umu.sePublikasjoner
Endre søk
Begrens søket
45678910 301 - 350 of 629
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 301.
    Keskin, Isil
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    SOD, ORF and ALS: On the role of SOD1 and C9ORF72 in the pathogenesis of ALS2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is characterized by adult-onset degeneration of upper and lower motor neurons. Symptoms begin focally in one muscle and then spread contiguously, resulting in progressive paralysis and death from respiratory failure. Hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause, however, mutations in SOD1 were the first identified and are found in 1-9% of patients. Misfolded SOD1 aggregates in the CNS are hallmarks of ALS associated with SOD1 mutations. However, accumulation of misfolded or aggregated SOD1 protein has also been reported in sporadic and familial ALS without SOD1 mutations, suggesting that wild-type SOD1 could play a role in ALS pathology in general.

    The aims of this thesis are: 1) To describe the resulting disease phenotype and specific characteristics of the SOD1 protein carrying the stable disease- associated mutation L117V. 2) To set up cell-based in vitro models to study the mechanisms of SOD1 misfolding and aggregation under physiologically relevant expression levels. 3) To compare SOD1 activity in patient-derived samples and screen for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations.

    1) We identified a novel L117V SOD1 mutant in two families of Syrian origin that co-segregated with the disease. This mutation was associated with slow disease progression, reduced penetrance and a uniform phenotype. The L117V mutant protein was indistinguishable from wild-type SOD1 in terms of stability, dismutation activity and misfolding in patient-derived cell lines.

    2) We established patient-derived fibroblast and iPSC-MN lines expressing mutant SOD1 at physiological levels as in vitro models to study misfolding and aggregation of SOD1. We investigated the effects of several cellular pathway disturbances on SOD1 misfolding. Misfolded SOD1 was increased by inhibition of the ubiquitin-proteasome pathway in fibroblasts derived from both patients and controls. An age-related decline in proteasome activity could contribute to the late onset of ALS.

    Next, we studied the effects of low oxygen tension on misfolding and aggregation of SOD1 in patient-derived cells. Low O2 tensions were found to markedly increase C57-C146 disulphide reduction, misfolding and aggregation of SOD1. Importantly, the largest effects were detected in iPSC-MNs. This suggests that motor neurons are specifically vulnerable to misfolding and aggregation of SOD1 under low O2 tension.

    3) We compared the enzymatic activity of SOD1 in blood samples from a large number of ALS patients and controls. We screened for potential underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations. No aberrations in copy number, other large structural changes in introns and exons or intronic mutations in the 30-50 bp flanking the exons were found in the 142 outliers, with either very low or very high SOD1 dismutation activities. However, hemoglobinopathies, including thalassemias and iron deficiency anemia, were associated with high SOD1/mg Hb ratios. Erythrocytes from patients with destabilizing SOD1 mutations showed half the normal activity. There were no significant differences in SOD1 activity between control individuals and ALS patients without a coding SOD1 mutation, or carriers of TBK1 mutations or the hexanucleotide repeat expansion in C9ORF72. Our result suggests that SOD1 enzymatic activity is not associated with the disease in non-SOD1 mutation ALS.

  • 302.
    Keskin, Isil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Berdynski, Mariusz
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Polish Academy of Sciences, Warsaw, Poland.
    Hjertkvist, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Rofougaran, Reza
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nilsson, Torbjörn K.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Glass, Jonathan D.
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in ALS patients and their relatives2017Inngår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, nr 5-6, s. 457-463Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To characterise stabilities in erythrocytes of mutant SOD1 proteins, compare SOD1 enzymatic activities between patients with different genetic causes of ALS and search for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations.Methods: Blood samples from 4072 individuals, ALS patients with or without a SOD1 mutation, family members and controls were studied. Erythrocyte SOD1 enzymatic activities normalised to haemoglobin content were determined, and effects of haemoglobin disorders on dismutation assessed. Coding SOD1 sequences were analysed by Sanger sequencing, exon copy number variations by fragment length analysis and by TaqMan Assay.Results: Of the 44 SOD1 mutations found, 75% caused severe destabilisation of the mutant protein but in 25% it was physically stable. Mutations producing structural changes caused halved erythrocyte SOD1 activities. There were no differences in SOD1 activities between patients without a SOD1 mutation and control individuals or carriers of TBK1 mutations and C9orf72(HRE). In the low and high SOD1 activity groups no deviations were found in exon copy numbers and intron gross structures. Thalassemias and iron deficiency were associated with increased SOD1 activity/haemoglobin ratios.Conclusion: Adjunct erythrocyte SOD1 activity analysis reliably signals destabilising SOD1 mutations including intronic mutations that are missed by exon sequencing.

  • 303.
    Keskin, Isil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Berdynski, Mariusz
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hjertkvist, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Rofougaran, Reza
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nilsson, Torbjörn K.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Glass, Jonathan D.
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in erythrocytes in ALS patients and their relativesManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Our objective was to in blood samples from 3723 individuals including ALS patients without a coding SOD1 mutation and 372 control individuals characterize stabilities of mutant SOD1s, compare SOD1 enzymatic activities between patients with different genetic causes of ALS, and search for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations. Erythrocyte SOD1 enzymatic activities normalized to hemoglobin content were determined. Coding SOD1 sequences were analyzed by Sanger sequencing, copy number variations by fragment length analysis and by TaqMan Assay. Hemoglobin disorders were searched for. Of the 46 SOD1 mutations found, ¾ caused severe destabilization of the mutant protein but in ¼ SOD1 was essentially physically stable. Mutations producing structural changes all caused halved SOD activities. There were no differences in SOD1 activities between controls and patients without any detected SOD1 mutations or patients with C9ORF72HRE or TBK1 mutations. In the low and high SOD1 activity groups no deviations were found in exon copy numbers and intron gross structures. Also, no uncommon variants in exon-flanking sequences were detected. Thalassemias and iron deficiency anemia were associated with increased SOD1 activity/hemoglobin ratios. In conclusion, adjunct erythrocyte SOD activity analysis is of value to signal the presence of exon and splice-site-intron mutations that influence the SOD1 structure.

  • 304.
    Keskin, Isil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lange, Dale J.
    Synofzik, Matthis
    Nordström, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Zetterström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Gilthorpe, Jonathan D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Low oxygen tension induces misfolding and aggregation of superoxide dismutase in ALS patient-derived motor neuronsManuskript (preprint) (Annet vitenskapelig)
  • 305.
    Keskin, Isil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lange, Dale J.
    Weber, Markus
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Synofzik, Matthis
    Gilthorpe, Jonathan D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Effects of Cellular Pathway Disturbances on Misfolded Superoxide Dismutase-1 in Fibroblasts Derived from ALS Patients2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 2, artikkel-id e0150133Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mutations in superoxide dismutase-1 (SOD1) are a common known cause of amyotrophic lateral sclerosis (ALS). The neurotoxicity of mutant SOD1s is most likely caused by misfolded molecular species, but disease pathogenesis is still not understood. Proposed mechanisms include impaired mitochondrial function, induction of endoplasmic reticulum stress, reduction in the activities of the proteasome and autophagy, and the formation of neurotoxic aggregates. Here we examined whether perturbations in these cellular pathways in turn influence levels of misfolded SOD1 species, potentially amplifying neurotoxicity. For the study we used fibroblasts, which express SOD1 at physiological levels under regulation of the native promoter. The cells were derived from ALS patients expressing 9 different SOD1 mutants of widely variable molecular characteristics, as well as from patients carrying the GGGGCC-repeat-expansion in C9orf72 and from non-disease controls. A specific ELISA was used to quantify soluble, misfolded SOD1, and aggregated SOD1 was analysed by western blotting. Misfolded SOD1 was detected in all lines. Levels were found to be much lower in non-disease control and the non-SOD1 C9orf72 ALS lines. This enabled us to validate patient fibroblasts for use in subsequent perturbation studies. Mitochondrial inhibition, endoplasmic reticulum stress or autophagy inhibition did not affect soluble misfolded SOD1 and in most cases, detergent-resistant SOD1 aggregates were not detected. However, proteasome inhibition led to uniformly large increases in misfolded SOD1 levels in all cell lines and an increase in SOD1 aggregation in some. Thus the ubiquitin-proteasome pathway is a principal determinant of misfolded SOD1 levels in cells derived both from patients and controls and a decline in activity with aging could be one of the factors behind the mid-to late-life onset of inherited ALS.

