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  • 1. Abel, Olubunmi
    et al.
    Powell, John F
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Al-Chalabi, Ammar
    Credibility analysis of putative disease-causing genes using bioinformatics2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e64899-Article in journal (Refereed)
    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.

  • 2. Abosch, Aviva
    et al.
    Timmermann, Lars
    Bartley, Sylvia
    Rietkerk, Hans Guido
    Whiting, Donald
    Connolly, Patrick J.
    Lanctin, David
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    An International Survey of Deep Brain Stimulation Procedural Steps2013In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 91, no 1, p. 1-11Article, review/survey (Refereed)
    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.

  • 3. Adams, D.
    et al.
    Coelho, T.
    Conceicao, I.
    Cruz, M. Waddington
    Schmidt, H.
    Buades, J.
    Campistol, J.
    Pouget, J.
    Berk, J.
    Ziyadeh, N.
    Partisano, A.
    Chen, J.
    Sweetser, M.
    Gollob, J.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Phase 2 open-label extension (OLE) study of patisiran with or without a TTR stabilizer for the treatment of hereditary ATTR (hATTR) amyloidosis with polyneuropathy2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, p. 31-32Article in journal (Other academic)
  • 4. Adams, D.
    et al.
    Coelho, T.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceicao, I.
    Waddington-Cruz, M.
    Schmidt, H.
    Campistol, J.
    Pouget, J.
    Buades, J.
    Falzone, R.
    Harrop, J.
    De Frutos, R.
    Butler, J.
    Cehelsky, J.
    Nochur, S.
    Vaishnaw, A.
    Gollob, J.
    Interim results from phase ii trial of aln-ttr02, a novel RNAi therapeutic for the treatment of familial amyloidotic polyneuropathy2013In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 18, no Supplement 2, p. 1-2Article in journal (Other academic)
  • 5. Adams, D.
    et al.
    Gonzalez-Duarte, A.
    O'Riordan, W. D.
    Yang, C. -C
    Ueda, M.
    Kristen, A. V.
    Tournev, I.
    Schmidt, H. H.
    Coelho, T.
    Berk, J. L.
    Lin, K. -P
    Vita, G.
    Attarian, S.
    Plante-Bordeneuve, V.
    Mezei, M. M.
    Campistol, J. M.
    Buades, J.
    Brannagan, T. H. , I I I
    Kim, B. J.
    Oh, J.
    Parman, Y.
    Sekijima, Y.
    Hawkins, P. N.
    Solomon, S. D.
    Polydefkis, M.
    Dyck, P. J.
    Gandhi, P. J.
    Goyal, S.
    Chen, J.
    Strahs, A. L.
    Nochur, S. V.
    Sweetser, M. T.
    Garg, P. P.
    Vaishnaw, A. K.
    Gollob, J. A.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis2018In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 379, no 1, p. 11-21Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.

    METHODS: In this phase 3 trial, we randomly assigned patients with hereditary transthyretin amyloidosis with polyneuropathy, in a 2:1 ratio, to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks. The primary end point was the change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7; range, 0 to 304, with higher scores indicating more impairment) at 18 months. Other assessments included the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating worse quality of life), 10-m walk test (with gait speed measured in meters per second), and modified body-mass index (modified BMI, defined as [weight in kilograms divided by square of height in meters] x albumin level in grams per liter; lower values indicated worse nutritional status).

    RESULTS: A total of 225 patients underwent randomization (148 to the patisiran group and 77 to the placebo group). The mean (+/- SD) mNIS+7 at baseline was 80.9 +/- 41.5 in the patisiran group and 74.6 +/- 37.0 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.0 +/- 1.7 versus 28.0 +/- 2.6 (difference, -34.0 points; P<0.001) at 18 months. The mean (+/- SD) baseline Norfolk QOL-DN score was 59.6 +/- 28.2 in the patisiran group and 55.5 +/- 24.3 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.7 +/- 1.8 versus 14.4 +/- 2.7 (difference, -21.1 points; P<0.001) at 18 months. Patisiran also showed an effect on gait speed and modified BMI. At 18 months, the least-squares mean change from baseline in gait speed was 0.08 +/- 0.02 m per second with patisiran versus -0.24 +/- 0.04 m per second with placebo (difference, 0.31 m per second; P<0.001), and the least-squares mean change from baseline in the modified BMI was -3.7 +/- 9.6 versus -119.4 +/- 14.5 (difference, 115.7; P<0.001). Approximately 20% of the patients who received patisiran and 10% of those who received placebo had mild or moderate infusion-related reactions; the overall incidence and types of adverse events were similar in the two groups.

    CONCLUSIONS: In this trial, patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis.

  • 6. Adams, David
    et al.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hund, Ernst
    Obici, Laura
    Tournev, Ivailo
    Campistol, Josep M.
    Slama, Michel S.
    Hazenberg, Bouke P.
    Coelho, Teresa
    First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy2016In: Current Opinion in Neurology, ISSN 1350-7540, E-ISSN 1473-6551, Vol. 29, p. S14-S26Article in journal (Refereed)
    Abstract [en]

    Purpose of review Early and accurate diagnosis of transthyretin familial amyloid polyneuropathy (TTR-FAP) represents one of the major challenges faced by physicians when caring for patients with idiopathic progressive neuropathy. There is little consensus in diagnostic and management approaches across Europe. Recent findings The low prevalence of TTR-FAP across Europe and the high variation in both genotype and phenotypic expression of the disease means that recognizing symptoms can be difficult outside of a specialized diagnostic environment. The resulting delay in diagnosis and the possibility of misdiagnosis can misguide clinical decision-making and negatively impact subsequent treatment approaches and outcomes. Summary This review summarizes the findings from two meetings of the European Network for TTR-FAP (ATTReuNET). This is an emerging group comprising representatives from 10 European countries with expertise in the diagnosis and management of TTR-FAP, including nine National Reference Centres. The current review presents management strategies and a consensus on the gold standard for diagnosis of TTR-FAP as well as a structured approach to ongoing multidisciplinary care for the patient. Greater communication, not just between members of an individual patient's treatment team, but also between regional and national centres of expertise, is the key to the effective management of TTR-FAP.

