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  • 1.
    Abdollahi, Nyayesh
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Modifierad constraint-induced movement therapy förbättrar livskvalitet hos unga stroke-patienter2015Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 2. Abel, Olubunmi
    et al.
    Powell, John F.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Al-Chalabi, Ammar
    ALSoD: A user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics2012Inngår i: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 33, nr 9, 1345-1351 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is the commonest adult onset motor neuron disease, with a peak age of onset in the seventh decade. With advances in genetic technology, there is an enormous increase in the volume of genetic data produced, and a corresponding need for storage, analysis, and interpretation, particularly as our understanding of the relationships between genotype and phenotype mature. Here, we present a system to enable this in the form of the ALS Online Database (ALSoD at http://alsod.iop.kcl.ac.uk), a freely available database that has been transformed from a single gene storage facility recording mutations in the SOD1 gene to a multigene ALS bioinformatics repository and analytical instrument combining genotype, phenotype, and geographical information with associated analysis tools. These include a comparison tool to evaluate genes side by side or jointly with user configurable features, a pathogenicity prediction tool using a combination of computational approaches to distinguish variants with nonfunctional characteristics from disease-associated mutations with more dangerous consequences, and a credibility tool to enable ALS researchers to objectively assess the evidence for gene causation in ALS. Furthermore, integration of external tools, systems for feedback, annotation by users, and two-way links to collaborators hosting complementary databases further enhance the functionality of ALSoD. Hum Mutat 33:1345-1351, 2012. (c) 2012 Wiley Periodicals, Inc.

  • 3. Abel, Olubunmi
    et al.
    Powell, John F
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Al-Chalabi, Ammar
    Credibility analysis of putative disease-causing genes using bioinformatics2013Inngår i: PLoS ONE, ISSN 1932-6203, Vol. 8, nr 6, e64899- s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Genetic studies are challenging in many complex diseases, particularly those with limited diagnostic certainty, low prevalence or of old age. The result is that genes may be reported as disease-causing with varying levels of evidence, and in some cases, the data may be so limited as to be indistinguishable from chance findings. When there are large numbers of such genes, an objective method for ranking the evidence is useful. Using the neurodegenerative and complex disease amyotrophic lateral sclerosis (ALS) as a model, and the disease-specific database ALSoD, the objective is to develop a method using publicly available data to generate a credibility score for putative disease-causing genes.

    Methods: Genes with at least one publication suggesting involvement in adult onset familial ALS were collated following an exhaustive literature search. SQL was used to generate a score by extracting information from the publications and combined with a pathogenicity analysis using bioinformatics tools. The resulting score allowed us to rank genes in order of credibility. To validate the method, we compared the objective ranking with a rank generated by ALS genetics experts. Spearman's Rho was used to compare rankings generated by the different methods.

    Results: The automated method ranked ALS genes in the following order: SOD1, TARDBP, FUS, ANG, SPG11, NEFH, OPTN, ALS2, SETX, FIG4, VAPB, DCTN1, TAF15, VCP, DAO. This compared very well to the ranking of ALS genetics experts, with Spearman's Rho of 0.69 (P = 0.009).

    Conclusion: We have presented an automated method for scoring the level of evidence for a gene being disease-causing. In developing the method we have used the model disease ALS, but it could equally be applied to any disease in which there is genotypic uncertainty.

  • 4. Abosch, Aviva
    et al.
    Timmermann, Lars
    Bartley, Sylvia
    Rietkerk, Hans Guido
    Whiting, Donald
    Connolly, Patrick J.
    Lanctin, David
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    An International Survey of Deep Brain Stimulation Procedural Steps2013Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 91, nr 1, 1-11 s.Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Background: Deep brain stimulation (DBS) surgery is standard of care for the treatment of certain movement disorders.

    Objective: We sought to characterize the spectrum of steps performed in DBS surgery, at centers around the world where this surgery is performed.

    Methods: We identified the main steps in DBS surgery workflow and grouped these 19 steps into 3 phases (preoperative, operative, and postoperative). A survey tool, informed by a pilot survey, was administered internationally by trained study personnel at high- and low-volume DBS centers. Procedural components, duration, and surgeon motivational factors were assessed. Cluster analysis was used to identify procedural and behavioral clusters.

    Results: One hundred eighty-five procedure workflow surveys (143 DBS centers) and 65 online surveys of surgeon motivational drivers were completed (45% response rate). Significant heterogeneity in technique, operative time, and surgeon motivational drivers was reported across centers.

    Conclusions: We provide a description of the procedural steps involved in DBS surgery and the duration of these steps, based on an international survey. These data will enable individual surgeons and centers to examine their own experience relative to colleagues at other centers and in other countries. Such information could also be useful in comparing efficiencies and identifying workflow obstacles between different hospital environments.

  • 5.
    Akimoto, Chizuru
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linder, Jan
    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.
    Backlund, Irene
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Andersson, Jörgen
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nilsson, Ann-Charloth
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Alstermark, Helena
    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.
    No GGGGCC-hexanucleotide repeat expansion in C9ORF72 in parkinsonism patients in Sweden2013Inngår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, Vol. 14, nr 1, 26-29 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An intronic GGGGCC-hexanucleotide repeat expansion in C9ORF72 was recently identified as a major cause of amyotrophic lateral sclerosis and frontotemporal dementia. Some amyotrophic lateral sclerosis patients have signs of parkinsonism, and many parkinsonism patients develop dementia. In this study we examined if the hexanucleotide repeat expansion was present in parkinsonism patients, to clarify if there could be a relationship between the repeat expansion and disease. We studied the size of the hexanucleotide repeat expansion in a well defined population-based cohort of 135 Parkinson's disease patients and 39 patients with atypical parkinsonism and compared with 645 Swedish control subjects. We found no correlation between Parkinson's disease or atypical parkinsonism and the size of the GGGGCC repeat expansion in C9ORF72. In conclusion, this GGGGCC-repeat expansion in C9ORF72 is not a cause of parkinsonism in the Swedish population.

  • 6.
    Akimoto, Chizuru
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Volk, Alexander E.
    van Blitterswijk, Marka
    Van den Broeck, Marleen
    Leblond, Claire S.
    Lumbroso, Serge
    Camu, William
    Neitzel, Birgit
    Onodera, Osamu
    van Rheenen, Wouter
    Pinto, Susana
    Weber, Markus
    Smith, Bradley
    Proven, Melanie
    Talbot, Kevin
    Keagle, Pamela
    Chesi, Alessandra
    Ratti, Antonia
    van der Zee, Julie
    Alstermark, Helena
    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.
    Calini, Daniela
    Nordin, Angelica
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Tradowsky, Daniela C.
    Just, Walter
    Daoud, Hussein
    Angerbauer, Sabrina
    DeJesus-Hernandez, Mariely
    Konno, Takuya
    Lloyd-Jani, Anjali
    de Carvalho, Mamede
    Mouzat, Kevin
    Landers, John E.
    Veldink, Jan H.
    Silani, Vincenzo
    Gitler, Aaron D.
    Shaw, Christopher E.
    Rouleau, Guy A.
    van den Berg, Leonard H.
    Van Broeckhoven, Christine
    Rademakers, Rosa
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Kubisch, Christian
    A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories2014Inngår i: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 51, nr 6, 419-424 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9-100%), and the mean specificity was 98.0% (87.5-100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.