  • 306. Khademi, Mohsen
    et al.
    Dring, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wuolikainen, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Al Nimer, Faiez
    Harris, Robert
    Andersson, Magnus
    Brundin, Lou
    Piehl, Fredrik
    Olsson, Tomas
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Multivariate analysis of inflammatory and neuronal injury markers in cerebrospinal fluid of multiple sclerosis: higher levels are associated with younger age2012Inngår i: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 253, nr 1-2, s. 100-100Artikkel i tidsskrift (Annet vitenskapelig)
  • 307. Khademi, Mohsen
    et al.
    Dring, Ann M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Gilthorpe, Jonathan D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wuolikainen, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Al Nimer, Faiez
    Harris, Robert A.
    Andersson, Magnus
    Brundin, Lou
    Piehl, Fredrik
    Olsson, Tomas
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Intense Inflammation and Nerve Damage in Early Multiple Sclerosis Subsides at Older Age: A Reflection by Cerebrospinal Fluid Biomarkers2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 5, s. e63172-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Inflammatory mediators have crucial roles in leukocyte recruitment and subsequent central nervous system (CNS) neuroinflammation. The extent of neuronal injury and axonal loss are associated with the degree of CNS inflammation and determine physical disability in multiple sclerosis (MS). The aim of this study was to explore possible associations between a panel of selected cerebrospinal fluid biomarkers and robust clinical and demographic parameters in a large cohort of patients with MS and controls (n = 1066) using data-driven multivariate analysis. Levels of matrix metalloproteinase 9 (MMP9), chemokine (C-X-C motif) ligand 13 (CXCL13), osteopontin (OPN) and neurofilament-light chain (NFL) were measured by ELISA in 548 subjects comprising different MS subtypes (relapsing-remitting, secondary progressive and primary progressive), clinically isolated syndrome and persons with other neurological diseases with or without signs of inflammation/infection. Principal component analyses and orthogonal partial least squares methods were used for unsupervised and supervised interrogation of the data. Models were validated using data from a further 518 subjects in which one or more of the four selected markers were measured. There was a significant association between increased patient age and lower levels of CXCL13, MMP9 and NFL. CXCL13 levels correlated well with MMP9 in the younger age groups, but less so in older patients, and after approximately 54 years of age the levels of CXCL13 and MMP9 were consistently low. CXCL13 and MMP9 levels also correlated well with both NFL and OPN in younger patients. We demonstrate a strong effect of age on both inflammatory and neurodegenerative biomarkers in a large cohort of MS patients. The findings support an early use of adequate immunomodulatory disease modifying drugs, especially in younger patients, and may provide a biological explanation for the relative inefficacy of such treatments in older patients at later disease stages.

  • 308. Khoo, Sok Kean
    et al.
    Petillo, David
    Kang, Un Jung
    Resau, James H.
    Berryhill, Brian
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Neuman, Leslie A.
    Tan, Aik Choon
    Plasma-Based Circulating MicroRNA Biomarkers for Parkinson's Disease2012Inngår i: Journal of Parkinson's Disease, ISSN 1877-7171, Vol. 2, nr 4, s. 321-331Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The current "gold-standard" for Parkinson's disease (PD) diagnosis is based primarily on subjective clinical rating scales related with motor features. Molecular biomarkers that are objective and quantifiable remain attractive as clinical tools to detect PD prior to its motor onsets.

    Objective: Here, we aimed to identify, develop, and validate plasma-based circulating microRNA (miRNAs) as biomarkers for PD.

    Methods: Global miRNA expressions were acquired from a discovery set of 32 PD/32 controls using microarrays. k-Top Scoring Pairs (k-TSP) algorithm and significance analysis of microarrays (SAM) were applied to obtain comprehensive panels of PD-predictive biomarkers. TaqMan miRNA-specific real-time PCR assays were performed to validate the microarray data and to evaluate the biomarker performance using a new replication set of 42 PD/30 controls. Data was analyzed in a paired PD-control fashion. The validation set was composed of 30 PD, 5 progressive supranuclear palsy, and 4 multiple system atrophy samples from a new clinical site.

    Results: We identified 9 pairs of PD-predictive classifiers using k-TSP analysis and 13 most differentially-expressed miRNAs by SAM. A combination of both data sets produced a panel of PD-predictive biomarkers: k-TSP1 (miR-1826/miR-450b-3p), miR-626, and miR-505, and achieved the highest predictive power of 91% sensitivity, 100% specificity, 100% positive predicted value, and 88% negative predicted value in the replication set. However, low predictive values were shown in the validation set.

    Conclusions: This proof-of-concept study demonstrates the feasibility of using plasma-based circulating miRNAs as biomarkers for neurodegenerative disorders such as PD and shows the challenges of molecular biomarker research using samples from multiple clinical sites.

  • 309.
    Koskinen, Lars-Owe D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sjöberg, Rickard L.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Predicting improvement after surgery for palmar hyperhidrosis2012Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 126, nr 5, s. 324-328Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives Endoscopic transthoracic sympathectomy (ETS) is a surgical procedure used to improve Quality of Life (QoL) in patients with treatment resistant palmar hyperhidrosis (PHH). The aim of this study was to test the hypothesis that low preoperative scores on The Everyday Life Questionnaire (EDLQ) would predict QoL improvement after surgery. Materials and methods Pre- and post-operative QoL scores from a series of 30 consecutive patients who underwent ETS at our institution were analyzed. Results Preoperative QoL scores was a significant predictor of post-operative improvement across all dimensions covered by the questionnaire. Conclusion Preoperative low QoL can be used as a guide in selecting patients with most improved QoL after ETS.

  • 310.
    Koskinen, Lars-Owe D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Olivecrona, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Prostacyclin Influences the Pressure Reactivity in Patients with Severe Traumatic Brain Injury Treated with an ICP-Targeted Therapy2015Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 22, nr 1, s. 26-33Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This prospective consecutive double-blinded randomized study investigated the effect of prostacyclin on pressure reactivity (PR) in severe traumatic brain injured patients. Other aims were to describe PR over time and its relation to outcome. Blunt head trauma patients, Glasgow coma scale a parts per thousand currency sign8, age 15-70 years were included and randomized to prostacyclin treatment (n = 23) or placebo (n = 25). Outcome was assessed using the extended Glasgow outcome scale (GOSE) at 3 months. PR was calculated as the regression coefficient between the hourly mean values of ICP versus MAP. Pressure active/stable was defined as PR a parts per thousand currency sign0. Mean PR over 96 h (PRtot) was 0.077 +/- A 0.168, in the prostacyclin group 0.030 +/- A 0.153 and in the placebo group 0.120 +/- A 0.173 (p < 0.02). There was a larger portion of pressure-active/stable patients in the prostacyclin group than in the placebo group (p < 0.05). Intra-individual changes over time were common. PRtot correlated negatively with GOSE score (p < 0.04). PRtot was 0.117 +/- A 0.182 in the unfavorable (GOSE 1-4) and 0.029 +/- A 0.140 in the favorable outcome group (GOSE 5-8). Area under the curve for prediction of death (ROC) was 0.742 and for favorable outcome 0.628. Prostacyclin influenced the PR in a direction of increased pressure stability and a lower PRtot was associated with improved outcome. The individual PR varied substantially over time. The predictive value of PRtot for outcome was not solid enough to be used in the clinical situation.

  • 311.
    Koskinen, Lars-Owe D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Grayson, David
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Olivecrona, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    The complications and the position of the Codman MicroSensor (TM) ICP device: an analysis of 549 patients and 650 Sensors2013Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 155, nr 11, s. 2141-2148Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Complications of and insertion depth of the Codman MicroSensor ICP monitoring device (CMS) is not well studied. To study complications and the insertion depth of the CMS in a clinical setting. We identified all patients who had their intracranial pressure (ICP) monitored using a CMS device between 2002 and 2010. The medical records and post implantation computed tomography (CT) scans were analyzed for occurrence of infection, hemorrhage and insertion depth. In all, 549 patients were monitored using 650 CMS. Mean monitoring time was 7.0 +/- 4.9 days. The mean implantation depth was 21.3 +/- 11.1 mm (0-88 mm). In 27 of the patients, a haematoma was identified; 26 of these were less than 1 ml, and one was 8 ml. No clinically significant bleeding was found. There was no statistically significant increase in the number of hemorrhages in presumed coagulopathic patients. The infection rate was 0.6 % and the calculated infection rate per 1,000 catheter days was 0.8. The risk for hemorrhagic and infectious complications when using the CMS for ICP monitoring is low. The depth of insertion varies considerably and should be taken into account if patients are treated with head elevation, since the pressure is measured at the tip of the sensor. To meet the need for ICP monitoring, an intraparenchymal ICP monitoring device should be preferred to the use of an external ventricular drainage (EVD).

  • 312.
    Koskinen, Lars-Owe D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Zakelis, Rolandas
    Bartusis, Laimonas
    Ragauskas, Arminas
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Can intracranial pressure be measured non-invasively bedside using a two-depth Doppler-technique?2017Inngår i: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 31, nr 2, s. 459-467Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Measurement of intracranial pressure (ICP) is necessary in many neurological and neurosurgical diseases. To avoid lumbar puncture or intracranial ICP probes, non-invasive ICP techniques are becoming popular. A recently developed technology uses two-depth Doppler to compare arterial pulsations in the intra- and extra-cranial segments of the ophthalmic artery for non-invasive estimation of ICP. The aim of this study was to investigate how well non-invasively-measured ICP and invasively-measured cerebrospinal fluid (CSF) pressure correlate. We performed multiple measurements over a wide ICP span in eighteen elderly patients with communicating hydrocephalus. As a reference, an automatic CSF infusion apparatus was connected to the lumbar space. Ringer's solution was used to create elevation to pre-defined ICP levels. Bench tests of the infusion apparatus showed a random error (95 % CI) of less than ±0.9 mmHg and a systematic error of less than ±0.5 mmHg. Reliable Doppler signals were obtained in 13 (72 %) patients. An infusion test could not be performed in one patient. Thus, twelve patients and a total of 61 paired data points were studied. The correlation between invasive and non-invasive ICP measurements was good (R = 0.74), and the 95 % limits of agreements were -1.4 ± 8.8 mmHg. The within-patient correlation varied between 0.47 and 1.00. This non-invasive technique is promising, and these results encourage further development and evaluation before the method can be recommended for use in clinical practice.