  • 7. Adams, David
    et al.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceicao, Isabel
    Waddington-Cruz, Marcia
    Schmidt, Hartmut
    Buades, Juan
    Campistol, Josep
    Pouget, Jean
    Berk, John
    Coelho, Teresa
    Phase 2 open-label extension study of patisiran, an investigational RNAi therapeutic for the treatment of familial amyloid polyneuropathy2015In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, no 11Article in journal (Other academic)
  • 8.
    Ahmadi, Mahboobah
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Human extraocular muscles in ALS2010In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 51, no 7, p. 3494-3501Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To investigate the general morphology, fiber type content, and myosin heavy chain (MyHC) composition of extraocular muscles (EOMs) from postmortem donors with amyotrophic lateral sclerosis (ALS) and to evaluate whether EOMs are affected or truly spared in this disease. METHODS. EOM and limb muscle samples obtained at autopsy from ALS donors and EOM samples from four control donors were processed for immunohistochemistry with monoclonal antibodies against distinct MyHC isoforms and analyzed by SDS-PAGE. In addition, hematoxylin and eosin staining and nicotinamide tetrazolium reductase (NADH-TR) activity were studied. RESULTS. Wide heterogeneity was observed in the appearance of the different EOMs from each single donor and between donors, irrespective of ALS type or onset. Pathologic morphologic findings in ALS EOMs included presence of atrophic and hypertrophic fibers, either clustered in groups or scattered; increased amounts of connective tissue; and areas of fatty replacement. The population of fibers stained with anti-MyHCslow tonic was smaller than that of MyHCIpositive fibers and was mostly located in the orbital layer in most of the ALS EOM samples, whereas an identical staining pattern for both fiber populations was observed in the control specimens. MyHCembryonic was notably absent from the ALS EOMs. CONCLUSIONS. The EOMs showed signs of involvement with altered fiber type composition, contractile protein content, and cellular architecture. However, when compared to the limb muscles, the EOMs were remarkably preserved. EOMs are a useful model for the study of the pathophysiology of ALS.

  • 9. Ajob, Leith
    et al.
    Brännström, Ingrid
    Ott, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Werneke, Ursula
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Fellow of the Royal College of Psychiatrists (FRCPsych).
    ABC om Wernickes encefalopati2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no ELZTArticle in journal (Refereed)
  • 10. Akram, Harith
    et al.
    Dayal, Viswas
    Mahlknecht, Philipp
    Georgiev, Dejan
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Jahanshahi, Marjan
    Ashburner, John
    Behrens, Tim
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK.
    Zrinzo, Ludvic
    Connectivity derived thalamic segmentation in deep brain stimulation for tremor2018In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 18, p. 130-142Article in journal (Refereed)
    Abstract [en]

    The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

  • 11. Akram, Harith
    et al.
    Limousin, Patricia
    Hyam, Jonathan
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. 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 Stimulation2015In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 93, no 4, p. 227-230Article in journal (Refereed)
    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

  • 12. Akram, Harith
    et al.
    Miller, Sarah
    Lagrata, Susie
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ashburner, John
    Behrens, Tim
    Matharu, Manjit
    Zrinzo, Ludvic
    Optimal deep brain stimulation site and target connectivity for chronic cluster headache2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, no 20, p. 2083-2091Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the mechanism of action of deep brain stimulation for refractory chronic cluster headache and the optimal target within the ventral tegmental area. Methods: Seven patients with refractory chronic cluster headache underwent high spatial and angular resolution diffusion MRI preoperatively. MRI-guided and MRI-verified electrode implantation was performed unilaterally in 5 patients and bilaterally in 2. Volumes of tissue activation were generated around active lead contacts with a finite-element model. Twelve months after surgery, voxel-based morphometry was used to identify voxels associated with higher reduction in headache load. Probabilistic tractography was used to identify the brain connectivity of the activation volumes in responders, defined as patients with a reduction of >= 30% in headache load. Results: There was no surgical morbidity. Average follow-up was 34 +/- 14 months. Patients showed reductions of 76 +/- 33% in headache load, 46 +/- 41% in attack severity, 58 +/- 41% in headache frequency, and 51 +/- 46% in attack duration at the last follow-up. Six patients responded to treatment. Greatest reduction in headache load was associated with activation in an area cantered at 6 mm lateral, 2 mm posterior, and 1 mm inferior to the midcommissural point of the third ventricle. Average responders' activation volume lay on the trigeminohypothalamic tract, connecting the trigeminal system and other brainstem nuclei associated with nociception and pain modulation with the hypothalamus, and the prefrontal and mesial temporal areas. Conclusions: We identify the optimal stimulation site and structural connectivity of the deep brain stimulation target for cluster headache, explicating possible mechanisms of action and disease pathophysiology.

  • 13. 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 University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. 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 disease2017In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 158, p. 332-345Article in journal (Refereed)
    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.

  • 14. Akram, Harith
    et al.
    Wu, Chengyuan
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Yousry, Tarek
    Jahanshahi, Marjan
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. 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 Disease2017In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, no 6, p. 874-883Article in journal (Refereed)
    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.

  • 15. Al Nimer, Faiez
    et al.
    Elliott, Christina
    Bergman, Joakim
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Khademi, Mohsen
    Dring, Ann M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Aeinehband, Shahin
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Christensen, Jeppe Romme
    Sellebjerg, Finn
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Linington, Christopher
    Olsson, Tomas
    Piehl, Fredrik
    Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination2016In: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 3, no 1, article id e191Article in journal (Refereed)
    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.

  • 16. Alakurtti, Kati
    et al.
    Johansson, Jarkko J.
    Joutsa, Juho
    Laine, Matti
    Backman, Lars
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Rinne, Juha O.
    Long-term test-retest reliability of striatal and extrastriatal dopamine D-2/3 receptor binding: study with [C-11]raclopride and high-resolution PET2015In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 35, no 7, p. 1199-1205Article in journal (Refereed)
    Abstract [en]

    We measured the long-term test-retest reliability of [C-11]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [C-11]raclopride assessments, with a 5-week retest interval. D-2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [C-11]raclopride binding in the striatum. A novel finding is the relatively low variability of [C-11]raclopride binding, providing suggestive evidence that extrastriatal D-2/3 binding can be studied in vivo with [C-11]raclopride PET to be verified in future studies.