  • 7. Akram, Harith
    et al.
    Limousin, Patricia
    Hyam, Jonathan
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London.
    Zrinzo, Ludvic
    Aim for the Suprasternal Notch: Technical Note to Avoid Bowstringing after Deep Brain Stimulation2015Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 93, nr 4, 227-230 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Bowstringing may occur when excessive fibrosis develops around extension cables in the neck after deep brain stimulation (DBS) surgery. Though the occurrence of this phenomenon is rare, we have noted that it tends to cause maximal discomfort when the cables cross superficially over the convexity of the clavicle. We hypothesise that bowstringing may be avoided by directing the extension cables towards the suprasternal notch. Methods: When connecting DBS leads to an infraclavicular pectoral implantable pulse generator (IPG), tunnelling is directed towards the suprasternal I notch, before being directed laterally towards the IPG pocket. In previously operated patients with established fibrosis, the fibrous tunnel is opened and excised as far cranially as possible, allowing medial rerouting of cables. Using this approach, we reviewed our series of patients who underwent DBS surgery over 10 years. Results: In 429 patients, 7 patients (2%) with cables tunnelled over the convexity of the clavicle complaining of bowstringing underwent cable exploration and rerouting. This eliminated bowstringing and provided better cosmetic results. When the cable trajectory was initially directed towards the suprasternal notch, no bowstringing was observed. Conclusion:The tunnelling trajectory appears to influence postoperative incidence of fibrosis associated with DBS cables. Modifying the surgical technique may reduce the incidence of this troublesome adverse event. (C) 2015 S.Karger AG, Basel

  • 8. Akram, Harith
    et al.
    Sotiropoulos, Stamatios N.
    Jbabdi, Saad
    Georgiev, Dejan
    Mahlknecht, Philipp
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Jahanshahi, Marjan
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
    Ashburner, John
    Behrens, Tim
    Zrinzo, Ludvic
    Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson's disease2017Inngår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 158, 332-345 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.

    Methods: High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.

    Results: All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H-2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -3(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.

    Interpretation: These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.

  • 9. Akram, Harith
    et al.
    Wu, Chengyuan
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Yousry, Tarek
    Jahanshahi, Marjan
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK.
    Behrens, Timothy
    Ashburner, John
    Zrinzo, Ludvic
    L-Dopa Responsiveness Is Associated With Distinctive Connectivity Patterns in Advanced Parkinson's Disease2017Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, nr 6, 874-883 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. Methods: To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to L-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3x3x2.5mm(3) voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an L-dopa challenge. False discovery rate-corrected P was set at < 0.05 for a 2-tailed t test. Results: A greater improvement in UPDRS-III scores following L-dopa administration was characterized by higher resting-state functional connectivity between the prefrontal cortex and the striatum (P=0.001) and lower resting-state functional connectivity between the pallidum (P=0.001), subthalamic nucleus (P=0.003), and the paracentral lobule (supplementary motor area, mesial primary motor, and primary sensory areas). Conclusions: Our findings show characteristic basal ganglia resting-state functional connectivity patterns associated with different degrees of L-dopa responsiveness in patients with advanced Parkinson's disease. L-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response.

  • 10. Al Nimer, Faiez
    et al.
    Elliott, Christina
    Bergman, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Khademi, Mohsen
    Dring, Ann M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Aeinehband, Shahin
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Christensen, Jeppe Romme
    Sellebjerg, Finn
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linington, Christopher
    Olsson, Tomas
    Piehl, Fredrik
    Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination2016Inngår i: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 3, nr 1, e191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: We aimed to examine the regulation of lipocalin-2 (LCN2) in multiple sclerosis (MS) and its potential functional relevance with regard to myelination and neurodegeneration. Methods: We determined LCN2 levels in 3 different studies: (1) in CSF and plasma from a case-control study comparing patients with MS (n = 147) with controls (n = 50) and patients with relapsing-remitting MS (n = 75) with patients with progressive MS (n = 72); (2) in CSF and brain tissue microdialysates from a case series of 7 patients with progressive MS; and (3) in CSF at baseline and 60 weeks after natalizumab treatment in a cohort study of 17 patients with progressive MS. Correlation to neurofilament light, a marker of neuroaxonal injury, was tested. The effect of LCN2 on myelination and neurodegeneration was studied in a rat in vitro neuroglial cell coculture model. Results: Intrathecal production of LCN2 was increased predominantly in patients with progressive MS (p < 0.005 vs relapsing-remitting MS) and displayed a positive correlation to neurofilament light (p = 0.005). Levels of LCN2 in brain microdialysates were severalfold higher than in the CSF, suggesting local production in progressive MS. Treatment with natalizumab in progressive MS reduced LCN2 levels an average of 13% (p < 0.0001). LCN2 was found to inhibit remyelination in a dose-dependent manner in vitro. Conclusions: LCN2 production is predominantly increased in progressive MS. Although this moderate increase does not support the use of LCN2 as a biomarker, the correlation to neurofilament light and the inhibitory effect on remyelination suggest that LCN2 might contribute to neurodegeneration through myelination-dependent pathways.

  • 11. Al Nimer, Faiez
    et al.
    Thelin, Eric
    Nystrom, Harriet
    Dring, Ann M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Piehl, Fredrik
    Nelson, David W.
    Bellander, Bo-Michael
    Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 7, e0132177Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L) has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s-) and cerebrospinal fluid (CSF-) NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI). A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE). CSF-NF-L was measured in a subcohort (n = 84) with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT) and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5). In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R-2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R-2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B), S-NF-L yielded an extra 0.023 pseudo-R-2 and a significantly better model (p = 0.006) No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that SNF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further

  • 12. Alping, P.
    et al.
    Svenningsson, A.
    Clinical Science Danderyd´s Hospital, Karolinska Institutet, Stockholm.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Burman, J.
    Dahle, C.
    Fink, K.
    Hillert, J.
    Lycke, J.
    Landtblom, A. -M
    Martin, C.
    Nilsson, P.
    Walentin, F.
    Olsson, T.
    Frisell, T.
    Piehl, F.
    Rituximab in multiple sclerosis: data from the swedish MS registry2016Inngår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, 49-49 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 13. Alping, Peter
    et al.
    Frisell, Thomas
    Novakova, Lenka
    Islam-Jakobsson, Protik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Björck, Anna
    Axelsson, Markus
    Malmeström, Clas
    Fink, Katharina
    Lycke, Jan
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Rituximab versus Fingolimod after Natalizumab in Multiple Sclerosis Patients2016Inngår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 79, nr 6, 950-958 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Many JC virus antibody-positive relapsing-remitting multiple sclerosis (RRMS) patients who are stable on natalizumab switch to other therapies to avoid progressive multifocal leukoencephalopathy.