  • 313.
    Koskinen, Lars-Owe D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Runnerstam, Magnus
    Koch, Mona
    FOI, Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
    Karlsson, Britt M.
    FOI, Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
    Cerebral microvascular effects of nimodipine in combination with soman2012Inngår i: Environmental Toxicology and Pharmacology, ISSN 1382-6689, E-ISSN 1872-7077, Vol. 34, nr 3, s. 905-910Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Nimodipine, a calcium antagonist, has been shown to increase the detoxification of soman. In this study the cerebral microcirculatory effects of nimodipine and the acetylcholinesterase inhibitor soman was studied. Anaesthetised rats were administered nimodipine, 10 mg kg(-1) or vehicle intra-peritoneally, and 1 h later exposed to 45 mu g kg(-1) soman intravenously. The regional blood flows were measured using the microsphere method. Nimodipine and soman markedly increased the cerebral blood flow (CBF) and reduced the vascular resistance. Total CBF increased by 146% after nimodipine and by 105% after soman administration. Combined administration of nimodipine and soman caused additional but not fully additive effects on CBF and vascular resistance, indicating possible different mechanisms of the two agents. A part of the nimodipine induced increased detoxification after AChE-inhibition may be associated with this cerebral vasodilation. (C) 2012 Elsevier B.V. All rights reserved.

  • 314.
    Koskinen, Lars-Owe D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Hägglund, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Olivecrona, Magnus
    The relation between brain interstitial clycerol and pressure reactivity in TBI is prostacyclin dependent2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A185-A185Artikkel i tidsskrift (Annet vitenskapelig)
  • 315.
    Koskinen, Lars-owe
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Naredi, Silvana
    Olivecrona, Magnus
    Ten-year follow-up of patients in a double blinded randomized study on prostacyclin treatment in severe traumatic brain injury2017Inngår i: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 31, nr 6-7, s. 770-771Artikkel i tidsskrift (Annet vitenskapelig)
  • 316.
    Koskinen, Lars-Owe
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Olivecrona, Magnus
    Department of Anaesthesia and Intensive Care, University of Örebro, Sweden.
    Grande, P. O.
    Department of Clinical Science in Lund, Anaesthesia and Intensive Care, Lund University, Sweden.
    Severe traumatic brain injury management and clinical outcome using the Lund concept2014Inngår i: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 283, s. 245-255Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    This review covers the main principles of the Lund concept for treatment of severe traumatic brain injury. This is followed by a description of results of clinical studies in which this therapy or a modified version of the therapy has been used. Unlike other guidelines, which are based on meta-analytical approaches, important components of the Lund concept are based on physiological mechanisms for regulation of brain volume and brain perfusion and to reduce transcapillary plasma leakage and the need for plasma volume expanders. There have been nine non-randomized and two randomized outcome studies with the Lund concept or modified versions of the concept. The non-randomized studies indicated that the Lund concept is beneficial for outcome. The two randomized studies were small but showed better outcome in the groups of patients treated according to the modified principles of the Lund concept than in the groups given a more conventional treatment. This article is part of a Special Issue entitled: Brain compensation. For good?. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  • 317.
    Kotikawatte, Thivra
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Suppression of Mu waves in the motor cortex during visualisation of right hand movement2016Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 318.
    Kristensen, Bo Traberg
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stroke in young adults in northern Sweden1998Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Objectives. To study different aspects of cerebral venous and arterial occlusive disease including cerebrospinalfluid hydrodynamics, epidemiology, aetiology, genetics, metabolic and haemostatic disorders, andcognitive function in young adults in Northern Sweden.

    Methods. Cerebrospinal fluid hydrodynamics were investigated with a constant pressure infusion methodin patients with superior sagittal sinus thrombosis. Ten patients were studied with serial examinations, upto 15 years after the onset of the disease.

    Epidemiological data on ischaemic stroke in young adults aged 18 to 44 years were collected to calculateincidence and mortality based on the WHO Northern Sweden MONICA register of acute strokeevents. One hundred and seven consecutive patients aged 18-44 years with ischaemic stroke referred toUmeå university hospital were studied prospectively during a five-year period and were extensively evaluatedaccording to a standardized protocol. During follow-up at least three months after onset 102 and 80patients, respectively, were evaluated for disturbances in the fibrinolytic system and in the metabolism ofhomocysteine. A comprehensive neuropsychological battery was performed in a subset of 20 patients withinfratentorial infarcts.

    Results and conclusions. All patients with superior sagittal sinus thrombosis demonstrated a marked increasein intracranial pressure due to raised pressure in the sagittal sinus. A striking feature was the persistentintracranial pressure increase with only a slow decline over time.

    The incidence rate for ischaemic stroke was higher than previously reported from most countries inWestern Europe. The higher incidence was not explained by a higher prevalence of atherosclerotic vasculopathy. In spite of extensive evaluation, including advanced cardiac imaging, the cause of ischaemic strokein young adults still remains uncertain or unknown in most cases.

    Patients had lowered tissue plasminogen activator activity and increased plasminogen activator inhibitortype 1 activity. Increased fibrinogen levels and tissue plasminogen activator mass concentration wereindependently associated with ischaemic stroke. Metabolic perturbations were closely interrelated with tissueplasminogen activator and plasminogen activator inhibitor type 1 activity. Elevated plasma fibrinogenlevels and abnormalities in the fibrinolytic system in conjunction with metabolic perturbations may be importantcontributors to an increased stroke risk among young adults.

    Stroke patients had an exaggerated increase in total homocysteine levels after methionine loading.Abnormal responsivity to methionine loading was associated with higher tissue plasminogen activatormass concentration, plasminogen activator inhibitor 1 levels and lower tissue plasminogen activator activity. Abnormal homocysteine metabolism may provide an additional thrombogenetic risk, partly mediatedby interactions with the fibrinolytic system.

    Circumscribed infratentorial lesions (mainly cerebellar) impaired central aspects of attention andworking memory, and inflicted damage upon visuospatial skills. In contrast, these patients may not sufferfrom global intellectual impairment and difficulties with respect to memory for previous events. The prognosisis favorable in terms of neurological deficits and handicap, but cognitive disability may be the mostsignificant problem in adapting to their former occupations.Key w ords. Cerebral venous thrombosis, cerebrospinal fluid dynamics, ischaemic stroke, young adults, epidemiology,fibrinolysis, homocysteine, cerebellar infarct, neuropsychology.

  • 319. Kristian, B.
    et al.
    Wachtmeister, K.
    Stefan, F.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Retigabine as add-on treatment of refractory epilepsy a cost-utility study in a Swedish setting2013Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, nr 6, s. 419-426Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives To calculate comparative incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) and net marginal benefits for retigabine as add-on treatment for patients with uncontrolled focal seizures as compared to add-on lacosamide treatment and no add-on treatment, respectively. Materials & Methods Calculations were performed using a validated decision-tree model. The study population consisted of adult patients with focal-onset epilepsy in published randomized placebo-controlled add-on trials of retigabine or lacosamide. Healthcare utilization and QALY for each treatment alternative were calculated. Probabilistic sensitivity analysis was performed using the specification of this model as a basis for Monte Carlo simulations. 2009 prices were used for all costs. Results Results were reported for a 2-year follow-up period. Retigabine add-on treatment was both more effective and less costly than lacosamide add-on treatment, and the cost per additional QALY for the retigabine no add-on (standard) therapy comparison was estimated at 2009Euro 15,753. Using a willingness-to-pay threshold for a QALY of Euro 50,000, the net marginal values were estimated at 2009Euro 605,874 for retigabine vs lacosamide and 2009Euro 2,114,203 for retigabine vs no add-on, per 1,000 patients. The probabilistic analyses showed that the likelihood that retigabine treatment is cost-effective is at least 70%. Conclusions The estimated cost per additional QALY, for the retigabine vs no add-on treatment comparison, is well within the range of newly published estimates of willingness to pay for an additional QALY. Thus, add-on retigabine treatment for people with focal-onset epilepsy with no/limited response to standard antiepileptic treatment appears to be cost-effective.

  • 320. Kurowska, Zuzanna
    et al.
    Jewett, Michael
    Brattås, Per Ludvik
    Jimenez-Ferrer, Itzia
    Kenez, Xuyian
    Björklund, Tomas
    Nordström, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Brundin, Patrik
    Swanberg, Maria
    Identification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson's Disease2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikkel-id 31701Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Motor symptoms in Parkinson's disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygosity for Engrailed-1 (En1), one of the key factors for programming and maintenance of DNs, results in a parkinsonian phenotype featuring progressive degeneration of DNs in substantia nigra pars compacta (SNpc), decreased striatal dopamine levels and swellings of nigro-striatal axons in the SwissOF1-En1+/- mouse strain. In contrast, C57Bl/6-En1+/- mice do not display this neurodegenerative phenotype, suggesting that susceptibility to En1 heterozygosity is genetically regulated. Our goal was to identify quantitative trait loci (QTLs) that regulate the susceptibility to PD-like neurodegenerative changes in response to loss of one En1 allele. We intercrossed SwissOF1-En1+/- and C57Bl/6 mice to obtain F2 mice with mixed genomes and analyzed number of DNs in SNpc and striatal axonal swellings in 120 F2-En1+/- 17 week-old male mice. Linkage analyses revealed 8 QTLs linked to number of DNs (p = 2.4e-09, variance explained = 74%), 7 QTLs linked to load of axonal swellings (p = 1.7e-12, variance explained = 80%) and 8 QTLs linked to size of axonal swellings (p = 7.0e-11, variance explained = 74%). These loci should be of prime interest for studies of susceptibility to Parkinson's disease-like damage in rodent disease models and considered in clinical association studies in PD.