  • 17. Al-Chalabi, Ammar
    et al.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Chandran, Siddharthan
    Chio, Adriano
    Corcia, Philippe
    Couratier, Philippe
    Danielsson, Olof
    de Carvalho, Mamede
    Desnuelle, Claude
    Grehl, Torsten
    Grosskreutz, Julian
    Holmøy, Trygve
    Ingre, Caroline
    Karlsborg, Merete
    Kleveland, Grethe
    Christoph Koch, Jan
    Koritnik, Blaz
    KuzmaKozakiewicz, Magdalena
    Laaksovirta, Hannu
    Ludolph, Albert
    McDermott, Christopher
    Meyer, Thomas
    Ropero, Bernardo Mitre
    Pardina, Jesus Mora
    Nygren, Ingela
    Petri, Susanne
    Povedano Panades, Mónica
    Salachas, Francois
    Shaw, Pamela
    Silani, Vincenzo
    Staaf, Gert
    Svenstrup, Kirsten
    Talbot, Kevin
    Tysnes, Ole-Bjørn
    Van Damme, Philip
    van der Kooi, Anneke
    Weber, Markus
    Weydt, Patrick
    Wolf, Joachim
    Hardiman, Orla
    van den Berg, Leonard H.
    July 2017 ENCALS statement on edaravone2017In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, no 7-8, p. 471-474Article in journal (Other academic)
  • 18. Alping, P.
    et al.
    Islam-Jakobsson, Protik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Novakova, L.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Björck, A.
    Axelsson, M.
    Malmeström, C.
    Fink, K.
    Frisell, T.
    Lycke, J.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Piehl, F.
    Superior efficacy and tolerability of rituximab as compared to fingolimod for MS patients switching from natalizumab due to positive JC virus serology2015In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, no 11, p. 555-555, article id P1079Article in journal (Other academic)
  • 19. Alping, Peter
    et al.
    Frisell, Thomas
    Novakova, Lenka
    Islam-Jakobsson, Protik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Björck, Anna
    Axelsson, Markus
    Malmeström, Clas
    Fink, Katharina
    Lycke, Jan
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Rituximab versus Fingolimod after Natalizumab in Multiple Sclerosis Patients2016In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 79, no 6, p. 950-958Article in journal (Refereed)
    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.

  • 20.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Ekerot, Carl-Fredrik
    The lateral reticular nucleus: integration of descending and ascending systems regulating voluntary forelimb movements2015In: Frontiers in Computational Neuroscience, ISSN 1662-5188, E-ISSN 1662-5188, Vol. 9, article id 102Article in journal (Refereed)
    Abstract [en]

    Cerebellar control of movements is dependent on mossy fiber input conveying information about sensory and premotor activity in the spinal cord. While much is known about spino-cerebellar systems, which provide the cerebellum with detailed sensory information, much less is known about systems conveying motor information. Individual motoneurones do not have projections to spino-cerebellar neurons. Instead, the fastest route is from last order spinal interneurons. In order to identify the networks that convey ascending premotor information from last order interneurons, we have focused on the lateral reticular nucleus (LRN), which provides the major mossy fiber input to cerebellum from spinal interneuronal systems. Three spinal ascending systems to the LRN have been investigated: the C3-C4 propriospinal neurones (PNs), the ipsilateral forelimb tract (iFT) and the bilateral ventral flexor reflex tract (bVFRT). Voluntary forelimb movements involve reaching and grasping together with necessary postural adjustments and each of these three interneuronal systems likely contribute to specific aspects of forelimb motor control. It has been demonstrated that the command for reaching can be mediated via C3-C4 PNs, while the command for grasping is conveyed via segmental interneurons in the forelimb segments. Our results reveal convergence of ascending projections from all three interneuronal systems in the LRN, producing distinct combinations of excitation and inhibition. We have also identified a separate descending control of LRN neurons exerted via a subgroup of cortico-reticular neurones. The LRN projections to the deep cerebellar nuclei exert a direct excitatory effect on descending motor pathways via the reticulospinal, vestibulospinal, and other supraspinal tracts, and might play a key role in cerebellar motor control. Our results support the hypothesis that the LRN provides the cerebellum with highly integrated information, enabling cerebellar control of complex forelimb movements.

  • 21.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Hultborn, H
    University of Copenhagen Department of Neuroscience and Pharmacology Copenhagen N. Denmark.
    Jankowska, E
    Sahlgrenska Academy, University of Gothenburg Department of Physiology Gothenburg Sweden.
    Pettersson, L-G
    Sahlgrenska Academy, University of Gothenburg Department of Physiology Gothenburg Sweden.
    Anders Lundberg (1920-2009).2010In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 200, no 3-4, p. 193-195Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    Anders Lundberg was one of the founding editorial board members for EBR when it began its life in 1976 under the editorship of John Eccles. He was also one of the most prolific contributors to the journal with a total of 49 papers, including a series of 16 on the topic of “integration in descending motor pathways controlling the forelimb in the cat”. He continued as an editor of the journal until volume 16 when he persuaded his younger colleague Hans Hultborn to take his place. Hans is one of the authors of the obituary. –John Rothwell

  • 22. Amirian, E. Susan
    et al.
    Armstrong, Georgina
    Zhou, Renke
    Wrensch, Margaret
    Olson, Sara
    Scheurer, Michael
    Il'yasova, Dora
    Lachance, Daniel
    Lau, Ching
    Claus, Elizabeth
    Barnholtz-Sloan, Jill
    Schildkraut, Joellen
    Ali-Osman, Francis
    Sadetzki, Siegal
    Johansen, Christoffer
    Houlston, Richard
    Jenkins, Robert
    Bernstein, Jonine
    Merrell, Ryan
    Davis, Faith
    Lai, Rose
    Shete, Sanjay
    Amos, Christopher
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa
    DEMOGRAPHICS AND LIFESTYLE FACTORS IN GLIOMA RISK: A REPORT FROM THE GLIOMA INTERNATIONAL CASE-CONTROL STUDY2016In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 18, p. 57-58Article in journal (Refereed)
  • 23. Amirian, E. Susan
    et al.
    Scheurer, Michael E.
    Wrensch, Margaret
    Olson, Sara H.
    Lai, Rose
    Lachance, Daniel
    Armstrong, Georgina
    Zhou, Renke
    Wiemels, Joseph
    Lau, Ching
    Claus, Elizabeth
    Barnholtz-Sloan, Jill
    Il'yasova, Dora
    Schildkraut, Joellen
    Houlston, Richard
    Shete, Sanjay
    Bernstein, Jonine
    Jenkins, Robert
    Davis, Faith
    Merrell, Ryan
    Johansen, Christoffer
    Sadetzki, Siegal
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa
    ATOPIC CONDITIONS, ANTIHISTAMINE USE, AND GLIOMA RISK: PRELIMINARY RESULTS FROM THE GLIOMA INTERNATIONAL CASE-CONTROL STUDY2013In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 15, no Supplement: 3, p. 32-32Article in journal (Other academic)
  • 24.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    ALS and FTD: two sides of the same coin?2013In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 12, no 10, p. 937-938Article in journal (Other academic)
  • 25.
    Andersen, Peter M.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Al-Chalabi, Ammar
    Clinical genetics of amyotrophic lateral sclerosis: what do we really know?2011In: Nature Reviews Neurology, ISSN 1759-4758, E-ISSN 1759-4766, Vol. 7, no 11, p. 603-615Article, review/survey (Refereed)
    Abstract [en]