    Methods: We compared outcomes for all RRMS patients switching from natalizumab due to JC virus antibody positivity at 3 Swedish multiple sclerosis centers with different preferential use of rituximab and fingolimod (Stockholm, n = 156, fingolimod 51%; Gothenburg, n = 64, fingolimod 88%; Umea, n = 36, fingolimod 19%), yielding a total cohort of N = 256 (fingolimod 55%).

    Results: Within 1.5 years of cessation of natalizumab, 1.8% (rituximab) and 17.6% (fingolimod) of patients experienced a clinical relapse (hazard ratio for rituximab = 0.10, 95% confidence interval [CI] = 0.02-0.43). The hazard ratio (favoring rituximab) for adverse events (5.3% vs 21.1%) and treatment discontinuation (1.8% vs 28.2%) were 0.25 (95% CI = 0.10-0.59) and 0.07 (95% CI = 0.02-0.30), respectively. Furthermore, contrast-enhancing lesions were found in 1.4% (rituximab) versus 24.2% (fingolimod) of magnetic resonance imaging examinations (odds ratio = 0.05, 95% CI = 0.00-0.22). Differences remained when adjusting for possible confounders (age, sex, disability status, time on natalizumab, washout time, follow-up time, and study center).

    Interpretation: Our findings suggest an improved effectiveness and tolerability of rituximab compared with fingolimod in stable RRMS patients who switch from natalizumab due to JC virus antibody positivity. Although residual confounding factors cannot be ruled out, the shared reason for switching from natalizumab and the preferential use of either rituximab or fingolimod in 2 of the centers mitigates these concerns.

  • 14.
    Ambarki, Khalid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hallberg, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Lindén, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Zarrinkoob, Laleh
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Blood flow of ophthalmic artery in healthy individuals determined by phase-contrast magnetic resonance imaging2013Inngår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, Vol. 54, nr 4, 2738-2745 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Recent development of magnetic resonance imaging (MRI) offers new possibilities to assess ocular blood flow. This prospective study evaluates the feasibility of phase-contrast MRI (PCMRI) to measure flow rate in the ophthalmic artery (OA) and establish reference values in healthy young (HY) and elderly (HE) subjects.

    METHODS: Fifty HY subjects (28 females, 21-30 years of age) and 44 HE (23 females, 64-80 years of age) were scanned on a 3-Tesla MR system. The PCMRI sequence had a spatial resolution of 0.35 mm per pixel, with the measurement plan placed perpendicularly to the OA. Mean flow rate (Qmean), resistive index (RI), and arterial volume pulsatility of OA (ΔVmax) were measured from the flow rate curve. Accuracy of PCMRI measures was investigated using a vessel-phantom mimicking the diameter and the flow rate range of the human OA.

    RESULTS: Flow rate could be assessed in 97% of the OAs. Phantom investigations showed good agreement between the reference and PCMRI measurements with an error of <7%. No statistical difference was found in Qmean between HY and HE individuals (HY: mean ± SD = 10.37 ± 4.45 mL/min; HE: 10.81 ± 5.15 mL/min, P = 0.655). The mean of ΔVmax (HY: 18.70 ± 7.24 μL; HE: 26.27 ± 12.59 μL, P < 0.001) and RI (HY: 0.62 ± 0.08; HE: 0.67 ± 0.1, P = 0.012) were significantly different between HY and HE.

    CONCLUSIONS: This study demonstrated that the flow rate of OA can be quantified using PCMRI. There was an age difference in the pulsatility parameters; however, the mean flow rate appeared independent of age. The primary difference in flow curves between HE and HY was in the relaxation phase of the systolic peak.

  • 15.
    Ambarki, Khalid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Lindqvist, Tomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Petterson, E
    Warntjes, JBM
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Evaluation of automatic measurement of the intracranial volume based on quantitative MR imaging2012Inngår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 33, nr 10, 1951-1956 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE: Brain size is commonly described in relation to ICV, whereby accurate assessment of this quantity is fundamental. Recently, an optimized MR sequence (QRAPMASTER) was developed for simultaneous quantification of T1, T2, and proton density. ICV can be measured automatically within minutes from QRAPMASTER outputs and a dedicated software, SyMRI. Automatic estimations of ICV were evaluated against the manual segmentation.

    MATERIALS AND METHODS: In 19 healthy subjects, manual segmentation of ICV was performed by 2 neuroradiologists (Obs1, Obs2) by using QBrain software and conventional T2-weighted images. The automatic segmentation from the QRAPMASTER output was performed by using SyMRI. Manual corrections of the automatic segmentation were performed (corrected-automatic) by Obs1 and Obs2, who were blinded from each other. Finally, the repeatability of the automatic method was evaluated in 6 additional healthy subjects, each having 6 repeated QRAPMASTER scans. The time required to measure ICV was recorded.

    RESULTS: No significant difference was found between reference and automatic (and corrected-automatic) ICV (P > .25). The mean difference between the reference and automatic measurement was -4.84 ± 19.57 mL (or 0.31 ± 1.35%). Mean differences between the reference and the corrected-automatic measurements were -0.47 ± 17.95 mL (-0.01 ± 1.24%) and -1.26 ± 17.68 mL (-0.06 ± 1.22%) for Obs1 and Obs2, respectively. The repeatability errors of the automatic and the corrected-automatic method were <1%. The automatic method required 1 minute 11 seconds (SD = 12 seconds) of processing. Adding manual corrections required another 1 minute 32 seconds (SD = 38 seconds).

    CONCLUSIONS: Automatic and corrected-automatic quantification of ICV showed good agreement with the reference method. SyMRI software provided a fast and reproducible measure of ICV.

  • 16.
    Ambarki, Khalid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wåhlin, Anders
    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.
    MR imaging of brain volumes: evaluation of a fully automatic software2011Inngår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 32, nr 2, 408-412 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE: Automatic assessment of brain volumes is needed in researchand clinical practice. Manual tracing is still the criterionstandard but is time-consuming. It is important to validatethe automatic tools to avoid the problems of clinical studiesdrawing conclusions on the basis of brain volumes estimatedwith methodologic errors. The objective of this study was toevaluate a new commercially available fully automatic softwarefor MR imaging of brain volume assessment. Automatic and expertmanual brain volumes were compared.

    MATERIALS AND METHODS: MR imaging (3T, axial T2 and FLAIR) was performed in 41 healthyelderly volunteers (mean age, 70 ± 6 years) and 20 patientswith hydrocephalus (mean age, 73 ± 7 years). The softwareQBrain was used to manually and automatically measure the followingbrain volumes: ICV, BTV, VV, and WMHV. The manual method hasbeen previously validated and was used as the reference. Agreementbetween the manual and automatic methods was evaluated by usinglinear regression and Bland-Altman plots.