  • 321.
    Lagebrant, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Choice of treatment of subdural hematomas in shunted hydrocephalus patients2016Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 322.
    Lampa, Ewa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Wänman, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Nordh, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Häggman-Henrikson, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Department of Orofacial pain and Jaw function, Malmö University, Malmö, Sweden.
    Effects on jaw function shortly after whiplash trauma2017Inngår i: Journal of Oral Rehabilitation, ISSN 0305-182X, E-ISSN 1365-2842, Vol. 44, nr 12, s. 941-947Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Normal jaw function involves muscles and joints of both jaw and neck. A whiplash trauma may disturb the integrated jaw-neck sensory-motor function and thereby impair chewing ability; however, it is not known if such impairment is present shortly after a neck trauma or develops over time. The aim was to evaluate jaw function after a recent whiplash trauma. Eighty cases (47 women) were examined within 1 month after a whiplash trauma and compared to 80 controls (47 women) without neck trauma. Participants completed the Jaw disability checklist (JDC) and Neck Disability Index (NDI) questionnaires and performed a 5-minute chewing test. Elicited fatigue and pain during chewing were noted, and group differences were evaluated with Fisher's exact test and Mann-Whitney U-test. Compared to controls, cases had higher JDC (P<.0001) and NDI scores (15% vs 2%, P<.0001), and reported more fatigue (53% vs 31%, P=.006) and pain (30% vs 10%, P=.003) during the chewing test. Cases also had a shorter onset time for fatigue and pain (both P=.001) Furthermore, cases reporting symptoms during chewing had higher JDC and NDI scores compared to cases not reporting symptoms (both P=.01). Symptoms mainly occurred in the trigeminal area for both groups, but also in spinal areas more often for cases than for controls. Taken together, the results indicate that jaw-neck sensory-motor function is impaired already within 1month after a whiplash trauma. The association between neck disability and jaw impairment underlines the close functional relationship between the regions, and stresses the importance of multidisciplinary assessment.

  • 323.
    Lampa, Ewa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Wänman, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Nordh, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stålnacke, Britt-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Häggman-Henrikson, Birgitta
    The Course of Orofacial Pain and Jaw Disability after Whiplash Trauma: A 2-year Prospective StudyManuskript (preprint) (Annet vitenskapelig)
  • 324. Lange, Dale J.
    et al.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Remanan, Rahul
    Marklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Benjamin, Daniel
    Pyrimethamine decreases levels of SOD1 in leukocytes and cerebrospinal fluid of ALS patients: A phase I pilot study2013Inngår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, Vol. 14, nr 3, s. 199-204Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The mutated SOD1 protein appears to have a gene dose-dependent effect on the severity and progression of ALS. Lowering of SOD1 protein levels might reduce severity and progression of the disease. The antimalarial drug pyrimethamine (PYR) was identified to cause a dose-dependent reduction in SOD1 protein levels in human cells in vitro. To determine if there was a similar effect in humans, we performed a phase I pilot study in 16 ALS patients with SOD1 mutations, 18 weeks in duration. Blood samples were obtained during all visits. The actin normalized leukocyte SOD1 levels were analyzed using Western blot. SOD1 content in the cerebrospinal fluid (CSF) was determined by ELISA and the SOD1 enzymic activity by spectrophotometric analysis using KO2. Clinical assessment of disease severity was assessed using Appel ALS scale and ALSFRS-R. The leukocyte SOD1 levels showed a significant reduction (p < 0.0001) by the third study visit and this reduction was sustained throughout the remainder of the study. CSF also showed a decrease in SOD1 protein content and enzymic activity in the two patients so tested. Thus, PYR use may be associated with a reduction in SOD1 in ALS patients. The significance is uncertain and further detailed study is required.

  • 325. Lange, Dale J.
    et al.
    Shahbazi, Mona
    Silani, Vincenzo
    Ludolph, Albert C.
    Weishaupt, Jochen H.
    Ajroud-Driss, Senda
    Fields, Kara G.
    Remanan, Rahul
    Appel, Stanley H.
    Morelli, Claudia
    Doretti, Alberto
    Maderna, Luca
    Messina, Stefano
    Weiland, Ulrike
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Neurology, Ulm University, Ulm, Germany.
    Pyrimethamine Significantly Lowers Cerebrospinal Fluid Cu/Zn Superoxide Dismutase in Amyotrophic Lateral Sclerosis Patients with SOD1 Mutations2017Inngår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 81, nr 6, s. 837-848Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Cu/Zn superoxide dismutase (SOD1) reduction prolongs survival in SOD1-transgenic animal models. Pyrimethamine produces dose-dependent SOD1 reduction in cell culture systems. A previous phase 1 trial showed pyrimethamine lowers SOD1 levels in leukocytes in patients with SOD1 mutations. This study investigated whether pyrimethamine lowered SOD1 levels in the cerebrospinal fluid (CSF) in patients carrying SOD1 mutations linked to familial amyotrophic lateral sclerosis (fALS/SOD1). Methods: A multicenter (5 sites), open-label, 9-month-duration, dose-ranging study was undertaken to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in fALS/SOD1. All participants underwent 3 lumbar punctures, blood draw, clinical assessment of strength, motor function, quality of life, and adverse effect assessments. SOD1 levels were measured in erythrocytes and CSF. Pyrimethamine was measured in plasma and CSF. Appel ALS score, ALS Functional Rating Scale-Revised, and McGill Quality of Life Single-Item Scale were measured at screening, visit 6, and visit 9. Results: We enrolled 32 patients; 24 completed 6 visits (18 weeks), and 21 completed all study visits. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit 6 (p<0.001) with a mean reduction of 13.5% (95% confidence interval [CI] 58.4-18.5) and at visit 9 (p<0.001) with a mean reduction of 10.5% (95% CI55.2-15.8). Interpretation: Pyrimethamine is safe and well tolerated in ALS. Pyrimethamine is capable of producing a significant reduction in total CSF SOD1 protein content in patients with ALS caused by different SOD1 mutations. Further long-term studies are warranted to assess clinical efficacy.

  • 326.
    Larsson, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Israelsson, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Epilepsy, headache, and abdominal pain after shunt surgery for idiopathic normal pressure hydrocephalus: the INPH-CRasH study2017Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE Adverse events related to shunt surgery are common and might have a negative effect on outcome in patients with idiopathic normal pressure hydrocephalus (INPH). The authors' objectives were to establish the frequencies of epilepsy, headache, and abdominal pain and determine their impact on patient quality of life (QOL), in long-term follow-up after shunt surgery for INPH.

    METHODS One hundred seventy-six shunt-treated patients with INPH (mean age 74 years) and 368 age- and sex-matched controls from the population were included. The mean follow-up time after surgery was 21 months (range 6-45 months). Each participant answered a questionnaire regarding present frequency and severity of headache and abdominal pain. Confirmed diagnoses of epilepsy and all prescriptions for antiepileptic drugs (AEDs) before and after shunt surgery for INPH were gathered from national registries. Equivalent presurgical and postsurgical time periods were constructed for the controls based on the date of surgery (the division date for controls is referred to as virtual surgery). All registry data covered a mean period of 6 years (range 3-8 years) before surgery/virtual surgery and 4 years (range 2-6 years) after surgery/virtual surgery. Provoked epileptic seizures were excluded. Patient QOL was assessed with the EuroQoL 5-dimension 5-level instrument.

    RESULTS Epilepsy was more common in shunt-treated patients with INPH than in controls (4.5% vs 1.1%, respectively; p = 0.023), as was treatment with AEDs (14.8% vs 7.3%, respectively; p = 0.010). No difference was found between the populations before surgery/virtual surgery (epilepsy, 2.3% [INPH] vs 1.1% [control], p = 0.280; AED treatment, 8.5% [INPH] vs 5.4% [control], p = 0.235). New-onset epilepsy and new AED treatment after surgery/virtual surgery were more common in INPH (epilepsy, 2.3% [INPH] vs 0.0% [control], p = 0.011; AED, 8.5% [INPH] vs 3.3% [control], p = 0.015). At follow-up, more patients with INPH than controls experienced headache several times per month or more often (36.1% vs 11.6%, respectively; p < 0.001). Patients with INPH and unilateral headache had more right-sided headaches than controls (p = 0.038). Postural headache was experienced by 16% (n = 27 of 169) of the patients with INPH. Twenty percent (n = 35) of the patients with INPH had persistent abdominal pain. Headache was not correlated to lower QOL. The study was underpowered to draw conclusions regarding QOL in patients with INPH who had epilepsy and abdominal pain, but the finding of no net difference in mean QOL indicates that no correlation between them existed.