    Hereditary amyotrophic lateral sclerosis (ALS) encompasses a group of genetic disorders characterized by adult-onset loss of the lower and upper motor neuron systems, often with involvement of other parts of the nervous system. Cases of hereditary ALS have been attributed to mutations in 12 different genes, the most common being SOD1, FUS and TARDBP-mutations in the other genes are rare. The identified genes explain 25-35% of cases of familial ALS, but identifying the remaining genes has proved difficult. Only a few genes seem to account for significant numbers of ALS cases, with many others causing a few cases each. Hereditary ALS can be inherited in an autosomal dominant, autosomal recessive or X-linked manner, and families with low disease penetrance are frequently observed. In such families, the genetic predisposition may remain unnoticed, so many patients carry a diagnosis of isolated or sporadic ALS. The only clinical feature that distinguishes recognized hereditary from apparently sporadic ALS is a lower mean age of onset in the former. All the clinical features reported in hereditary cases (including signs of extrapyramidal, cerebellar or cognitive involvement) have also been observed in sporadic cases. Genetic counseling and risk assessment in relatives depend on establishing the specific gene defect and the disease penetrance in the particular family.

  • 26.
    Andersen, Peter M.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Kuzma-Kozakiewicz, Magdalena
    Keller, Jürgen
    Aho-Oezhan, Helena E. A.
    Ciecwierska, Katarzyna
    Szejko, Natalia
    Vázquez, Cynthia
    Böhm, Sarah
    Badura-Lotter, Gisela
    Meyer, Thomas
    Petri, Susanne
    Linse, Katharina
    Hermann, Andreas
    Semb, Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Professionell Development.
    Stenberg, Erica
    Nackberg, Simona
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Professionell Development.
    Dorst, Johannes
    Uttner, Ingo
    Häggström, Ann-Cristin
    Ludolph, Albert C.
    Lulé, Dorothée
    Therapeutic decisions in ALS patients: cross-cultural differences and clinical implications2018In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 265, no 7, p. 1600-1606Article in journal (Refereed)
    Abstract [en]

    Objective: Quantitative analysis of decision-making on therapeutic options in different sociocultural context in amyotrophic lateral sclerosis (ALS).

    Methods: ALS patients (n = 244) were consecutively recruited in Germany (n = 83), Poland (n = 83), and Sweden (n = 78) in a prospective cross-cultural study (www.NEEDSinALS.com). They were interviewed on preferences for therapeutic techniques including invasive (IV) and non-invasive ventilation (NIV), as well as percutaneous endoscopic gastrostomy (PEG) and on hypothetical termination of these using quantitative questions. Using standardized questionnaires, religiousness, personal values, quality of life, and depressiveness were assessed.

    Results: NIV was most frequently used in Germany and PEG in Sweden. Swedish patients were most liberal on initiation and termination of PEG, NIV and IV. Polish patients were mostly undecided and were least likely to consider discontinuing supportive management. Current use was partly associated with age, gender and state of physical function; also, financial support explained some variance. Future preferences on therapeutic options from the patient’s perspective were also closely associated with cultural factors. The more oriented towards traditional and conservative values, the less likely patients were to decide for invasive therapeutic devices (IV, PEG), the least likely to have ideations to discontinue any device and the more likely to have an undecided attitude.

    Conclusions: Current use of therapeutic options is determined by medical condition in analogy to clinical guidelines. For future considerations, other factors such as cultural background are crucial, yielding hurdles to be regarded in the implementation of advanced directives in a multicultural environment.

  • 27.
    Andersson, Gustav
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Orädd, Greger
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Comparative Biology (UCCB).
    Sultan, Fahad
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Novikov, Lev N.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    In vivo Diffusion Tensor Imaging, Diffusion Kurtosis Imaging, and Tractography of a Sciatic Nerve Injury Model in Rat at 9.4T2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 12911Article in journal (Refereed)
    Abstract [en]

    Peripheral nerve injuries result in severe loss of sensory and motor functions in the afflicted limb. There is a lack of standardised models to non-invasively study degeneration, regeneration, and normalisation of neuronal microstructure in peripheral nerves. This study aimed to develop a non-invasive evaluation of peripheral nerve injuries, using diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and tractography on a rat model of sciatic nerve injury. 10 female Sprague Dawley rats were exposed to sciatic nerve neurotmesis and studied using a 9.4 T magnet, by performing DTI and DKI of the sciatic nerve before and 4 weeks after injury. The distal nerve stump showed a decrease in fractional anisotropy (FA), mean kurtosis (MK), axonal water fraction (AWF), and radial and axonal kurtosis (RK, AK) after injury. The proximal stump showed a significant decrease in axial diffusivity (AD) and increase of MK and AK as compared with the uninjured nerve. Both mean diffusivity (MD) and radial diffusivity (RD) increased in the distal stump after injury. Tractography visualised the sciatic nerve and the site of injury, as well as local variations of the diffusion parameters following injury. In summary, the described method detects changes both proximal and distal to the nerve injury.

  • 28.
    Andersson, Kennet
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Manchester, I. R.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cesarini, K. Giuliana
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Measurement of CSF dynamics with oscillating pressure infusion2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 128, no 1, p. 17-23Article in journal (Refereed)
    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.