    RESULTS: There were significant differences between the automatic andmanual methods regarding all volumes. The mean differences wereICV = 49 ± 93 mL (mean ± 2SD, n = 61), BTV = 11± 70 mL, VV = –6 ± 10 mL, and WMHV = 2.4± 9 mL. The automatic calculations of brain volumes tookapproximately 2 minutes per investigation.

    CONCLUSIONS: The automatic tool is promising and provides rapid assessmentof brain volumes. However, the software needs improvement beforeit is incorporated into research or daily use. Manual segmentationremains the reference method.

  • 17.
    Ambarki, Khalid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Zarrinkoob, Laleh
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wirestam, R.
    Petr, J.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Accuracy of Parenchymal Cerebral Blood Flow Measurements Using Pseudocontinuous Arterial Spin-Labeling in Healthy Volunteers2015Inngår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 36, nr 10, 1816-1821 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE: The arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method. MATERIALS AND METHODS: Ninety-two healthy volunteers were included: 49 young (age range, 20-30 years) and 43 elderly (age range, 65-80 years). Arterial spin-labeling parenchymal CBF values were averaged over the whole brain to quantify the mean pCBF(ASL) value. Total. CBF was assessed with phase-contrast MR imaging as the sum of flows in the internal carotid and vertebral arteries, and subsequent division by brain volume returned the pCBF(PCMRI) value. Accuracy was considered as good as that of the reference method if the systematic difference was less than 5 mL/min/100 g of brain tissue and if the 95% confidence intervals were equal to or better than +/- 10 mL/min/100 g. RESULTS: pCBF(ASL) correlated to pCBF(PCMRI) (r = 0.73; P < .001). Significant differences were observed between the pCBF(ASL) and pCBF(PCMRI) values in the young (P = .001) and the elderly (P < .001) volunteers. The systematic differences (mean 2 standard deviations) were -4 +/- 14 mL/min/100 g in the young subjects and 6 +/- 12 mL/min/100 g in the elderly subjects. Young subjects showed higher values than the elderly subjects for pCBF(PCMRI) (young, 57 +/- 8 mL/min/100 g; elderly, 54 +/- 7 mL/min/100 g; P = .05) and pCBF(ASL) (young, 61 +/- 10 mL/min/100 g; elderly, 48 +/- 10 mL/min/100 g; P < .001). CONCLUSIONS: The limits of agreement were too wide for the arterial spin-labeling method to be considered satisfactorily accurate, whereas the systematic overestimation in the young subjects and underestimation in the elderly subjects were close to acceptable. The age-related decrease in parenchymal CBF was augmented in arterial spin-labeling compared with phase-contrast MR imaging.

  • 18.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    ALS and FTD: two sides of the same coin?2013Inngår i: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 12, nr 10, 937-938 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 19.
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Mutation in C9orf72 changes the boundaries of ALS and FTD2012Inngår i: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 11, nr 3, 205-207 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 20.
    Andersson, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Prevalence of idiopathic normal pressure hydrocephalus. A pilot study in Jämtland.2015Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 21.
    Andersson, Kennet
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Manchester, I. R.
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Cesarini, K. Giuliana
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Measurement of CSF dynamics with oscillating pressure infusion2013Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 128, nr 1, 17-23 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction Infusion tests are used to diagnose and select patients with idiopathic normal pressure hydrocephalus (INPH) for shunt surgery. The test characterizes cerebrospinal fluid dynamics and estimates parameters of the cerebrospinal fluid system, the pressure-volume index (PVI) and the outflow conductance (Cout). The Oscillating Pressure Infusion (OPI) method was developed to improve the test and reduce the investigation time. The aim of this study was to evaluate the new OPI method by comparing it with an established reference method. Methods Forty-seven patients (age 71.2 +/- 8.9years) with communicating hydrocephalus underwent a preoperative lumbar infusion investigation with two consecutive infusion protocols, reference (42min) and new (20min), that is, 94 infusion tests in total. The OPI method estimated Cout and PVI simultaneously. A real-time analysis of reliability was applied to investigate the possibility of infusion time reduction. Results The difference in Cout between the methods was 1.2 +/- 1.8l/s/kPa (Rout=-0.8 +/- 3.5mmHg/ml/min), P<0.05, n=47. With the reliability analysis, the preset 20min of active infusion could have been even further reduced for 19 patients to between 10 and 19min. PVI was estimated to 16.1 +/- 6.9ml, n=47. Conclusions The novel Oscillating Pressure Infusion method produced real-time estimates of Cout including estimates of reliability that was in good agreement with the reference method and allows for a reduced and individualized investigation time.

  • 22.
    Andersson, Kennet
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Effect of resting pressure on the estimate of cerebrospinal fluid outflow conductance2011Inngår i: Fluids and barriers of the CNS, ISSN 2045-8118, Vol. 8, nr 1, 15- s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: A lumbar infusion test is commonly used as a predictive test for patients with normal pressure hydrocephalus and for evaluation of cerebrospinal fluid (CSF) shunt function. Different infusion protocols can be used to estimate the outflow conductance (Cout) or its reciprocal the outflow resistance, (Rout) with or without using the baseline resting pressure, Pr. Both from a basic physiological research and a clinical perspective, it is important to understand the limitations of the model on which infusion tests are based. By estimating Cout using two different analyses, with or without Pr, the limitations could be explored. The aim of this study was to compare the Cout estimates, and investigate what effect Pr had on the results.

    METHODS: Sixty-three patients that underwent a constant pressure infusion protocol as part of their preoperative evaluation for normal pressure hydrocephalus, were included (age 70.3+/-10.8 years (mean +/-SD). The analysis was performed without (Cexcl Pr) and with (Cincl Pr) Pr. The estimates were compared using Bland-Altman plots and paired sample t-tests (p<0.05 considered significant).

    RESULTS: Mean Cout for the 63 patients was: Cexcl Pr = 7.0+/-4.0 (mean +/-SD) ul/(s kPa) and Cincl Pr = 9.1+/-4.3 ul/(s kPa) and Rout was 19.0+/-9.2 and 17.7+/-11.3 mmHg/ml/min, respectively. There was a positive correlation between methods (r=0.79, n=63, p<0.01). The difference, DeltaCout, -2.1+/-2.7 ul/(s kPa) between methods was significant (p<0.01) and DeltaRout was 1.2 +/- 8.8 mmHg/ml/min). The Bland-Altman plot visualized that the variation around the mean difference was similar all through the range of measured values and there was no correlation between DeltaCout and Cout.

    CONCLUSIONS: The difference between Cout estimates, obtained from analyses with or without Pr, needs to be taken into consideration when comparing results from studies using different infusion test protocols. The study suggests variation in CSF formation rate, variation in venous pressure or a pressure dependent Cout as possible causes for the deviation from the CSF absorption model seen in some patients.