    CONCLUSIONS Epilepsy, headache, and abdominal pain are common in long-term follow-up in patients after shunt surgery for INPH and are more common among patients with INPH than in the general population. All adverse events, including mild and moderate ones, should be considered during postoperative follow-ups and in the development of new methods for shunt placement.

  • 327.
    Laurell, Katarina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Artto, Ville
    Bendtsen, Lars
    Hagen, Knut
    Häggström, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linde, Mattias
    Söderström, Lars
    Tronvik, Erling
    Wessman, Maija
    Zwart, John Anker
    Kallela, Mikko
    Premonitory symptoms in migraine: a cross-sectional study in 2714 persons2016Inngår i: Cephalalgia, ISSN 0333-1024, E-ISSN 1468-2982, Vol. 36, nr 10, s. 951-959Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: To describe the frequency and number of premonitory symptoms (PS) in migraine, the co-occurrence of different PS, and their association with migraine-related factors.

    METHODS: In this cross-sectional study, a validated questionnaire was sent to Finnish migraine families between 2002 and 2013 to obtain data on 14 predefined PS, migraine diagnoses, demographic factors, and migraine characteristics. The estimated response rate was 80%.

    RESULTS: Out of 2714 persons, 2223 were diagnosed with migraine. Among these, 77% reported PS, with a mean number of 3.0 symptoms compared to 30% (p < 0.001) and 0.5 symptoms (p < 0.001) among 491 persons with non-migraine headaches. Yawning was the most commonly reported symptom (34%) among migraineurs. Females reported PS more frequently than males (81 versus 64%, p < 0.001) and experienced a higher number of different symptoms (mean 3.3 versus 1.8, p < 0.001). All measures of migraine severity were associated with a higher burden of PS. Light and sound sensitivity showed the highest co-occurrence (kappa = 0.51, 95% CI 0.47-0.55). In a generalized linear model, age, gender, higher frequency, duration and intensity of headache, reduced working capacity, most aura symptoms, and associated symptoms of the headache phase were significantly associated with an increased in the number of PS.

    CONCLUSION: PS are experienced by a majority of migraineurs. More severe migraine is associated with a higher burden of PS. Since the material was not entirely representative of the general population of migraineurs, caution should be exercised in generalizing the results.

  • 328. Lawley, Justin S.
    et al.
    Levine, Benjamin D.
    Williams, Michael A.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Polaner, David M.
    Subudhi, Andrew W.
    Hackett, Peter H.
    Roach, Robert C.
    Cerebral spinal fluid dynamics: effect of hypoxia and implications for high-altitude illness2016Inngår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 120, nr 2, s. 251-262Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The pathophysiology of acute mountain sickness and high-altitude cerebral edema, the cerebral forms of high-altitude illness, remain uncertain and controversial. Persistently elevated or pathological fluctuations in intracranial pressure are thought to cause symptoms similar to those reported by individuals suffering cerebral forms of high-altitude illness. This review first focuses on the basic physiology of the craniospinal system, including a detailed discussion of the long-term and dynamic regulation of intracranial pressure. Thereafter, we critically examine the available literature, based primarily on invasive pressure monitoring, that suggests intracranial pressure is acutely elevated at altitude due to brain swelling and/or elevated sagittal sinus pressure, but normalizes over time. We hypothesize that fluctuations in intracranial pressure occur around a slightly elevated or normal mean intracranial pressure, in conjunction with oscillations in arterial PO2 and arterial blood pressure. Then these modest fluctuations in intracranial pressure, in concert with direct vascular stretch due to dilatation and/or increased blood pressure transmission, activate the trigeminal vascular system and cause symptoms of acute mountain sickness. Elevated brain water (vasogenic edema) may be due to breakdown of the blood-brain barrier. However, new information suggests cerebral spinal fluid flux into the brain may be an important factor. Regardless of the source (or mechanisms responsible) for the excess brain water, brain swelling occurs, and a "tight fit" brain would be a major risk factor to produce symptoms; activities that produce large changes in brain volume and cause fluctuations in blood pressure are likely contributing factors.

  • 329.
    Leckstroem, Daniel
    et al.
    London, England.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Goldsmith, David
    London, England.
    The trials and tribulations of vitamin D: time for the ‘sunshine’ vitamin to come in out of the cold – or just more broken promises?2014Inngår i: Expert review of Endocrinology & Metabolism, ISSN 1744-6651, Vol. 9, nr 4, s. 327-344Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We are presently faced with the competing notions of modern life being a ‘state of vitamin D depletion’, implying a widespread need to supplement with vitamin D, or, the opposite view, which is that the present evidence can only support at best selective targeted vitamin D intervention. This is important as there is evidence that over the last 40–50 years there were downwards global trends in serum 25(OH)D concentrations, while individual consumption of vitamin D as supplements rose. For this reason and many others, a large population-based interventional study, the VITAL trial, was designed to try to establish the health value of vitamin D supplementation. VITAL is a huge primary prevention trial looking at the effects of vitamin D repletion in preventing cancer and cardiovascular disease in a fundamentally healthy population. This may seem an unusual approach given that what we mostly know about vitamin D is that is has some effects on the skeleton. This review looks to explore current knowledge about vitamin D in health and disease, and at how this is now undergoing significant reappraisal and revision. We will carefully critique the VITAL study design to see if it will allow for the construction of the detailed portfolio of clinical evidence so urgently needed to allow us better to understand role of vitamin D supplementation in health and disease. 

  • 330. Lee, Teresa
    et al.
    Li, Yun R
    Ingre, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Weber, Markus
    Grehl, Torsten
    Gredal, Ole
    de Carvalho, Mamede
    Meyer, Thomas
    Tysnes, Ole-Björn
    Auburger, Georg
    Gispert, Suzana
    Bonini, Nancy M
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Gitler, Aaron D
    Ataxin-2 intermediate-length polyglutamine expansions in European ALS patients2011Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 20, nr 9, s. 1697-1700Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease primarily affecting motor neurons. We recently identified intermediate-length polyglutamine (polyQ) expansions (27-33 Qs) in ataxin 2 as a genetic risk factor for sporadic ALS in North American ALS patients. To extend these findings, we assessed the ataxin 2 polyQ repeat length in 1294 European ALS patients and 679 matched healthy controls. We observed a significant association between polyQ expansions and ALS (>30 Qs; P= 6.2 × 10(-3)). Thus, intermediate-length ataxin 2 polyQ repeat expansions are associated with increased risk for ALS also in the European cohort. The specific polyQ length cutoff, however, appears to vary between different populations, with longer repeat lengths showing a clear association. Our findings support the hypothesis that ataxin 2 plays an important role in predisposing to ALS and that polyQ expansions in ataxin 2 are a significant risk factor for the disease.

  • 331.
    Lehtipalo, Stefan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Koskinen, Lars Ove
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Johansson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Kolmodin, Jane
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Biber, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Continuous interscalene brachial plexus block for postoperative analgesia following shoulder surgery1999Inngår i: Acta Anaesthesiol Scand, Vol. 43, nr 3, s. 258-64Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Severe postoperative pain is a well-known problem following shoulder surgery. This study evaluates the clinical efficacy of continuous interscalene brachial plexus block, patient-controlled analgesia, and morphine (i.v. and i.m.) for postoperative analgesia in this setting. METHODS: Thirty patients, scheduled for acromioplasty during general anesthesia, were randomly allocated to one of three different postoperative pain management groups. Group MO received morphine (5 mg i.m. and 2 mg i.v.) when visual analogue pain score (VAS) > 3, group PL received a continuous interscalene brachial plexus block with bupivacaine (1.25 mg kg-1 + 0.25 mg kg-1 h-1) and group PCA received patient-controlled analgesia with morphine (bolus 1 mg). Postoperative pain relief was assessed (24 h) by VAS, circulatory and respiratory stress parameters (heart rate, systemic arterial pressure and respiratory rate) and stress metabolites (glucose, lactate, glycerol by abdominal subcutaneous microdialysis). RESULTS: Pain relief in the PL group was effective (VAS < 3) and significantly more potent than in groups MO and PCA, except at 16 and 20 h. Lactate was significantly increased in the PL group, glucose was significantly increased in all groups, while glycerol showed a variable pattern. There were no significant stress metabolite differences among groups. VAS showed no statistical correlation with microdialysate, respiratory or circulatory data. CONCLUSION: Successful continuous interscalene brachial plexus block provides very good pain relief following shoulder surgery and is superior to the other methods studied. However, we were unable to demonstrate a correlation between VAS pain scores and stress indicators in metabolic, circulatory and respiratory parameters.

  • 332.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hansson, William
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Three-day CSF drainage barely reduces ventricular size in normal pressure hydrocephalus2012Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, nr 3, s. 237-242Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: External lumbar drainage (ELD) of CSF is a test to determine the suitability of a shunt for patients with normal pressure hydrocephalus (NPH), but its effect on ventricular volume is not known. This study investigates the effect of 3-day ELD of 500 mL on ventricular size and clinical features in patients with idiopathic NPH.