  • 29.
    Andersson, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Department of Biomedical Engineering and Informatics, Umeå University Hospital.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Department of Biomedical Engineering and Informatics, Umeå University Hospital.
    Dependency of cerebrospinal fluid outflow resistance on intracranial pressure2008In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 109, no 5, p. 918-922Article in journal (Refereed)
    Abstract [en]

    OBJECT: The outflow resistance (Rout) of the cerebrospinal fluid (CSF) system has generally been accepted by most investigators as independent of intracranial pressure (ICP), but there are also those claiming that it is not. The general belief is that this question has been investigated numerous times in the past, but few studies have actually been specifically aimed at looking at this relationship, and no study has been able to provide scientific evidence to elucidate fully this fundamental and important issue. The objective of this study was to investigate the relationship between ICP and CSF outflow in 30 patients investigated for idiopathic normal-pressure hydrocephalus. METHODS: Lumbar infusion tests with constant pressure levels were performed, and ICP and corresponding flow were measured on 6 pressure levels for each patient. All data were standardized for comparison. RESULTS: In the range of moderate increases from baseline pressure (approximately 5-12 mm Hg, mean baseline pressure 11.7 mm Hg), the assumption of a pressure-independent Rout was confirmed (p = 0.5). However, when the pressure increment from baseline pressure was larger (approximately 15-22 mm Hg), the relationship had a nonlinear tendency (p < 0.05). CONCLUSIONS: The results of this study support the classic textbook theory of a pressure-independent Rout in the normal ICP range, where the CSF system is commonly operating. However, the theory might have to be questioned in regions where ICP exceeds baseline pressure by too much.

  • 30.
    Andersson, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Cederquist, Kristina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Aradottir, Steina
    Borg, Åke
    Armstrong, Georgina N.
    Shete, Sanjay
    Lau, Ching C.
    Bainbridge, Matthew N.
    Claus, Elizabeth B.
    Barnholtz-Sloan, Jill
    Lai, Rose
    Il'yasova, Dora
    Houlston, Richard S.
    Schildkraut, Joellen
    Bernstein, Jonine L.
    Olson, Sara H.
    Jenkins, Robert B.
    Lachance, Daniel H.
    Wrensch, Margaret
    Davis, Faith G.
    Merrell, Ryan
    Johansen, Christoffer
    Sadetzki, Siegal
    Bondy, Melissa L.
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer2014In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 16, no 10, p. 1333-1340Article in journal (Refereed)
    Abstract [en]

    Background: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer. The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results: We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.

  • 31. Androulidakis, Alexandros G
    et al.
    Kühn, Andrea A
    Chen, Chiung Chu
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Kempf, Florian
    Kupsch, Andreas
    Schneider, Gerd-Helge
    Doyle, Louise
    Dowsey-Limousin, Patricia
    Hariz, Marwan I
    Brown, Peter
    Dopaminergic therapy promotes lateralized motor activity in the subthalamic area in Parkinson's disease2007In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 130, no Pt 2, p. 457-468Article in journal (Other academic)
  • 32. Andrén, Kerstin
    et al.
    Wikkelsö, Carsten
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Agerskov, Simon
    Israelsson, Hanna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Hellström, Per
    Tullberg, Mats
    Long-term effects of complications and vascular comorbidity in idiopathic normal pressure hydrocephalus: a quality registry study2018In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 265, no 1, p. 178-186Article in journal (Refereed)
    Abstract [en]

    Background: There is little knowledge about the factors influencing the long-term outcome after surgery for idiopathic normal pressure hydrocephalus (iNPH).

    Objective: To evaluate the effects of reoperation due to complications and of vascular comorbidity (hypertension, diabetes, stroke and heart disease) on the outcome in iNPH patients, 2–6 years after shunt surgery.

    Methods: We included 979 patients from the Swedish Hydrocephalus Quality Registry (SHQR), operated on for iNPH during 2004–2011. The patients were followed yearly by mailed questionnaires, including a self-assessed modified Rankin Scale (smRS) and a subjective comparison between their present and their preoperative health condition. The replies were grouped according to the length of follow-up after surgery. Data on clinical evaluations, vascular comorbidity, and reoperations were extracted from the SHQR.

    Results: On the smRS, 40% (38–41) of the patients were improved 2–6 years after surgery and around 60% reported their general health condition to be better than preoperatively. Reoperation did not influence the outcome after 2–6 years. The presence of vascular comorbidity had no negative impact on the outcome after 2–6 years, assessed as improvement on the smRS or subjective improvement of the health condition, except after 6 years when patients with hypertension and a history of stroke showed a less favorable development on the smRS.

    Conclusion: This registry-based study shows no negative impact of complications and only minor effects of vascular comorbidity on the long-term outcome in iNPH.

  • 33. Angst, Jules
    et al.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Benazzi, Franco
    Gamma, Alex
    Hantouche, Elie
    Meyer, Thomas D
    Skeppar, Peter
    Vieta, Eduard
    Scott, Jan
    The HCL-32: towards a self-assessment tool for hypomanic symptoms in outpatients2005In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 88, no 2, p. 217-233Article in journal (Refereed)
    Abstract [en]

    Background: Bipolar disorders (BP) are frequently diagnosed and treated as pure depression initially; accurate diagnosis often being delayed by 8 to 10 years. In prospective studies, the presence of hypomanic symptoms in adolescence is strongly predictive of later bipolar disorders. As such, an instrument for self-assessment of hypomanic symptoms might increase the detection of suspected and of manifest, but under-treated, cases of bipolar disorders.

    Methods: The multi-lingual hypomania checklist (HCL-32) has been developed and is being tested internationally. This preliminary paper reports the performance of the scale in distinguishing individuals with BP (N=266) from those with major depressive disorder (MDD; N= 160). The samples were adult psychiatry patients recruited in Italy (N= 186) and Sweden (N=240).

    Results: The samples reported similar clinical profiles and the structure for the HCL-32 demonstrated two main factors identified as "active/elated" hypomania and "risk-taking/irritable" hypomania. The HCL-32 distinguished between BP and MDD with a sensitivity of 80% and a specificity of 51%.

    Limitations: Although the HCL-32 is a sensitive instrument for hypomanic symptoms, it does not distinguish between BP-1 and BP-11 disorders.