  • 23.
    Andersson, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Grip, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik.
    Lindvall, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Brändström, Helge
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Air transport of patients with intracranial air: computer model of pressure effects2003Inngår i: Aviation, Space and Environmental Medicine, ISSN 0095-6562, Vol. 74, nr 2, 138-144 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 24.
    Andersson, Oskar
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    White matter lesions in Parkinson's disease: aspects on comorbidity and motor subtypes.2016Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 25.
    Andersén, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Dahlquist, Gisela
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Damber, Jan-Erik
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Hjemdahl, Paul
    Korsgren, Olle
    Olsson, Håkan
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Svensk medicinsk forskning behöver inte mer styrning2014Inngår i: Läkartidningen, ISSN 0023-7205, Vol. 111, nr 22-23, 980-981 s.Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 26. Andreae, Laura C
    et al.
    Peukert, Daniela
    Lumsden, Andrew
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Analysis of Lrrn1 expression and its relationship to neuromeric boundaries during chick neural development2007Inngår i: Neural Development, ISSN 1749-8104, Vol. 2, nr 22, 1-16 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The Drosophila leucine-rich repeat proteins Tartan (TRN) and Capricious (CAPS) mediate cell affinity differences during compartition of the wing imaginal disc. This study aims to identify and characterize the expression of a chick orthologue of TRN/CAPS and examine its potential function in relation to compartment boundaries in the vertebrate central nervous system.

    RESULTS: We identified a complementary DNA clone encoding Leucine-rich repeat neuronal 1 (Lrrn1), a single-pass transmembrane protein with 12 extracellular leucine-rich repeats most closely related to TRN/CAPS. Lrrn1 is dynamically expressed during chick development, being initially localized to the neural plate and tube, where it is restricted to the ventricular layer. It becomes downregulated in boundaries following their formation. In the mid-diencephalon, Lrrn1 expression prefigures the position of the anterior boundary of the zona limitans intrathalamica (ZLI). It becomes progressively downregulated from the presumptive ZLI just before the onset of expression of the signalling molecule Sonic hedgehog (Shh) within the ZLI. In the hindbrain, downregulation at rhombomere boundaries correlates with the emergence of specialized boundary cell populations, in which it is subsequently reactivated. Immunocolocalization studies confirm that Lrrn1 protein is endocytosed from the plasma membrane and is a component of the endosomal system, being concentrated within the early endosomal compartment.

    CONCLUSION: Chick Lrrn1 is expressed in ventricular layer neuroepithelial cells and is downregulated at boundary regions, where neurogenesis is known to be delayed, or inhibited. The timing of Lrrn1 downregulation correlates closely with the activation of signaling molecule expression at these boundaries. This expression is consistent with the emergence of secondary organizer properties at boundaries and its endosomal localisation suggests that Lrrn1 may regulate the subcellular localisation of specific components of signalling or cell-cell recognition pathways in neuroepithelial cells.

  • 27. Aparicio, S
    et al.
    Morrison, A
    Gould, A
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Chaudhuri, C
    Rigby, P
    Krumlauf, R
    Brenner, S
    Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes.1995Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 92, nr 5, 1684-1688 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Comparative vertebrate genome sequencing offers a powerful method for detecting conserved regulatory sequences. We propose that the compact genome of the teleost Fugu rubripes is well suited for this purpose. The evolutionary distance of teleosts from other vertebrates offers the maximum stringency for such evolutionary comparisons. To illustrate the comparative genome approach for F. rubripes, we use sequence comparisons between mouse and Fugu Hoxb-4 noncoding regions to identify conserved sequence blocks. We have used two approaches to test the function of these conserved blocks. In the first, homologous sequences were deleted from a mouse enhancer, resulting in a tissue-specific loss of activity when assayed in transgenic mice. In the second approach, Fugu DNA sequences showing homology to mouse sequences were tested for enhancer activity in transgenic mice. This strategy identified a neural element that mediates a subset of Hoxb-4 expression that is conserved between mammals and teleosts. The comparison of noncoding vertebrate sequences with those of Fugu, coupled to a transgenic bioassay, represents a general approach suitable for many genome projects.

  • 28.
    Asklund, Thomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Kvarnbrink, Samuel
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Holmlund, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wibom, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hedman, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Synergistic killing of Glioblastoma Stem-like cells by Bortezomib and HDAC Inhibitors2012Inngår i: Anticancer Research, ISSN 0250-7005, Vol. 32, nr 7 ; Special Issue, 2407-2413 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.

  • 29.
    Asklund, Thomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sandström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Shahidi, Saeed
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Durable stabilization of three chordoma cases by bevacizumab and erlotinib2014Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, nr 7, 980-984 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 30.
    Asplund, Pär
    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.
    Bergenheim, A. Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Percutaneous Balloon Compression vs Percutaneous Retrogasserian Glycerol Rhizotomy for the Primary Treatment of Trigeminal Neuralgia2016Inngår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 78, nr 3, 421-428 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Despite >30 years of clinical use, the literature is still sparse when it comes to comparisons between percutaneous balloon compression (PBC) and percutaneous retrogasserian glycerol rhizolysis (PRGR) as treatments for trigeminal neuralgia.

    OBJECTIVE: To perform a retrospective cohort comparison between PBC and PRGR with regard to therapeutic effect, side effects, and complications.

    METHODS: Medical records and follow-up data from 124 primary PRGRs performed from 1986 to 2000 and 82 primary PBCs performed from 2000 to 2013 were reviewed. All patients had undergone clinical sensory testing and assessment of sensory thresholds. Analyses were performed to compare duration of pain relief, frequency of sensory disturbances, and side effects.

    RESULTS: Median duration of pain relief was 21 months after PRGR and 20 months after PBC. Both methods carried a high risk of hypesthesia/hypalgesia (P < .001) that was partly reversed with time. Decreased corneal sensibility was common after PRGR (P < .001) but not after PBC. Dysesthesia was more common after PRGR (23%) compared after PBC (4%; P < .001). Other side effects were noted but uncommon.

    CONCLUSION: PBC and PRGR are both effective as primary surgical treatment of trigeminal neuralgia. Both carry a risk of postoperative hypesthesia, but in this series, the side effect profile favored PBC. Furthermore, PBC is technically less challenging, whereas PRGR requires fewer resources. Between these 2 techniques, we propose PBC as the primary surgical technique for percutaneous treatment of trigeminal neuralgia on the basis of its lower incidence of dysesthesia, corneal hypesthesia, and technical failures.

    ABBREVIATIONS: MS, multiple sclerosisPBC, percutaneous balloon compressionPRGR, percutaneous retrogasserian glycerol rhizotomyTN, trigeminal neuralgiaThis is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work, provided it is properly cited. The work cannot be changed in any way or used commercially.