    Methods: Fifteen patients were investigated in a 1.5-T MRI scanner before and after ELD. Ventricular volume was measured manually. Clinical features involved motor and cognitive functions, testing primarily gait and attention. Reduction in ventricular volume was correlated to total drain volume and clinical parameters. Statistical tests were nonparametric, and p < 0.05 was required for significance.

    Results: Drain volume was 415 mL (median 470 mL, range 160-510 mL). Ventricular size was reduced in all patients, averaging 3.7 mL (SD 2.2 mL, p < 0.001), which corresponded to a 4.2% contraction. The ratio of volume contraction to drain volume was only 0.9%. Seven patients improved in gait and 6 in attention. Ventricular reduction and total drain volume correlated neither with improvement nor with each other. The 7 patients with the largest drain volumes (close to 500 mL), had ventricular changes varying from 1.3 to 7.5 mL.

    Conclusions: Clinical improvement occurs in patients with NPH after ELD despite unaltered ventricles, suggesting that ventricular size is of little relevance for postshunt improvement or determining shunt function. The clinical effect provided by ELD, mimicking shunting, is probably related to the recurring CSF extractions rather than to the cumulative effect of the drainage on ventricular volume. Neurology(R) 2012;79:237-242

  • 333.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hansson, William
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Diffusion tensor imaging and correlations to Parkinson rating scales2013Inngår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 260, nr 11, s. 2823-2830Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The contribution of various brain areas to the overall progression of Parkinson's disease remains to be determined. In this study, we apply MRI diffusion tensor imaging to investigate how alterations in diffusion relate to phenotype and symptoms measured by clinical rating scales. Sixty-four patients were investigated at baseline and three follow-ups (1, 3 and 5 years). Thirty-six patients remained in the last follow-up. Regions of interests included frontal white matter, basal ganglia, thalamus, and cerebellum. Scoring on the Unified Parkinson's Disease Rating Scale (UPDRS) I, II, III, Hoehn and Yahr (HY) scale and the Schwab and England scale (SE) was determined. Mean, radial, and axial diffusion and fractional anisotropy were modeled with phenotype and clinical scales in a multivariate/univariate analysis correcting for other covariates. Significance was set at 0.05 Bonferroni corrected. All rating scales except UPDRS III significantly correlated to the diffusion measures, as did clinical phenotype. Specifically, putamen, globus pallidus, and thalamus demonstrated higher diffusion with worsening scores. Diffusion in thalamus was higher in the tremor dominant phenotype than in postural imbalance and gait disturbance. Decline in overall functionality (UPDRS II and SE scale), including mental status (UPDRS I) and stage of the disease (HY scale), in Parkinson's disease is related to altered diffusion in the lentiform nucleus and thalamus. Motor function is not mirrored in diffusion changes, possibly due to medication. Tremor dominant PD patients show diffusion alterations in the thalamus, but the significance of this for tremor generation remains to be determined.

  • 334.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Holmlund, Henny
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Frontal white matter injuries predestine gait difficulties in Parkinson's disease2016Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 134, nr 3, s. 210-218Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: This study applies diffusion tensor imaging (DTI) to determine differences in neuronal integrity between motor phenotypes in Parkinson's disease. Material and Methods: One hundred and twenty-two patients (47 females, mean age = 70.3 years) were included at baseline. Forty patients were tremor dominant (TD), 64 had postural imbalance and gait difficulty (PIGD), and 18 patients were indeterminate. The DTI was repeated after one, three and 5 years, including reassessment of phenotype. DTI was quantified using fractional anisotropy (FA), and mean, radial and axial diffusion. Targeted white matter involved six regions of interests (ROIs) in prefrontal cortex (PFC), the entrance to the external capsule (EEC) and lateral to the horn of the anterior ventricle (LVAH). Grey matter involved the basal ganglia. Data were analysed using mixed linear models with P < 0.05 (Bonferroni corrected) as significance threshold. Results: PIGD and Indeterminate had reduced FA and axial diffusion in PFC, EEC and LVAH compared to Tremor dominant (P < 0.05). Basal ganglia showed no differences. Post hoc analysis showed that FA correlated negatively, and mean and radial diffusion positively, to PIGD symptoms in EEC, LVAH and four ROIs in PFC (P < 0.05). Tremor symptoms showed no correlations. Patients converting to PIGD and Indeterminate had lower FA, and higher mean and radial diffusion, at baseline in EEC, LVAH and four areas in PFC compared to non-converting patients (P < 0.05). Conclusion: Degeneration in frontal white matter is connected to PIGD symptoms in Parkinson's disease and if present at an early stage, the risk for conversion to the PIGD phenotype increases.

  • 335.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Johansson, Anna-Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Domellöf, Erik
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Rönnqvist, Louise
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Alterations in white matter microstructure are associated with goal-directed upper-limb movement segmentation in children born extremely preterm2017Inngår i: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 38, s. 5051-5068Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Altered white matter microstructure is commonly found in children born preterm (PT), especially those born at an extremely low gestational age (GA). These children also commonly show disturbed motor function. This study explores the relation between white matter alterations and upperlimb movement segmentation in 41 children born PT (19 girls), and 41 children born at term (18 girls) at 8 years. The PT group was subdivided into extremely PT (E-PT; GA = 25–27 weeks, N = 10), very PT (V-PT; GA = 28–32 weeks, N = 13), and moderately PT (M-PT; GA = 33–35 weeks, N = 18). Arm/hand preference (preferred/non-preferred) was determined through object interactions and the brain hemispheres were designated accordingly. White matter alterations were assessed using diffusion tensor imaging in nine areas, and movement segmentation of the body-parts head, shoulder, elbow, and wrist were registered during a unimanual goal-directed task. Increased movement segmentation was demonstrated consistently on the preferred side in the E-PT group compared with the term born group. Also compared with the term born peers, the E-PT group demonstrated reduced fractional anisotropy (FA) in the cerebral peduncle (targeting the corticospinal tract) in the hemisphere on the non-preferred side and in the splenium of corpus callosum. In contrast, in the anterior internal capsule on the preferred side, the E-PT group had increased FA. Lower FA in the cerebral peduncle, but higher FA in the anterior internal capsule, was associated with increased movement segmentation across body-parts in a contralateral manner. The results suggest that impaired development of sensorimotor tracts in E-PT children could explain a sub-optimal spatiotemporal organization of upper-limb movements.

  • 336.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eklund, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Diffusion tensor imaging reveals supplementary lesions to frontal white matter in Idiopathic normal pressure hydrocephalus2011Inngår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 68, nr 6, s. 1586-1593Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:: Idiopathic normal pressure hydrocephalus (INPH) is associated with white matter lesions, but the extent and severity of the lesions do not cohere with symptoms or improvement after shunting, implying the presence of further, yet undisclosed, injuries to white matter in INPH. OBJECTIVE:: To apply diffusion tensor imaging (DTI) to explore white matter lesions in patients with INPH before and after drainage of cerebrospinal fluid (CSF). METHODS:: Eighteen patients and ten controls were included. DTI was performed in a 1.5T MRI scanner before and after three-day drainage of 400 ml of CSF. Regions of interest included corpus callosum, capsula interna, frontal and lateral periventricular white matter, and centrum semiovale. White matter integrity was quantified by assessing fractional anisotropies (FA) and apparent diffusion coefficients (ADC), comparing them between patients and controls and between patients before and after drainage. The significance level corresponded to 0.05 (Bonferroni corrected). RESULTS:: Decreased FA in patients was found in three regions (p<0.002, p<0.001 and p<0.0001) in anterior frontal white matter, whereas elevated ADC was found in genu corpus callosum (p<0.0001) and areas of centrum semiovale associated to the precentral gyri (p<0.002). Diffusion patterns in these areas did not change after drainage. CONCLUSION:: DTI reveals subtle injuries - interpreted as axonal loss and gliosis - to anterior frontal white matter where high-order motor systems between frontal cortex and basal ganglia travel, further supporting the notion that motor symptoms in INPH are caused by a chronic ischemia to the neuronal systems involved in the planning processes of movements.

  • 337.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Diffusion measures in early stage parkinsonism: controversial findings including hemispheric lateralisation2013Inngår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 19, nr 4, s. 469-471Artikkel i tidsskrift (Fagfellevurdert)
  • 338.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Fractional anisotropy in the substantia nigra in Parkinson's disease: a complex picture2015Inngår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 22, nr 10, s. 1410-1416Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and purpose: This study employs magnetic resonance imaging (MRI) diffusion tensor imaging to compare diffusion measures in the brains of patients with Parkinson's disease (PD) with healthy controls using longitudinal data. Methods: One-hundred and twenty-two patients and 34 controls were included at baseline. The MRI investigations were repeated after 1, 3 and 5 years. The diffusion measures were quantified using fractional anisotropy and mean, radial and axial diffusion (FA, MD, RD, AD). Regions of interest included the anterior, middle and posterior substantia nigra (SN), but also other areas. Linear models were used to test for the effect of disease and hemispheric lateralization. The P value was set at 0.05 (Bonferroni corrected). Results: Fractional anisotropy and AD were increased in the three nigral subareas in PD (P < 0.01), but MD and RD were unaltered. The right SN had higher FA than the left in all subareas (P < 0.01). MD and AD were increased in the right anterior part (P < 0.04), whereas MD and RD were decreased in the right middle and posterior parts (P < 0.001). The left middle cerebellar peduncle had increased FA and AD (P < 0.001) and decreased MD and RD (P < 0.01) compared to the right. Diffusion measures did not progress over time and side differences were not related to disease or lateralization of symptoms. Conclusions: Increased FA in the SN in PD indicates gliosis and inflammation in the nuclei, but possibly also intrusion of surrounding fibres into the shrinking structure. The hemispheric side differences of diffusion might reflect natural lateralization of connectivity, but their relation to PD must be studied further.