    Conclusions: Future studies should test if different combinations of items. possibly recording the consequences of hypomania, can distinguish between these BP subtypes.

  • 34. Antonsson, Johan
    et al.
    Eriksson, Ola
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Richter, Johan
    Zsigmond, Peter
    Wårdell, Karin
    Diffuse reflectance spectroscopy measurements for tissue-type discrimination during deep brain stimulation.2008In: Journal of neural engineering, ISSN 1741-2560, Vol. 5, no 2, p. 185-190Article in journal (Refereed)
    Abstract [en]

    Diffuse reflectance spectroscopy as a method for improving intracerebral guidance during functional neurosurgery has been investigated. An optical probe was developed for measurements during stereotactic and functional neurosurgery in man. The aim of the study was to investigate the spectral differences between white and grey matter and between white matter and functional targets. Diffuse reflectance spectroscopy measurements in ten patients were recorded at incremental steps towards and in three different functional targets (STN, GPi and Zi). The recorded spectra along the trajectory were sorted into white or grey matter, based on preoperative MRI images or the recorded spectral shape and intensity. The difference between tissue types was calculated as a quotient. Significant intensity differences between white and grey matter were found to be at least 14% (p < 0.05) and 20% (p < 0.0001) for MRI and spectral-sorted data respectively. The reflectance difference between white matter and the functional targets of GPi was higher than for STN and Zi. The results indicate that diffuse reflectance spectroscopy has a potential to be developed to a suitable complement to other intracerebral guidance methods.

  • 35.
    Arnell, Kai
    et al.
    Department of Paediatric Surgery, University Hospital, Uppsala.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Evaluation of Strata NSC and Codman Hakim adjustable cerebrospinal fluid shunts and their corresponding antisiphon devices: laboratory investigation2009In: Journal of Neurosurgery: Pediatrics, ISSN 1933-0707, E-ISSN 1933-0715, Vol. 3, no 3, p. 166-172Article in journal (Refereed)
    Abstract [en]

    OBJECT: The authors investigated and compared the in vitro characteristics of 2 CSF shunts, the Strata NSC and the Codman Hakim, and their corresponding antisiphon devices (ASDs).

    METHODS: Six new CSF shunts and the corresponding ASDs for each model were tested in an automated, computerized experimental setup based on pressure regulation. Opening pressure accuracy, resistance, sensitivity to abdominal pressure, antisiphon effect, and the influence of different ASD positions were determined.

    RESULTS: In general the shunts performed according to the manufacturers' specifications. However, at the lowest setting, the opening pressure of the Strata NSC was close to 0, and in the Codman Hakim shunt, it was higher than specified. The resistance in the Codman Hakim shunt (5.4 mm Hg/ml/min) was much higher than that in the Strata NSC (3.6 mm Hg/ml/min). Abdominal pressure affected opening pressure in both valves. Positioning the Strata ASD above or below the ventricular catheter tip resulted in higher and lower opening pressures, respectively, than when it was placed in line with the catheter. The positioning of the Codman Hakim ASD did not influence the opening pressure.

    CONCLUSIONS: Both CSF shunts work properly, but at the lowest setting the opening pressure of the Strata NSC was near 0 and in the Codman Hakim it was twice the manufacturer's specifications. The resistance in the Strata NSC was below the normal physiological range, and in the Codman Hakim device it was in the lower range of normal. The ASD did not change the shunt characteristics in the lying position and therefore might not do so in children. If this is the case, then a shunt system with an integrated ASD could be implanted at the first shunt insertion, thus avoiding a second operation and the possibility of infection.

  • 36.
    Asellus, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nordström, Peter
    Nordström, Anna-Lena
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. Department of Clinical Neuroscience, Karolinska Institutet, R5, Karolinska University Hospital/Solna, Stockholm, Sweden.
    CSF Apolipoprotein E in attempted suicide2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 225, p. 246-249Article in journal (Refereed)
    Abstract [en]

    Background: Cholesterol and cholesterol metabolism, involved in continued neural plasticity, has been associated to suicide and suicidal behavior. Apolipoprotein E (ApoE) plays an important role in the cholesterol metabolism. The purpose of this study was to investigate whether ApoE in cerebrospinal fluid was related to severity of suicidal behavior as measured by number of earlier suicide attempts, reversibility/interruptabilty and violent method of suicide attempt. Methods: CSF ApoE and 5-hydroxyindolacetic acid (5-HIAA) were measured in 42 medication free suicide attempters. Earlier suicide attempts and the reversibility of suicide attempt method were assessed with the Suicide Intent Scale (SIS) and the Freeman Scale. Suicide attempts were classified according to violence of method. Results: CSF ApoE levels significantly negatively correlated to the scores on Freeman Reversibility and there was a trend for lower CSF ApoE levels in suicide attempters using a violent method. Patients with at least one earlier suicide attempt (repeaters) showed a trend for higher CSF ApoE levels compared to suicide attempters debuting with suicidal behavior at inclusion in the study. The correlation between CSF ApoE and 5-HIAA was not significant. Limitations: The main limitations to this study were a relatively small sample size and lack of a healthy control group. Conclusion: Irreversible suicide attempts, representing a high risk for completed suicide, may be associated with lower level of ApoE in CSF.

  • 37. Asellus, Peter
    et al.
    Nordström, Peter
    Nordström, Anna-Lena
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, R5, Karolinska University Hospital/Solna.
    Plasma apolipoprotein E and severity of suicidal behaviour2016In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 190, p. 137-142Article in journal (Refereed)
    Abstract [en]

    There is evidence for association between low cholesterol levels and suicidal behaviour. Since apolipoprotein E (ApoE) is involved in the cholesterol metabolism in both the periphery and in the central nervous system; it may be of particular interest in the neurobiology of suicidal behaviour. Furthermore, hypothalamic-pituitary-adrenal (HPA) axis function, one of the main biological systems implicated in both suicidal behaviour and early-life adversity, affect ApoE levels. Very few studies have assessed plasma ApoE in relation to suicidal behaviour. The purpose of this study was to investigate levels of ApoE in plasma in relation to the severity of suicidal behaviour and life-time adversity in the form of exposure to interpersonal violence in suicide attempters. A total of 100 suicide attempters (67 women and 33 men) were enroled in the study. Information on earlier suicide attempts and age at onset of suicidal behaviour was gathered using the Karolinska Suicide History Interview. The Karolinska Interpersonal Violence Scale was used to assess exposure to interpersonal violence. Plasma ApoE was measured by immunonephelometry according to accredited routines. Patients with at least one earlier suicide attempt had significantly higher ApoE levels compared to suicide attempters debuting with suicidal behaviour at inclusion in the study. A higher number of earlier suicide attempts was significantly correlated with higher plasma ApoE levels. Age at onset was significantly negatively correlated with ApoE after adjusting for age. ApoE showed a significant positive correlation with exposure to interpersonal violence as a child in male suicide attempters. Our findings indicate that ApoE may be related to stress and trauma and the temporal severity of suicidal behaviour.

