations.

    METHODS

    Investigations were made in twelve subjects either with social anxiety disorder (n=6) or parkinsonian syndrome (n=6), each receiving an 80min dynamic PET scan. All subjects underwent a T1-weighted MRI scan which was co-registered to the PET images and used for definition of regions of interest using a probabilistic template (PVElab). Two basis function implementations (receptor parametric mapping: RPM, RPM2) of the simplified reference tissue model (SRTM) and three multilinear reference tissue models (MRTMo, MRTM and MRTM2) were used for computation of parametric BPND and R1 images. In addition, reference Logan and standard uptake value ratio (SUVr) were investigated. Evaluations of BPND and R1 images were performed using linear regression to compare the parametric methods to region-based analyses with SRTM and cerebellar gray matter as reference region. Accuracy and precision of each method were assessed by simulations.

    RESULTS

    Correlation and slope of linear regression between parametric and region-based BPND and R1 values in both striatum and extra-striatal regions were optimal for RPM (R(2)=0.99 for both BPND and R1; slopes 0.99 and 0.98 for BPND and R1, respectively, in striatum). In addition, accuracy and precision were best for RPM and RPM2.

    CONCLUSION

    The basis function methods provided more robust estimations of the parameters compared to the other models and performed best in simulations. RPM, a basis function implementation of SRTM, is the preferred method for voxel level analysis of [(11)C]PE2I PET studies.

  • 197. Jonsson, L.
    et al.
    Holmen, C.
    Hillert, J.
    Nilsson, P.
    Dahle, C.
    Feltelius, N.
    Sveningsson, A.
    Lycke, J.
    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.
    Martin, C.
    Piehl, F.
    Olsson, T.
    A Swedish nationwide pharmaco-epidemiological and genetic study (IMSE) of the long-term safety and efficacy of natalizumab2014In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, p. 166-166Article in journal (Refereed)
  • 198. Jonsson, L.
    et al.
    Piehl, F.
    Hillert, J.
    Nilsson, P.
    Dahle, C.
    Feltelius, N.
    Svenningsson, A.
    Lycke, J.
    Fagius, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Wallentin, F.
    Martin, C.
    Olsson, T.
    The immunomodulation and multiple sclerosis epidemiology (IMSE) study; a Swedish nationwide pharmaco-epidemiological and genetic study focussed on long-term safety and efficacy of natalizumab (Tysabri)2013In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 11, p. 205-205Article in journal (Other academic)
  • 199.
    Jusufi, Ilir
    et al.
    Univ Calif Davis, Dept Comp Sci, Davis, CA 95616 USA..
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Memedi, Mevludin
    Dalarna Univ, Sch Technol & Business Studies, Comp Engn, Borlange, Sweden..
    Visualization of spiral drawing data of patients with Parkinson's disease2014In: 2014 18Th International Conference On Information Visualisation (IV), 2014, p. 346-350Conference paper (Refereed)
    Abstract [en]

    Patients with Parkinson's disease (PD) need to be frequently monitored in order to assess their individual symptoms and treatment-related complications. Advances in technology have introduced telemedicine for patients in remote locations. However, data produced in such settings lack much information and are not easy to analyze or interpret compared to traditional, direct contact between the patient and clinician. Therefore, there is a need to present the data using visualization techniques in order to communicate in an understandable and objective manner to the clinician. This paper presents interaction and visualization approaches used to aid clinicians in the analysis of repeated measures of spirography of PD patients gathered by means of a telemetry touch screen device. The proposed approach enables clinicians to observe fine motor impairments and identify motor fluctuations of their patients while they perform the tests from their homes using the telemetry device.

  • 200.
    Kagstrom, S.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Leandersson, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Forsberg, L.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Berglund, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Biogen, Med Dept, Upplandsvasby, 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.
    Walentin, F.
    Orebro Univ Hosp, Orebro, Sweden..
    Martin, C.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Piehl, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of natalizumab (IMSE 1)2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, p. 365-366Article in journal (Other academic)
1234567 151 - 200 of 466
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