  • 31. Auer-Grumbach, Michaela
    et al.
    Bennett, D. L. H.
    Andersen, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Harms, M. B.
    Reilly, M. M.
    Weishaupt, J.
    Strom, T. M.
    Walther, T.
    Scherer, S. S.
    Zuchner, S.
    Martini, R.
    Senderek, J.
    Rare coding variants in the mme gene, encoding the metalloprotease neprilysin, are linked to late-onset axonal neuropathies2016Inngår i: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 21, nr 3, 235-235 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 32. Auer-Grumbach, Michaela
    et al.
    Toegel, Stefan
    Schabhuettl, Maria
    Weinmann, Daniela
    Chiari, Catharina
    Bennett, David L. H.
    Beetz, Christian
    Klein, Dennis
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Boehme, Ilka
    Fink-Puches, Regina
    Gonzalez, Michael
    Harms, Matthew B.
    Motley, William
    Reilly, Mary M.
    Renner, Wilfried
    Rudnik-Schoeneborn, Sabine
    Schlotter-Weigel, Beate
    Themistocleous, Andreas C.
    Weishaupt, Jochen H.
    Ludolph, Albert C.
    Wieland, Thomas
    Tao, Feifei
    Abreu, Lisa
    Windhager, Reinhard
    Zitzelsberger, Manuela
    Strom, Tim M.
    Walther, Thomas
    Scherer, Steven S.
    Zuchner, Stephan
    Martini, Rudolf
    Senderek, Jan
    Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies2016Inngår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 99, nr 3, 607-623 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Axonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade beta-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment.

  • 33. Axelsson, Markus
    et al.
    Malmeström, Clas
    Gunnarsson, Martin
    Zetterberg, Henrik
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lycke, Jan
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis2013Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, nr 11, Supplement: S, 543-543 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 34. Axelsson, Markus
    et al.
    Malmeström, Clas
    Gunnarsson, Martin
    Zetterberg, Henrik
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lycke, Jan
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis2014Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 1, 43-50 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. Objective: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). Methods: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. Results: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. Conclusions: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.

  • 35.
    Backlund, David
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Shunt surgery for idiopathic Normal Pressure Hydrocephalus: Analysis of early versus late shunt surgery, and its impact on final neurological outcome2016Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 36.
    Backlund, Tomas
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Frankel, Jennifer
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Israelsson, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Vrinnevi Hospital, Norrköping, Sweden.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Trunk sway in idiopathic normal pressure hydrocephalus: quantitative assessment in clinical practice2017Inngår i: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 54, 62-70 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In diagnosis and treatment of patients with idiopathic normal pressure hydrocephalus (iNPH), there is need for clinically applicable, quantitative assessment of balance and gait. Using a body worn gyroscopic system, the aim of this study was to assess postural stability of iNPH patients in standing, walking and during sensory deprivation before and after cerebrospinal fluid (CSF) drainage and surgery. A comparison was performed between healthy elderly (HE) and patients with various types of hydrocephalus (ventriculomegaly (VM)). Methods: Trunk sway was measured in 31 iNPH patients, 22 VM patients and 58 HE. Measurements were performed at baseline in all subjects, after CSF drainage in both patient groups and after shunt surgery in the iNPH group. Results: Preoperatively, the iNPH patients had significantly higher trunk sway compared to HE, specifically for the standing tasks (p < 0.001). Compared to VM, iNPH patients had significantly lower sway velocity during gait in three of four cases on firm support (p < 0.05). Sway velocity improved after CSF drainage and in forward-backward direction after surgery (p < 0.01). Compared to HE both patient groups demonstrated less reliance on visual input to maintain stable posture. Conclusions: INPH patients had reduced postural stability compared to HE, particularly during standing, and for differentiation between iNPH and VM patients sway velocity during gait is a promising parameter. A reversible reduction of visual incorporation during standing was also seen. Thus, the gyroscopic system quantitatively assessed postural deficits in iNPH, making it a potentially useful tool for aiding in future diagnoses, choices of treatment and clinical follow-up. 

  • 37.
    Behrens, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Measurements in Idiopathic Normal Pressure Hydrocephalus: Computerized neuropsychological test battery and intracranial pulse waves2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Idiopathic Normal Pressure Hydrocephalus (INPH) is a condition affecting gait, cognition and continence. Radiological examination reveals enlarged ventricles of the brain. A shunt that drains CSF from the ventricles to the abdomen often improves the symptoms. Much research on INPH has been focused on identifying tests that predict the outcome after shunt surgery. As part of this quest, there are attempts to find measurement methods of intracranial parameters that are valid, reliable, tolerable and safe for patients.

    Today's technologies for intracranial pressure (ICP) measurement are invasive, often requiring a burr-hole in the skull. Recently, a method for non-invasive ICP measurements was suggested: the Pulsatile Index (PI) calculated from transcranial Doppler data assessed from the middle cerebral artery. In this thesis the relation between PI and ICP was explored in INPH patients during controlled ICP regulation by lumbar infusion. The confidence interval for predicted ICP, based on measured PI was too large for the method to be of clinical utility.

    In the quest for better predictive tests for shunt success in INPH, recent studies have shown promising results with criteria based on cardiac related ICP wave amplitudes. The brain ventricular system, and the fluid surrounding the spinal cord are in contact. In this thesis it was shown that ICP waves could be measured via lumbar subarachnoid space, with a slight underestimation.

    One of the cardinal symptoms of hydrocephalus is cognitive impairment. Neuropsychological studies have demonstrated cognitive tests that are impaired and improve after shunt surgery in INPH patients. However, there is currently no standardized test battery and different studies use different tests. In response, in this thesis a fully automated computerized neuropsychological test battery was developed. The validity, reliability, responsiveness to improvement after shunt surgery and feasibility for testing INPH patients was demonstrated. It was also demonstrated that INPH patients were impaired in all subtests, compared to healthy elderly. 

  • 38.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Blekinge Centre of Competence, Blekinge Hospital Karlskrona, Karlskrona, Sweden.
    Eklund, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Smith, Cynthia
    Williams, Michael A
    Malm, Jan
    A computerized neuropsychological test battery designed for idiopathic normal pressure hydrocephalus2014Inngår i: Fluids and Barriers of the CNS, ISSN 2045-8118, Vol. 11, 22Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: A tool for standardized and repeated neuropsychological assessments in patients with idiopathic normal pressure hydrocephalus (INPH) is needed. The objective of this study was to develop a computerized neuropsychological test battery designed for INPH and to evaluate its reliability, validity and patient's ability to complete the tests.

    METHODS: Based on a structured review of the literature on neuropsychological testing in INPH, the eight tests most sensitive to the INPH cognitive profile were implemented in a computerized format. The Geriatric Depression Scale (GDS) was also included. Tests were presented on a touch-screen monitor, with animated instructions and speaker sound. The battery was evaluated with the following cohorts: A. Test-retest reliability, 44 healthy elderly; B. Validity against standard pen and pencil testing, 28 patients with various cognitive impairments; C. Ability to complete test battery, defined as completion of at least seven of the eight tests, 40 investigated for INPH.

    RESULTS: A. All except the figure copy test showed good test-retest reliability, r = 0.67-0.90; B. A high correlation was seen between conventional and computerized tests (r = 0.66-0.85) except for delayed recognition and figure copy task; C. Seventy-eight percent completed the computerized battery; Patients diagnosed with INPH (n = 26) performed worse on all tests, including depression score, compared to healthy controls.