  • 339.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Åström, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Jakobson Mo, Susanna
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Fractional Anisotropy and Mean Diffusion as Measures of Dopaminergic Function in Parkinson's Disease: Challenging Results2017Inngår i: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, nr 1, s. 129-142Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Diffusion tensor imaging (DTI) has been purported as an imaging technique to assess dopaminergic degeneration in Parkinson’s disease.

    Objective: To test if fractional anisotropy (FA) and mean diffusion (MD) in the basal ganglia as measured by DTI correlates with dopaminergic function as measured by dopamine transporter (DAT) and dopamine D2-receptor (D2R) SPECT.

    Methods: One-hundred and eleven patients with Parkinson’s disease (71±10 years) and thirty-one controls (68±7 years) performed DTI, DAT and D2R SPECT at baseline and four follow-ups (1-year: 89 patients/zero controls; 3-year: 72/11; 5-year: 48/17; and 8-year: 13/13). Four equipment combinations of MRI scanners/SPECT gamma cameras were used during the study. Data from each combination were analyzed separately. Regions-of-interest were outlined in the substantia nigra (three subareas, DTI only) and in the striatum (putamen and caudate). Side differences and bilateral averages were correlated using linear regression. The significance threshold was set at P < 0.001 and 0.001 < P< 0.05 was defined as a trend towards significance.

    Results: For side differences, no significant correlations were observed, but in patients, there was a trend towards a negative correlation between MD in the middle nigra and putaminal DAT uptake in two combinations (P = 0.04 and P = 0.03). For averages, in patients, striatal MD correlated negatively with striatal DAT uptake in one combination (P = 0.0005) and trended towards negative correlations with striatal D2R uptake (one combination, P = 0.03) and with the sum of striatal DAT and D2R uptake (two combinations P = 0.002 and P = 0.03). FA showed no correlations in patients, and no correlations were found in controls.

    Conclusions: The poor correlations between MD and dopamine activity –and absent correlations for FA – imply that additional diffusion measures must be developed to reliably assess the dopaminergic degeneration in Parkinson’s disease.

  • 340.
    Levinsson, Jennie
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Thrombectomy versus intravenous thrombolysis for the treatment of acute ischemic stroke.2015Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 341. Lill, Christina M.
    et al.
    Rengmark, Aina
    Pihlstrom, Lasse
    Fogh, Isabella
    Shatunov, Aleksey
    Sleiman, Patrick M.
    Wang, Li-San
    Liu, Tian
    Lassen, Christina F.
    Meissner, Esther
    Alexopoulos, Panos
    Calvo, Andrea
    Chio, Adriano
    Dizdar, Nil
    Faltraco, Frank
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Kirchheiner, Julia
    Kurz, Alexander
    Larsen, Jan P.
    Liebsch, Maria
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Morrison, Karen E.
    Nissbrandt, Hans
    Otto, Markus
    Pahnke, Jens
    Partch, Amanda
    Restagno, Gabriella
    Rujescu, Dan
    Schnack, Cathrin
    Shaw, Christopher E.
    Shaw, Pamela J.
    Tumani, Hayrettin
    Tysnes, Ole-Bjorn
    Valladares, Otto
    Silani, Vincenzo
    van den Berg, Leonard H.
    van Rheenen, Wouter
    Veldink, Jan H.
    Lindenberger, Ulman
    Steinhagen-Thiessen, Elisabeth
    Teipel, Stefan
    Perneczky, Robert
    Hakonarson, Hakon
    Hampel, Harald
    von Arnim, Christine A. F.
    Olsen, Jorgen H.
    Van Deerlin, Vivianna M.
    Al-Chalabi, Ammar
    Toft, Mathias
    Ritz, Beate
    Bertram, Lars
    The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease2015Inngår i: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, nr 12, s. 1407-1416Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2's role in AD may involve tau dysfunction. (C) 2015 The Alzheimer's Association.

  • 342.
    Lindberg, Gustaf
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Complications of lumbar discectomies – A retrospective cohort study. Pre-, per- and postoperative events during microdiscectomies and their correlation to failed back surgery syndrome (FBSS).2014Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 343.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Idiopathic parkinsonism: epidemiology and clinical characteristics of a population-based incidence cohort2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Idiopathic parkinsonism is a neurodegenerative syndrome of unknown cause and includes Parkinson’s disease (PD) and atypical parkinsonian disorders. The atypical parkinsonian disorders are: Multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). The incidence rates of these diseases in Sweden are largely unknown. The diagnosis of each disease relies mainly on clinical examination although several imaging and laboratory parameters may show changes. A diagnosis based on clinical examination is especially difficult early in the course of each disease; diagnosis is easier later on when disease-charactersistic signs have evolved and become more prominent. However, even in later stages it is not uncommon that patients are misdiagnosed. PD can be divided into subgroups based on the main clinical symptoms, i. e. tremor dominant, postural instability and gait difficulty (PIGD), and indeterminate. The PIGD subtype has worse prognosis including higher risk of dementia. The aims were to study the incidence of idiopathic parkinsonism and the different specific parkinsonian disorders in the Umeåregion and to investigate the patients early in the course of the disease with brainmagnetic resonance tomography (MRI), external anal sphincterelectromyography (EAS-EMG) and oculomotor examination. Can these methods improve the differential diagnostic work-up and/or differentiate between the subtypes of PD?

    Methods: We examined all patients in our catchment area (142,000 inhabitants) who were referred to us due to a suspected parkinsonian syndrome. Our clinic is the only clinic in the area receiving referrals regarding movement disorders. During the period (January 1, 2004 through April 30,2009) 190 patients fulfilled the inclusion criteria and were included in the study. Healthy volunteers served as controls. 

    Results: Incidence: We found the highest incidences reported in the literature: PD (22.5/100,000/year), MSA(2.4/100,000/year), and PSP (1.2/100,000/year). No CBD patients were encountered. Brain MRI: Degenerative changes were common both in controls and PD. There were no differences between the PD subtypes. EAS-EMG: Pathological changes in EAS-EMG examination were common in PD, MSA and PSP. It was not possible to separate PD, MSA and PSP by the EAS-EMG examination. Oculomotor examination: Pathological results were common in all diagnosis groups compared to controls. It was not possible to separate PD, MSA and PSP or the PD subtypes with the help of oculomotor examination.

    Conclusions: The incidences of idiopathic parkinsonism, PD, MSA and PSP were higher than previously reported in the literature. It is not clear weather this is due to a true higher incidence in the Umeå region or a more effective casefinding than in other studies. MRI, EAS-EMG and oculomotor examination could not contribute to the differential diagnostic work-up between PD, MSA and PSP nor differentiate between PD subtypes early in the course of the disease.

  • 344.
    Linder, Jan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Libelius, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nordh, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Holmberg, Björn
    Institute of Neuroscience and Physiology/Neurology Göteborg University, Göteborg, Sweden..
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Anal sphincter electromyography in patients with newly diagnosed idiopathic parkinsonism2012Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 126, nr 4, s. 248-255Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives The differential diagnosis of patients with idiopathic parkinsonism is difficult, especially early in the course of the disease. External anal sphincter electromyography has been reported to be of value in the differential diagnosis between Parkinson’s disease and multiple system atrophy. Patients with multiple system atrophy are reported to have pathological external anal sphincter electromyography and patients with Parkinson’s disease are reported to have significantly less pathological external anal sphincter electromyography results. Comparisons between patients with parkinsonian disorders have usually been made many years into the disease, and thus it is largely unknown if the results of external anal sphincter electromyography can be used to distinguish the different diagnoses in the early phase of the disease.

    Material and methods We investigated 148 newly diagnosed patients with idiopathic parkinsonism from a population-based incidence cohort (100 definite Parkinson’s disease, 21 probable Parkinson’s disease, 16 multiple system atrophy, eleven progressive supranuclear palsy, and 40 controls) with external anal sphincter electromyography within three months of their first visit and, in the majority of patients, before start of treatment with dopaminergic drugs. The clinical diagnoses were made using established clinical diagnostic criteria after a median follow-up of three years.

    Results All patient groups had more pathological external anal sphincter electromyography results than controls. No external anal sphincter electromyography differences were found between the patient groups, especially not between Parkinson’s disease and multiple system atrophy.

    Conclusions External anal sphincter electromyography examination cannot separate the different parkinsonian subgroups from each other in early course of the diseases.