  • 38.
    Asplund, K.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Managing risk factors2011In: Special Issue: Abstracts of the 15th Congress of the EFNS, Budapest, Hungary, 2011, Oxford: Rapid Communications , 2011, Vol. 18, p. 621-621Conference paper (Refereed)
  • 39.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Persson, Olle
    Umeå University, Faculty of Social Sciences, Department of Sociology.
    Country comparisons of human stroke research since 2001: a bibliometric study2012In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 43, no 3, p. 830-837Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: This is the first bibliometric comparison between countries of the development of stroke research over time.

    METHODS: Clinical and epidemiological articles on stroke published 2001 to mid-2011 were identified in Science Citation Index Expanded. Article fractions, citation fractions, h-index, and international collaboration were calculated using the BibExcel software and adjusted for population size and gross domestic product.

    RESULTS: The United States dominated with 28.7% of the sum of article fractions and 36.2% of the sum of citation fractions. The United States, Japan, the United Kingdom, and Germany together accounted for 52.1% of articles and 61.0% of citations. When adjusted for population size or gross domestic product, several small European countries, together with Israel and Taiwan, ranked the highest. Per population, there was a negative association (r=0.60) between burden of stroke (disability-adjusted life-years lost) and number of articles per population. In China, South Korea, and Singapore, the annual growth of stroke articles was more than twice the worldwide average. Whereas multinational collaboration was common within Europe and North America, it was relatively uncommon between Asian countries.

    CONCLUSIONS: The Big 4 in scientific literature on stroke, as to both number of articles and citations, are the United States, Japan, the United Kingdom, and Germany. Many small European countries have, in relation to their size, a high scientific production. Several countries with rapidly expanding economies have very fast growth of scientific production on stroke. Our results emphasize the need for stroke research in countries with a high population burden of stroke and they highlight the role of multinational collaboration.

  • 40.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Glader, Eva-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Norrving, Bo
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Effects of Extending the Time Window of Thrombolysis to 4.5 Hours: Observations in the Swedish Stroke Register (Riks-Stroke)2011In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 42, no 9, p. 2492-2497Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: The European Cooperative Acute Stroke Study (ECASS) III trial and Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register (SITS-ISTR) data were published in 2008. Riks-Stroke, the Swedish Stroke Register, was used to explore how thrombolysis in the 3- to 4.5-hour window has been spread in different hospitals and patient groups and what effects this has had on treatment within 3 hours.

    Methods: All 76 hospitals in Sweden admitting patients with acute stroke participate in Riks-Stroke. During the study period, January 2003 to June 2010, 92 150 18- to 80-year-old patients were hospitalized for acute ischemic stroke.

    Results: After the publication of the ECASS III results in the third quarter of 2008, thrombolysis in the 3- to 4.5-hour window increased from 0.5% before publication to 2.1% in 2010. Thrombolysis in the 3- to 4.5-hour window spread somewhat faster in men than women (P=0.04) but at a similar rate in different age groups. The use of thrombolysis within 3 hours after onset of symptoms increased successively from 0.9% in 2003 to 6.6% in late 2008 and then it stabilized at 6%. The median time from arrival to the hospital to start of treatment remained unchanged at 66 to 69 minutes before and after 2008 (P=0.06).

    Conclusions: Since the end of 2008, there has been a rapid nationwide dissemination of thrombolysis in the 3- to 4.5-hour window, whereas rates in the <3-hour window have leveled off. The extended time window has not affected door-to-needle time.

  • 41.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lundström, Staffan
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    End of life after stroke: a nationwide study of 42,502 deaths occurring within a year after stroke2018In: European Stroke Journal, ISSN 2396-9873, E-ISSN 2396-9881, Vol. 3, no 1, p. 74-81Article in journal (Refereed)
    Abstract [en]

    Introduction: In the scientific literature, there is very limited empirical information on end-of-life issues after stroke in the scientific literature. The present nationwide study describes the circumstances surrounding deaths that occur within a year after a stroke. Patients and methods: Datasets from three nationwide Swedish registers (on stroke, palliative care and cause of death) were linked. Basic information was available for 42,502 unselected cases of death that occurred within a year after a stroke and more detailed information was available for 16,408 deaths. Odds ratios for characteristics of end-of-life care were calculated by logistic regression. Results: In the late phase after stroke (three months to one year), 46% of patients died in a nursing home, whereas 37% of patients died in a hospital after readmission and 10% of patients died at home. Eleven per cent of deaths were reported as being unexpected. A next of kin was present at 49% of deaths. The frequency of unattended deaths (neither next of kin nor staff were present at the time of death) ranged from 5% at home with specialised home care to 25% in hospitals. Discussion: This is, by far, the largest study published on end-of-life issues after stroke. Major differences between countries in healthcare, community services, family structure and culture may limit direct transfer of the present results to other settings. Conclusion: There is considerable discordance between presumed good death' late after stroke (dying at home surrounded by family members) and the actual circumstances at the end of life.

  • 42.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Norrving, B.
    Department of Neurology, Skane University Hospital, Lund.
    Glader, Eva-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Implementation in routine clinical practice of thrombolysis in extended time window 3-4.5 h: A nationwide swedish study2011In: Special Issue: Abstracts of the 15th Congress of the EFNS, Budapest, Hungary, 2011, Oxford: Rapid Communications , 2011, Vol. 18, p. 52-52Conference paper (Refereed)
  • 43.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sukhova, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Diagnostic procedures, treatments, and outcomes in stroke patients admitted to different types of hospitals2015In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, no 3, p. 806-812Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: In many countries, including Sweden, initiatives have been taken to reduce between-hospital differences in the quality of stroke services. We have explored to what extent hospital type (university, specialized nonuniversity, or community hospital) influences hospital performance. Methods: Riksstroke collects clinical data during hospital stay (national coverage 94%). Follow-up data at 3 months were collected using administrative registers and a questionnaire completed by surviving patients (response rate 88%). Structural data were collected from a questionnaire completed by hospital staff (response rate 100%). Multivariate analyses with adjustment for clustering were used to test differences between types of hospitals. Results: The proportion of patients admitted directly to a stroke unit was highest in community hospitals and lowest in university hospitals. Magnetic resonance, carotid imaging, and thrombectomy were more frequently performed in university hospitals, and the door-to-needle time for thrombolysis was shorter. Secondary prevention with antihypertensive drugs was used less often, and outpatient follow-up was less frequent in university hospitals. Fewer patients in community hospitals were dissatisfied with their rehabilitation. After adjusting for possible confounders, poor outcome (dead or activities of daily living dependency 3 months after stroke) was not significantly different between the 3 types of hospital. Conclusions: In a setting with national stroke guidelines, stroke units in all hospitals, and measurement of hospital performance and benchmarking, outcome (after case-mix adjustment) is similar in university, specialized nonuniversity, and community hospitals. There seems to be fewer barriers to organizing well-functioning stroke services in community hospitals compared with university hospitals.

  • 44.
    Augustian, Midhumol
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    ur Réhman, Shafiq
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Sandvig, Axel
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Norwegian University of Science and Technology (NTNU), Norway.
    Kotikawatte, Thivra
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Yongcui, Mi
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Evensmoen, Hallvard Røe
    Norwegian University of Science and Technology (NTNU), Norway.
    EEG Analysis from Motor Imagery to Control a Forestry Crane2018In: Intelligent Human Systems Integration (IHSI 2018) / [ed] Karwowski, Waldemar, Ahram, Tareq, 2018, Vol. 722, p. 281-286Conference paper (Refereed)
    Abstract [en]

    Brain-computer interface (BCI) systems can provide people with ability to communicate and control real world systems using neural activities. Therefore, it makes sense to develop an assistive framework for command and control of a future robotic system which can assist the human robot collaboration. In this paper, we have employed electroencephalographic (EEG) signals recorded by electrodes placed over the scalp. The human-hand movement based motor imagery mentalization is used to collect brain signals over the motor cortex area. The collected µ-wave (8–13 Hz) EEG signals were analyzed with event-related desynchronization/synchronization (ERD/ERS) quantification to extract a threshold between hand grip and release movement and this information can be used to control forestry crane grasping and release functionality. The experiment was performed with four healthy persons to demonstrate the proof-of concept BCI system. From this study, it is demonstrated that the proposed method has potential to assist the manual operation of crane operators performing advanced task with heavy cognitive work load.

  • 45. Axelsson, Markus
    et al.
    Malmeström, Clas
    Gunnarsson, Martin
    Zetterberg, Henrik
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lycke, Jan
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis2013In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 11, Supplement: S, p. 543-543Article in journal (Other academic)
  • 46. Axelsson, Markus
    et al.
    Malmeström, Clas
    Gunnarsson, Martin
    Zetterberg, Henrik
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lycke, Jan
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis2014In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no 1, p. 43-50Article in journal (Refereed)
    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.

  • 47. Aziz, Tipu Z.
    et al.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. UCL Institute of Neurology, Unit of Functional Neurosurgery, London, England.
    To sleep or not to sleep during deep brain stimulation surgery for Parkinson disease?2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, no 19, p. 1938-1939Article in journal (Other academic)
  • 48.
    Backman, Lars
    et al.
    Aging Research Center, Karolinska Institute and University of Stockholm, Stockholm,.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Dopamine and training-related working-memory improvement2013In: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 37, no 9, p. 2209-2219Article, review/survey (Refereed)
    Abstract [en]

    Converging evidence indicates that the neurotransmitter dopamine (DA) is implicated in working-memory (WM) functioning and that WM is trainable. We review recent work suggesting that DA is critically involved in the ability to benefit from WM interventions. Functional MRI studies reveal increased striatal BOLD activity following certain forms of WM interventions, such as updating training. Increased striatal BOLD activity has also been linked to transfer of learning to non-trained WM tasks, suggesting a neural signature of transfer. The striatal BOLD signal is partly determined by DA activity. Consistent with this assertion, PET research demonstrates increased striatal DA release during updating of information in WM after training. Genetic studies indicate larger increases in WM performance post training for those who carry advantageous alleles of DA-relevant genes. These patterns of results corroborate the role of DA in WM improvement. Future research avenues include: (a) neuromodulatory correlates of transfer; (b) the potential of WM training to enhance DA release in older adults; (c) comparisons among different WM processes (i.e., updating, switching, inhibition) regarding regional patterns of training-related DA release; and (d) gene-gene interactions in relation to training-related WM gains.

  • 49. Ballesteros, Soledad
    et al.
    Prieto, Antonio
    Mayas, Julia
    Pilar, Toril
    Ponce De León Romero, Laura
    Reales, José Manuel
    Waterworth, John
    Umeå University, Faculty of Social Sciences, Department of Informatics.
    Corrigendum: brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial2015In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 7, article id 82Article in journal (Refereed)
  • 50. Bas-Hoogendam, Janna Marie
    et al.
    van Steenbergen, Henk
    Pannekoek, J. Nienke
    Fouche, Jean-Paul
    Lochner, Christine
    Hattingh, Coenraad J.
    Cremers, Henk R.
    Furmark, Tomas
    Månsson, Kristoffer N. T.
    Frick, Andreas
    Engman, Jonas
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Carlbring, Per
    Andersson, Gerhard
    Fredrikson, Mats
    Straube, Thomas
    Peterburs, Jutta
    Klumpp, Heide
    Phan, K. Luan
    Roelofs, Karin
    Stein, Dan J.
    van der Wee, Nic. J. A.
    Sample Size Matters: A Voxel-Based Morphometry Multi-Center Mega-Analysis of Gray Matter Volume in Social Anxiety Disorder2017In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, p. S7-S7Article in journal (Refereed)
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