    CONCLUSIONS: A new computerized neuropsychological test battery designed for patients with communicating hydrocephalus and INPH was introduced. Its reliability, validity for general cognitive impairment and completion rate for INPH was promising. After exclusion of the figure copy task, the battery is ready for clinical evaluation and as a next step we suggest validation for INPH and a comparison before and after shunt surgery.

    TRIAL REGISTRATION: ClinicalTrials.org NCT01265251.

  • 39.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Intracranial Pressure and Pulsatility Index:  2011Inngår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 69, nr 4, E1033-E1034 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 40.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Koskinen, Lars-Owe
    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.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Are intracranial pressure wave amplitudes measurable through lumbar puncture?2013Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, nr 4, 233-241 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

     Objective The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings. Methods In ten patients with normal pressure hydrocephalus, simultaneous recordings of the intracranial pressure (ICP; intraparenchymal) and lumbar pressure (LP; cerebrospinal fluid pressure) were performed. During registration, pressure was altered between resting pressure and 45mmHg using an infusion test. Data were analyzed regarding pulsations (i.e., amplitudes). Also, the pressure sensors were compared in a bench test. Results The correlation between intracranial and lumbar amplitudes was 0.98. At resting pressure, and moderately elevated ICP, intracranial pulse amplitudes exceeded that of lumbar space with about 0.9mmHg. At the highest ICP, the difference changed to 0.2mmHg. The bench test showed that the agreement of sensor readings was good at resting pressure, but reduced at higher amplitudes. Conclusions Compared to intracranial registrations, amplitudes measured through lumbar puncture were slightly attenuated. The bench test showed that differences were not attributable to dissimilarities of the sensor systems. A lumbar pressure amplitude measurement is an alternative to ICP recording, but the thresholds for what should be interpreted as elevated amplitudes need to be adjusted.

  • 41. Benatar, Michael
    et al.
    Stanislaw, Christine
    Reyes, Eliana
    Hussain, Sumaira
    Cooley, Anne
    Fernandez, Maria Catalina
    Dauphin, Danielle D.
    Michon, Sara-Claude
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wuu, Joanne
    Presymptomatic ALS genetic counseling and testing: Experience and recommendations2016Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 86, nr 24, 2295-2302 s.Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Remarkable advances in our understanding of the genetic contributions to amyotrophic lateral sclerosis (ALS) have sparked discussion and debate about whether clinical genetic testing should routinely be offered to patients with ALS. A related, but distinct, question is whether presymptomatic genetic testing should be offered to family members who may be at risk for developing ALS. Existing guidelines for presymptomatic counseling and testing are mostly based on small number of individuals, clinical judgment, and experience from other neurodegenerative disorders. Over the course of the last 8 years, we have provided testing and 317 genetic counseling sessions (including predecision, pretest, posttest, and ad hoc counseling) to 161 first-degree family members participating in the Pre-Symptomatic Familial ALS Study (Pre-fALS), as well as testing and 75 posttest counseling sessions to 63 individuals with familial ALS. Based on this experience, and the real-world challenges we have had to overcome in the process, we recommend an updated set of guidelines for providing presymptomatic genetic counseling and testing to people at high genetic risk for developing ALS. These recommendations are especially timely and relevant given the growing interest in studying presymptomatic ALS.

  • 42.
    Bergenheim, Tommy A
    et al.
    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.
    Larsson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. UCL Institute of Neurology, London, UK.
    Selective peripheral denervation for cervical dystonia: long-term follow-up2015Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, nr 12, 1307-1313 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: 61 procedures with selective peripheral denervation for cervical dystonia were retrospectively analysed concerning surgical results, pain, quality of life (QoL) and recurrences.

    METHODS: The patients were assessed with the Tsui torticollis scale, Visual Analogue Scale (VAS) for pain and Fugl-Meyer scale for QoL. Evaluations were performed preoperatively, early postoperatively, at 6 months, then at a mean of 42 (13-165) months. All patients underwent electromyogram at baseline, which was repeated in cases who presented with recurrence of symptoms after surgery.

    RESULTS: Six months of follow-up was available for 55 (90%) of the procedures and late follow-up for 34 (56%). The mean score of the Tsui scale was 10 preoperatively. It improved to 4.5 (p<0.001) at 6 months, and 5.3 (p<0.001) at late follow-up. VAS for pain improved from 6.5 preoperatively to 4.2 (p<0.001) at 6 months and 4 (p<0.01) at late follow-up. The Fugl-Meyer score for QoL improved from 43.3 to 46.6 (p<0.05) at 6 months, and to 51.1 (p<0.05) at late follow-up. Major reinnervation and/or change in the dystonic pattern occurred following 29% of the procedures, and led in 26% of patients to reoperation with either additional denervation or pallidal stimulation.

    CONCLUSIONS: Selective peripheral denervation remains a surgical option in the treatment of cervical dystonia when conservative measures fail. Although the majority of patients experience a significant relief of symptoms, there is a substantial risk of reinnervation and/or change in the pattern of the cervical dystonia.

  • 43.
    Bergenheim, Tommy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Asplund, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linderoth, Bengt
    Percutaneous retrogasserian balloon compression for trigeminal neuralgia: review of critical technical details and outcomes2013Inngår i: World Neurosurgery, ISSN 1878-8750, Vol. 79, nr 2, 359-368 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To describe percutaneous balloon compression (PBC) of the trigeminal rootlets as treatment for trigeminal neuralgia (TN), including history, operative techniques, outcomes, side effects, and some recent findings increasing the likelihood of a positive outcome.

    METHODS: PBC is indicated in patients with TN in whom microvascular decompression is considered less suitable. The procedure is simplified by the use of biplanar fluoroscopy, although it is usually carried out with C-arm fluoroscopy to facilitate the introduction of the needle and the visualization of the inflated catheter. In the right position, a clearly defined pear shape usually appears after injection of 0.5-0.7 mL of contrast material. The balloon is kept inflated for 1.5-3 minutes. It is crucial to obtain a pear shape because this probably is the most significant factor for obtaining good, long-lasting pain relief.

    RESULTS: An analysis of 100 consecutive PBC procedures showed an initial success rate of 90% and a median pain-free time without medication of 28 months. Subdividing these patients into primary TN (n = 77) and TN secondary to multiple sclerosis (a = 23), the median pain-free times were 33 months and 24 months (P = 0.2), indicating that the outcome may depend on the preoperative conditions.

    CONCLUSIONS: Complications and side effects include cardiovascular stress during the procedure, local hemorrhages in the cheek, postoperative sensory disturbance, masseter weakness, infections, and transitory diplopia after surgery. Measures to minimize side effects are proposed. With meticulous technique, PBC is a straightforward, effective, and fast procedure that compares well with other percutaneous therapies for TN.

  • 44.
    Bergh, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Zetterström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Graffmo, Karin Sixtensdotter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Jonsson, P. Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Lang, Lisa
    Stockholm, Sweden.
    Danielsson, Jens
    Stockholm, Sweden.
    Oliveberg, Mikael
    Stockholm, Sweden.
    Marklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping2015Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, nr 14, 4489-4494 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite considerable progress in uncovering the molecular details of protein aggregation in vitro, the cause and mechanism of protein-aggregation disease remain poorly understood. One reason is that the amount of pathological aggregates in neural tissue is exceedingly low, precluding examination by conventional approaches. We present here a method for determination of the structure and quantity of aggregates in small tissue samples, circumventing the above problem. The method is based on binary epitope mapping using anti-peptide antibodies. We assessed the usefulness and versatility of the method in mice modeling the neurodegenerative disease amyotrophic lateral sclerosis, which accumulate intracellular aggregates of superoxide dismutase-1. Two strains of aggregates were identified with different structural architectures, molecular properties, and growth kinetics. Both were different from superoxide dismutase-1 aggregates generated in vitro under a variety of conditions. The strains, which seem kinetically under fragmentation control, are associated with different disease progressions, complying with and adding detail to the growing evidence that seeding, infectivity, and strain dependence are unifying principles of neurodegenerative disease.

  • 45.
    Bergman, J.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Dring, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wuolikainen, Anna
    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.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Cytokine levels in interstitial brain fluid in progressive multiple sclerosis measured via intracerebral microdialysis2016Inngår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, 511-511 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 46.
    Bergman, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Treatment and monitoring of progressive multiple sclerosis using intrathecal monoclonal antibody therapy and cerebral microdialysi.2015Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 47.
    Bergman, Joakim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Dring, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Zetterberg, Henrik
    Blennow, Kaj
    Norgren, Niklas
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Anders
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Danderyd Hospital AB, Stockholm, Sweden..
    Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS2016Inngår i: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 3, nr 5, e271Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: In an ongoing, open-label, phase 1b study on the intrathecal administration of rituximab for progressive multiple sclerosis, an intraventricular catheter was inserted for drug delivery. The objective of this study was to characterize the limited white matter axonal injury evoked by catheter insertion by analyzing a panel of markers for tissue damage in CSF and serum.

    METHODS: Lumbar CSF and serum were collected before catheter insertion and at regular intervals during the follow-up period of 1 year. Levels of neurofilament light polypeptide (NF-L), glial fibrillary acidic protein, microtubule-associated protein tau, and S100 calcium binding protein B were measured in the CSF, and NF-L was also quantified in serum at each time point.

    RESULTS: One month after neurosurgical trauma, there was a distinct peak in NF-L concentration in both CSF and serum. In contrast, the biomarkers S100 calcium binding protein B, glial fibrillary acidic protein, and microtubule-associated protein tau did not show any significant changes. NF-L levels in both CSF and serum peaked at 1 month post surgery, returning to baseline after 6 to 9 months. A strong correlation was observed between the concentrations of NF-L in CSF and serum.

    CONCLUSIONS: The NF-L level, in CSF and serum, appears to be both a sensitive and specific marker for white matter axonal injury. This makes NF-L a valuable tool with which to evaluate acute white matter axonal damage in a clinical setting. Serum analysis of NF-L may become a convenient way to follow white matter axonal damage longitudinally.

  • 48.
    Bergström, Lisa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Irewall, Anna-Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Soderstrom, Lars
    Ögren, Joachim
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    One-Year Incidence, Time Trends, and Predictors of Recurrent Ischemic Stroke in Sweden From 1998 to 2010 An Observational Study2017Inngår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 48, nr 8, 2046- s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and Purpose-Recent data on the incidence, time trends, and predictors of recurrent ischemic stroke are limited for unselected patient populations. Methods-Data for ischemic stroke patients were obtained from The Swedish Stroke Register (Riksstroke) between 1998 and 2009 and merged with The Swedish National Inpatient Register. A reference group of patients was created by Statistics Sweden. The ischemic stroke patient cohort was divided into 4 time periods. Recurrent ischemic stroke within 1 year was recorded until 2010. Kaplan-Meier and Cox regression analyses were performed to study time trends and predictors of ischemic stroke recurrence. Results-Of 196 765 patients with ischemic stroke, 11.3% had a recurrent ischemic stroke within 1 year. The Kaplan-Meier estimates of the 1-year cumulative incidence of recurrent ischemic stroke decreased from 15.0% in 1998 to 2001 to 12.0% in 2007 to 2010 in the stroke patient cohort while the cumulative incidence of ischemic stroke decreased from 0.7% to 0.4% in the reference population. Age > 75 years, prior ischemic stroke or myocardial infarction, atrial fibrillation without warfarin treatment, diabetes mellitus, and treatment with beta-blockers or diuretics were associated with a higher risk while warfarin treatment for atrial fibrillation, lipid-lowering medication, and antithrombotic treatment (acetylsalicylic acid, dipyridamole) were associated with a reduced risk of recurrent ischemic stroke. Conclusions-The risk of recurrent ischemic stroke decreased from 1998 to 2010. Well-known risk factors for stroke were associated with a higher risk of ischemic stroke recurrence; whereas, secondary preventive medication was associated with a reduced risk, emphasizing the importance of secondary preventive treatment.

  • 49.
    Bergström, Lisa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Irewall, Anna-Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderström, Lars
    Ögren, Joachim
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    One-year incidence, time trends, and predictors of recurrent ischemic stroke in Sweden from 1998-2010: An observational studyManuskript (preprint) (Annet vitenskapelig)
  • 50.
    Bergström, Petra
    et al.
    Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    von Otter, Malin
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Staffan
    Institute of Mathematical Sciences, Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden.
    Nilsson, Ann-Charloth
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nilsson, Michael
    Institute of Neuroscience and Physiology, Centre for Brain Repair and Rehabilitation, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
    Andersen, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hammarsten, Ola
    Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Zetterberg, Henrik
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK.
    Association of NFE2L2 and KEAP1 haplotypes with amyotrophic lateral sclerosis2014Inngår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, Vol. 15, nr 1-2, 130-137 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron syndrome influenced by oxidative stress. The transcription factor Nrf2 and its repressor Keap1 constitute an important defence system in cellular protection against oxidative stress. Here we hypothesize that common genetic variations in the genes NFE2L2 and KEAP1, encoding Nrf2 and Keap1, may influence the risk and phenotype of ALS. Five hundred and twenty-two Swedish patients with sporadic ALS (SALS) and 564 Swedish control subjects were studied. Eight tag SNPs in NFE2L2 and three tag SNPs in KEAP1 were genotyped by allelic discrimination and three functional NFE2L2 promoter SNPs were genotyped by sequencing. One NFE2L2 haplotype (GGGAC) was associated with decreased risk of SALS (OR = 0.62 per allele, p = 0.003) and one haplotype in KEAP1 (CGG) was associated with later SALS onset (+3.4 years per allele, p = 0.015). When stratified by subgroup, one haplotype in NFE2L2, GAGCAGA including three functional promoter SNPs associated with high Nrf2 protein expression, was associated with 4.0 years later disease onset per allele in subgroup ALS (p = 0.008). In conclusion, these results suggest that variations in NFE2L2 and KEAP1, encoding two central proteins in cellular oxidative stress defence, may influence SALS pathogenesis.

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