  • 345.
    Lindgren, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindvall, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nilsson, Leif
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Naredi, Silvana
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Cortisol levels are influenced by sedation in the acute phase after subarachnoid haemorrhage2013Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, nr 4, s. 452-460Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Subarachnoid haemorrhage (SAH) is a life-threatening condition that may be aggravated by acute pituitary damage and cortisol insufficiency. Robust diagnostic criteria for critical illness-related corticosteroid insufficiency (CIRCI) are lacking. The aim of this study was to assess the frequency of CIRCI in the acute phase (0-240 h) after SAH and to evaluate associations between cortisol levels and clinical parameters (sedation, circulatory failure, gender, age, severity of disease, treatment). CIRCI was defined as a single morning serum cortisol (mSC) < 200 nmol/L. The lower limit for calculated free cortisol (cFC) was set at < 22 nmol/L, and for saliva cortisol at < 7.7 nmol/L.

    METHODS: Fifty patients were included. Serum/saliva cortisol and corticosteroid-binding globulin were obtained every second morning. A logistic regression model was used for multivariate analysis comparing cortisol levels with clinical parameters.

    RESULTS: Of the patients, 21/50 (42%) had an mSC < 200 nmol/L and 30/50 (60%) had a cFC < 22 nmol/L. In patients with continuous intravenous sedation, the odds ratio for a mSC to be < 200 nmol/L was 18 times higher (95% confidence interval 4.2-85.0, P < 0.001), and the odds ratio for a cFC to be < 22 nmol/L was 2.4 times higher (95% confidence interval 1.2-4.7, P < 0.05) compared with patients with no continuous intravenous sedation.

    CONCLUSIONS: Continuous intravenous sedation was significantly associated with cortisol values under defined limits (mSC < 200, cFC < 22 nmol/L). The possibility that sedating drugs per se may influence cortisol levels should be taken into consideration before CIRCI is diagnosed.

  • 346.
    Lindgren, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Hultin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lindvall, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Borota, Ljubisa
    Department of Radiology, Oncology and Radiation Science, Uppsala University, Sweden .
    Naredi, Silvana
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    ADMA levels and arginine/ADMA ratios reflect severity of disease and extent of inflammation after subarachnoid hemorraghe2014Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 21, nr 1, s. 91-101Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Subarachnoid hemorrhage (SAH) is characterized by an inflammatory response that might induce endothelial dysfunction. The aim of this study was to evaluate if ADMA and arginine/ADMA ratios after SAH (indicators of endothelial dysfunction) are related to clinical parameters, inflammatory response, and outcome.

    Methods: Prospective observational study. ADMA, arginine, C-reactive protein (CRP), and cytokines were obtained 0–240 h (h) after SAH. Definition of severe clinical condition was Hunt&Hess (H&H) 3–5 and less severe clinical condition H&H 1–2. Impaired cerebral circulation was assessed by clinical examination, transcranial doppler, CT-scan, and angiography. Glasgow outcome scale (GOS) evaluated the outcome.

    Results: Compared to admission, 0–48 h after SAH, the following was observed 49–240 h after SAH; (a) ADMA was significantly increased at 97–240 h (highest 217–240 h), (b) CRP was significantly increased at 49–240 h (highest 73–96 h), (c) interleukin-6 (IL-6) was significantly lower at 97–240 h (highest 49–96 h), p < 0.05. ADMA, CRP, and IL-6 were significantly lower and peak arginine/ADMA ratio was significantly higher in patients with H&H 1–2 compared to patients with H&H 3–5, p < 0.05. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with (55 %) or without (45 %) signs of impaired cerebral circulation. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with GOS 1–3 and patients with GOS 4–5.

    Conclusions: ADMA increased significantly after SAH, and the increase in ADMA started after the pro-inflammatory markers (CRP and IL-6) had peaked. This might indicate that endothelial dysfunction, with ADMA as a marker, is induced by a systemic inflammation.

  • 347.
    Lindgren, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Hultin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Edvardsson, Ludwig
    Naredi, Silvana
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård. Göteborgs universitet.
    Long term survivors of subarachnoid haemorrhage have an increased risk of death due to cerebrovascular causesManuskript (preprint) (Annet vitenskapelig)
  • 348.
    Lindgren, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ssozi, Rashida
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Naredi, Silvana
    Cerebrospinal fluid lactate and neurological outcome after subarachnoid haemorrhage.2018Inngår i: Journal of clinical neuroscience, ISSN 0967-5868, E-ISSN 1532-2653, artikkel-id S0967-5868(18)30807-5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Increased lactate in cerebrospinal fluid (CSF) has been regarded as a marker for cerebral ischemia and damage in the central nervous system. The aim of this study was to evaluate if CSF-lactate was associated with; impaired cerebral circulation, outcome, sex, age, clinical condition or treatment after subarachnoid haemorrhage (SAH).

    METHODS: This study consists of 33 patients (22 females, 11 males) with aneurysmal SAH treated at Umeå university hospital 2008-2009. Samples were obtained from external ventricular catheters 0-240 h after SAH. Normal CFS-lactate was defined as 1.2-2-1 mmol/L. Hunt & Hess scale assessed clinical condition. Impaired cerebral circulation was evaluated by clinical examination, transcranial doppler, CT-scan, and cerebral angiography. Glasgow outcome scale (GOS) evaluated outcome.

    RESULTS: Seventy-nine CSF-lactate samples were analysed. CSF-lactate >2.1 mmol/L was found in 25/33 (76%) patients and in 50/79 (63%) samples. No difference in CSF-lactate levels was found over time. No association was found between patients with CSF-lactate >2.1 mmol/L and; sex, severity of clinical condition, impaired cerebral circulation or outcome. CSF-lactate >2.1 mmol/L was more common in patients ≥61 years of age (p = 0.04) and in patients treated with endovascular coiling compared to surgical clipping (p = 0.0001).

    CONCLUSION: In patients with SAH, no association was found between increased CSF-lactate (>2.1 mmol/L) and severe clinical condition, impaired cerebral circulation or unfavourable outcome. Endovascular coiling and age ≥61 years was associated with CSF-lactate above >2.1 mmol/L.

  • 349.
    Lindgren, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Naredi, Silvana
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hultin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Leptin levels after subarachnoid haemorrhage are gender dependent2016Inngår i: SpringerPlus, E-ISSN 2193-1801, Vol. 5, artikkel-id 667Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Subarachnoid hemorrhage (SAH) is a neurological disease where the majority of the patients are critically ill. The adipokine leptin has in cerebral emergencies been related to severity of disease and to adverse outcome. The aim of this study was to examine leptin levels over time after SAH and associations to gender, age, body mass index, severity of disease, parenteral lipids, systemic organ failure and outcome.

    Methods: Prospective observational study in 56 patients. Leptin was obtained 0-240 h after SAH, in 48 h intervals. Severity of disease was assessed with the Hunt and Hess score, organ failure with the sequential organ failure assessment score, and outcome with Glasgow outcome scale. Leptin levels in the SAH group were compared with controls from the same geographical area.

    Results: At admission, Leptin was significantly higher in SAH patients compared to controls, both in female (28.6 +/- 25.6 vs 13.0 +/- 2.3 ng/mL, p = 0.001) and male patients (13.3 +/- 8.4 vs 4.3 +/- 0.7 ng/mL, p = 0.001). Leptin levels remained stable over time. Female patients had significantly higher leptin levels than male patients, and deceased female patients had higher leptin levels than female survivors (85.5 +/- 20.5 vs 50.5 +/- 34.6, n = 4/35, p < 0.05). Leptin levels did not differ between male survivors and non-survivors. Leptin levels were not associated with severity of disease, organ failure or parenteral lipids.

    Conclusion: Leptin levels were significantly higher in both male and female patients compared to controls. Higher leptin levels were related to outcome and organ failure in women but not in men. When analysing leptin levels gender-related differences should be considered.

  • 350.
    Lindgren, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Nordh, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Naredi, Silvana
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Olivecrona, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Frequency of non-convulsive Seizures and non-convulsive status Epilepticus in Subarachnoid Hemorrhage patients in need of controlled ventilation and sedation2012Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 17, nr 3, s. 367-373Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Non-convulsive seizures (NCSZ) can be more prevalent than previously recognized among comatose neuro-intensive care patients. The aim of this study was to evaluate the frequency of NCSZ and non-convulsive status epilepticus (NCSE) in sedated and ventilated subarachnoid hemorrhage (SAH) patients.

    METHODS: Retrospective study at a university hospital neuro-intensive care unit, from January 2008 until June 2010. Patients were treated according to a local protocol, and were initially sedated with midazolam or propofol or combinations of these sedative agents. Thiopental was added for treatment of intracranial hypertension. No wake-up tests were performed. Using NicoletOne((R)) equipment (VIASYS Healthcare Inc., USA), continuous EEG recordings based on four electrodes and a reference electrode was inspected at full length both in a two electrode bipolar and a four-channel referential montage.

    RESULTS: Approximately 5,500 h of continuous EEG were registered in 28 SAH patients (33 % of the patients eligible for inclusion). The median Glasgow Coma scale was 8 (range 3-14) and the median Hunt and Hess score was 4 (range 1-4). During EEG registration, no clinical seizures were observed. In none of the patients inter ictal epileptiform activity was seen. EEG seizures were recorded only in 2/28 (7 %) patients. One of the patients experienced 4 min of an NCSZ and one had a 5 h episode of an NCSE.

    CONCLUSION: Continuous EEG monitoring is important in detecting NCSZ in sedated patients. Continuous sedation, without wake-up tests, was associated with a low frequency of subclinical seizures in SAH patients in need of controlled ventilation.

45678910 301 - 350 of 629
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf