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  • 201.
    Edvardsson, David
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Research needed for person-centred care2011Ingår i: Versorgungsforschung für demenziell erkrankte Menschen: Health Services Research for People with Dementia / [ed] Olivia Dibelius & Wolfgang Maier, Stuttgart: W. Kohlhammer GmbH, 2011, s. 62-65Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 202.
    Edvardsson, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Winblad, Bengt
    Sandman, Per-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Good dementia care: goals, strategies and perspectives2011Ingår i: Versorgungsforschung für demenziell erkrankte Menschen: Health Services Research for People with Dementia / [ed] Olivia Dibelius & Wolfgang Maier, Stuttgart: W. Kohlhammer GmbH, 2011, s. 56-61Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 203.
    Edvardsson, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Australian Centre for Evidence-Based Aged Care (ACEBAC), La Trobe University, Australia.
    Winblad, Bengt
    Sandman, Per-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Person-centred care of people with severe Alzheimer's disease: current status and ways forward2008Ingår i: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 7, nr 4, s. 362-367Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    When caring for people with severe Alzheimer's disease (AD), the concept of the person being central is increasingly advocated in clinical practice and academia as an approach to deliver high-quality care. The aim of person-centred care, which emanates from phenomological perspectives on AD, is to acknowledge the personhood of people with AD in all aspects of their care. It generally includes the recognition that the personality of the person with AD is increasingly concealed rather than lost; personalisation of the person's care and their environment; offering shared decision-making; interpretation of behaviour from the viewpoint of the person; and prioritising the relationship as much as the care tasks. However, questions remain about how to provide, measure, and explore clinical outcomes of person-centred care. In this Review, we summarise the current knowledge about person-centred care for people with severe AD and highlight the areas in need of further research.

  • 204.
    Ehrenberg, Dieter
    et al.
    Technical University of Leipzig, Leipzig, Germany.
    Eklund, Patrik
    Department of Computer Science, Åbo Akademi, Åbo, Finland.
    Fedrizzi, Mario
    University of Trento, Trento, Italy.
    Ventre, Aldo
    University of Naples, Naples, Italy.
    Enhancing consensus in distributed environments1990Ingår i: Parallel Architectures and Neural Networks: Third Italian Workshop : Vietri Sul Mare, Salerno, Italy, 15-18 May, 1990 / [ed] E. R. Caianiello, Singapore: World Scientific, 1990, s. 403-406Konferensbidrag (Refereegranskat)
  • 205.
    Ehrsson, H Henrik
    et al.
    Karolinska Institutet.
    Fagergren, Anders
    Karolinska Institutet.
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Forssberg, Hans
    Karolinska Institutet.
    Evidence for the involvement of the posterior parietal cortex in coordination of fingertip forces for grasp stability in manipulation2003Ingår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 90, nr 5, s. 2978-2986Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Grasp stability during object manipulation is achieved by the grip forces applied normal to the grasped surfaces increasing and decreasing in phase with increases and decreases of destabilizing load forces applied tangential to the grasped surfaces. This force coordination requires that the CNS anticipates the grip forces that match the requirements imposed by the self-generated load forces. Here, we use functional MRI (fMRI) to study neural correlates of the grip-load force coordination in a grip-load force task in which six healthy humans attempted to lift an immovable test object held between the tips of the right index finger and thumb. The recorded brain activity was compared with the brain activity obtained in two control tasks in which the same pair of digits generated forces with similar time courses and magnitudes; i.e., a grip force task where the subjects only pinched the object and did not apply load forces, and a load force task, in which the subjects applied vertical forces to the object without generating grip forces. Thus neither the load force task nor the grip force task involved coordinated grip-load forces, but together they involved the same grip force and load force output. We found that the grip-load force task was specifically associated with activation of a section of the right intraparietal cortex, which is the first evidence for involvement of the posterior parietal cortex in the sensorimotor control of coordinated grip and load forces in manipulation. We suggest that this area might represents a node in the network of cortical and subcortical regions that implement anticipatory control of fingertip forces for grasp stability.

  • 206. Eisen, Andrew
    et al.
    Mezei, Michelle M
    Stewart, Heather G
    Fabros, Marife
    Gibson, Gillan
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    SOD1 gene mutations in ALS patients from British Columbia, Canada: clinical features, neurophysiology and ethical issues in management2008Ingår i: Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders, ISSN 1466-0822, E-ISSN 1743-4483, Vol. 9, nr 2, s. 108-119Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Two hundred and fifty-four ALS patients from British Columbia, Canada were screened for mutations in the gene encoding the enzyme superoxide dismutase type 1 (SOD1). Thirteen patients (5.1%) carried one of six missense mutations (A4V, G72C, D76Y, D90A, C111Y, I113T). Mutations were found both in sporadic and familial ALS cases. Atypical clinical features delayed diagnosis in some cases. The demographic and clinical features of the mutation carrying index cases are summarized, and compared with those of screened patients without mutations. The phenotypic variability between SOD1 mutation carrying patients in this study is dramatic, even among patients with the same mutation This underlines the hypothesis that ALS is a biologically heterogeneous disorder in which genetics, environment and ageing all interrelate to form the final clinical phenotype.

  • 207. Ekblad, Laura L.
    et al.
    Johansson, Jarkko
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Turku PET Centre, University of Turku, Finland.
    Helin, Semi
    Viitanen, Matti
    Laine, Hanna
    Puukka, Pauli
    Jula, Antti
    Rinne, Juha O.
    Midlife insulin resistance, APOE genotype, and late-life brain amyloid accumulation2018Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, nr 13, s. e1150-e1157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To examine whether midlife insulin resistance is an independent risk factor for brain amyloid accumulation in vivo after 15 years, and whether this risk is modulated by APOE epsilon 4 genotype. Methods This observational study examined 60 elderly volunteers without dementia (mean age at baseline 55.4 and at follow-up 70.9 years, 55.5% women) from the Finnish population-based, nationwide Health2000 study with [C-11]Pittsburgh compound B-PET imaging in 2014-2016. The participants were recruited according to their homeostatic model assessment of insulin resistance (HOMA-IR) values in the year 2000, and their APOE epsilon 4 genotype. The exposure group (IR+, n = 30) consisted of individuals with HOMA-IR > 2.17 at baseline (highest tertile of the Health2000 study population), and the control group (IR-, n = 30) consisted of individuals with HOMA-IR < 1.25 at baseline (lowest tertile). The groups were enriched for APOE epsilon 4 carriers, resulting in 50% (n = 15) APOE epsilon 4 carriers in both groups. Analyses were performed with multivariate logistic and linear regression. Results An amyloid-positive PET scan was found in 33.3% of the IR-group and 60.0% of the IR+ group (odds ratio 3.0, 95% confidence interval 1.1-8.9, p = 0.04). The increased risk was seen in carriers and noncarriers of APOE epsilon 4 genotype. Higher midlife, but not late-life continuous HOMA-IR was associated with a greater brain amyloid burden at follow-up after multivariate adjustments for other cognitive and metabolic risk factors (ss = 0.11, 95% confidence interval 0.002-0.22, p = 0.04). Conclusions These results indicate that midlife insulin resistance is an independent risk factor for brain amyloid accumulation in elderly individuals without dementia.

  • 208.
    Ekhtiari Bidhendi, Elaheh
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    SOD1 prions transmit templated aggregation and fatal ALS-like disease2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is an adult-onset fatal neurodegenerative disease characterized by a progressive degeneration of the upper and lower motor neurons. The resulting paresis begins focally, usually in one muscle, and spreads contiguously, leading to muscle wasting, progressive paralysis and eventually death. 90% of all ALS cases are sporadic, with no genetic background (sALS), while 10% are hereditary or familial (fALS). The first identified cause of ALS was mutations in the gene encoding the enzyme superoxide dismutase 1 (SOD1), which are found in 3-6% of the ALS patients. Mutations in SOD1 confer a cytotoxic gain of function on the enzyme. Cytosolic inclusions containing aggregated SOD1 in motor neurons are a hallmark of ALS, both in patients and transgenic (Tg) mice carrying mutant human SOD1s (hSOD1). These inclusions have also been reported in sporadic and familial ALS cases without SOD1 mutations, suggesting a broader role of this protein in the ALS pathology. However, the mechanism of SOD1 misfolding and aggregation, and their contribution to the disease pathogenesis, is unclear.

    Our research group has recently identified two structurally different strains of hSOD1 aggregates (denoted A and B) in the central nervous system of Tg murine models expressing full-length hSOD1 variants.

    The aim of this thesis is to investigate if the SOD1 aggregation is a collateral byproduct in the process of the disease, or if it drives ALS pathogenesis. In addition, this work investigates the spreading characteristic of the disease in vivo.

    Human SOD1 A and B seeds were prepared from spinal cords of terminally ill hSOD1 Tg mice by ultracentrifugation through a density gradient. Minute amounts of the aggregate seeds were micro-inoculated into the lumbar spinal cord of asymptomatic recipient Tg mice, overexpressing G85R mutant hSOD1 (hSOD1G85R). Mice inoculated with A or B aggregates developed early-onset fatal ALS-like disease, becoming terminally ill around 100 days after inoculation. This is nearly 200 days earlier than hSOD1G85R Tg mice inoculated with a control preparation or non-inoculated mice. Concomitantly, exponentially growing templated hSOD1 aggregation developed in the recipient mice, spreading all along the neuraxis. The pathology provoked by the A and B strains differed in aggregation growth rates, disease progression rates, aggregate distribution along the neuraxis, rates of weight loss, end-stage amounts of aggregates, and histopathology.

    Next, we explored the existence of mutant hSOD1 aggregates with prion-like properties in the spinal cord of ALS patients.  To this end, aggregate seeds were prepared from the spinal cord of the autopsy material of an ALS patient carrying the hSOD1G127X truncation mutation, as well as from mice transgenic for the same mutation. The aggregates showed a strain A-like core structure. Inoculation of both the murine and human derived seeds into the lumbar spinal cord of hSOD1 expressing mice efficiently transmitted strain A aggregation, propagating rostrally throughout the neuraxis and causing premature fatal ALS-like disease. The inoculation of human or murine control seeds had no effect. The potency of the ALS patient-derived seed was exceedingly high, and the disease was initiated under conditions plausible to exist also in the human motor system. These results demonstrate for the first time, the presence of hSOD1 aggregates with prion-like properties in human ALS.

    We extended the exploration of hSOD1 prion mechanisms by inoculating another recipient mouse line, with wild-type-like stability and essentially normal SOD activity. Mice that are hemizygous for the hSOD1D90A transgene insertion do not develop ALS pathology and have normal murine lifespans (>700 days). Homozygous mice develop ALS-like disease around 400 days-of-age. Interestingly, inoculations of both strain A and B seeds into the lumbar spinal cord of hemizygous hSOD1D90A mice induced progressive hSOD1 aggregations and premature fatal ALS-like disease after around 250 and 350 days, respectively. In contrast, hemizygous hSOD1D90A mice inoculated with a mouse control seed died from senescence-related causes at ages beyond 700 days.

    Altogether, data in this thesis shows that the hSOD1 aggregate strains are ALS transmitting prions, suggesting that prion-like growth and spread of hSOD1 aggregation is the core pathogenic mechanism of SOD1-induced ALS.

  • 209.
    Eklund, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    The Pressure Difference between Eye and Brain Changes with Posture2016Ingår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 80, nr 2, s. 269-276Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The discovery of a posture-dependent effect on the difference between intraocular pressure (IOP) and intracranial pressure (ICP) at the level of lamina cribrosa could have important implications for understanding glaucoma and idiopathic intracranial hypertension and could help explain visual impairments in astronauts exposed to microgravity. The aim of this study was to determine the postural influence on the difference between simultaneously measured ICP and IOP.

    Methods: Eleven healthy adult volunteers (age = 46 ± 10 years) were investigated with simultaneous ICP, assessed through lumbar puncture, and IOP measurements when supine, sitting, and in 9° head-down tilt (HDT). The trans–lamina cribrosa pressure difference (TLCPD) was calculated as the difference between the IOP and ICP. To estimate the pressures at the lamina cribrosa, geometrical distances were estimated from magnetic resonance imaging and used to adjust for hydrostatic effects.

    Results: The TLCPD (in millimeters of mercury) between IOP and ICP was 12.3 ± 2.2 for supine, 19.8 ± 4.6 for sitting, and 6.6 ± 2.5 for HDT. The expected 24-hour average TLCPD on earth—assuming 8 hours supine and 16 hours upright—was estimated to be 17.3mmHg. By removing the hydrostatic effects on pressure, a corresponding 24-hour average TLCPD in microgravity environment was simulated to be 6.7mmHg.

    Interpretation: We provide a possible physiological explanation for how microgravity can cause symptoms similar to those seen in patients with elevated ICP. The observed posture dependency of TLCPD also implies that assessment of the difference between IOP and ICP in upright position may offer new understanding of the pathophysiology of idiopathic intracranial hypertension and glaucoma. 

  • 210. Ekman, U.
    et al.
    Fordell, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Eriksson, J.
    Lenfeldt, N.
    Wåhlin, A.
    Eklund, A.
    Malm, J.
    Increase of frontal neuronal activity in chronic neglect after multi-sensory scanning training in virtualManuskript (preprint) (Övrigt vetenskapligt)
  • 211.
    Ekman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Domellöf, Magdalena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Lundquist, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Longitudinal changes in task-evoked brain responses in Parkinson's disease patients with and without mild cognitive impairment2014Ingår i: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 8, artikel-id 207Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cognitive deficits are common in Parkinson's disease. Previous cross-sectional research has demonstrated a link between cognitive impairments and fronto-striatal dopaminergic dysmodulation. However, longitudinal studies that link disease progression with altered task-evoked brain activity are lacking. Therefore, our objective was to longitudinally evaluate working-memory related brain activity changes in Parkinson's disease patients with and without mild cognitive impairment (MCI). Patients were recruited within a longitudinal cohort study of incident patients with idiopathic parkinsonism. We longitudinally (at baseline examination and at 12-months follow-up) compared 28 patients with Parkinson's disease without MCI with 11 patients with Parkinson's disease and MCI. Functional MRI blood oxygen level dependent signal was measured during a verbal two-back working-memory task. Patients with MCI under-recruited bilateral medial prefrontal cortex at both time-points (main effect of group: p < 0.001, uncorrected). Critically, a significant group-by-time interaction effect (p < 0.001, uncorrected) was found in the right fusiform gyrus, indicating that working-memory related activity decreased for patients with Parkinson's disease and MCI between baseline and follow-up, while patients without MCI were stable across time-points. The functional connectivity between right fusiform gyrus and bilateral caudate nucleus was stronger for patients without MCI relative to patients with MCI. Our findings support the view that deficits in working-memory updating are related to persistent fronto-striatal under-recruitments in patients with early phase Parkinson's disease and MCI. The longitudinal evolution of MCI in Parkinson's disease translates into additional task-evoked posterior cortical changes.

  • 212.
    Ekman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Fordell, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Increase of frontal neuronal activity in chronic neglect after training in virtual reality2018Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, nr 4, s. 284-292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: A third of patients with stroke acquire spatial neglect associated with poor rehabilitation outcome. New effective rehabilitation interventions are needed. Scanning training combined with multisensory stimulation to enhance the rehabilitation effect is suggested. In accordance, we have designed a virtual-reality based scanning training that combines visual, audio and sensori-motor stimulation called RehAtt((R)). Effects were shown in behavioural tests and activity of daily living. Here, we use fMRI to evaluate the change in brain activity during Posners Cuing Task (attention task) after RehAtt((R)) intervention, in patients with chronic neglect.

    Methods: Twelve patients (mean age=72.7years, SD=6.1) with chronic neglect (persistent symptoms >6months) performed the interventions 3 times/wk during 5weeks, in total 15hours. Training effects on brain activity were evaluated using fMRI task-evoked responses during the Posners cuing task before and after the intervention.

    Results: Patients improved their performance in the Posner fMRI task. In addition, patients increased their task-evoked brain activity after the VR interventions in an extended network including pre-frontal and temporal cortex during attentional cueing, but showed no training effects during target presentations.

    Conclusions: The current pilot study demonstrates that a novel multisensory VR intervention has the potential to benefit patients with chronic neglect in respect of behaviour and brain changes. Specifically, the fMRI results show that strategic processes (top-down control during attentional cuing) were enhanced by the intervention. The findings increase knowledge of the plasticity processes underlying positive rehabilitation effects from RehAtt((R)) in chronic neglect.

  • 213.
    Elgh, Eva
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Domellöf, Magdalena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Edström, Mona
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Cognitive function in early Parkinson's disease: a population-based study2009Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 16, nr 12, s. 1278-1284Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: The study aims to describe the frequency, pattern and determinants of cognitive function in patients with newly diagnosed Parkinson's disease (PD); to compare patients with impaired cognition to patients with intact cognition; and to compare to matched healthy controls.

    METHODS: Patients were identified in a longitudinal population based study of idiopathic non-drug induced parkinsonism. Eighty-eight newly diagnosed patients with PD and no dementia were included during a four year period. The patients and 30 age- and sex-matched healthy control subjects underwent a comprehensive neuropsychological assessment.

    RESULTS: Patients performed significantly worse than healthy controls in a majority of neuropsychological tests. Test results in attention, psychomotor function, episodic memory (free recall), executive function and category fluency were significantly lower in the patient group. Comparison with normative data revealed that 30% of the patients had deficits in > or =1 cognitive domain (episodic memory, executive function and verbal function). Seventy per cent of the patients had normal performance. Unified Parkinson's Disease Rating Scale (UPDRS) III sub scores; speech, facial expression, rigidity and bradykinesia were significantly higher, and disease duration shorter amongst the cognitively impaired than amongst the cognitively intact patients. Tremor showed no difference. Education level was an independent predictor of dysfunction in patients with > or =2 cognitive domains affected.

    CONCLUSION: Cognitive dysfunction is common in untreated patients in early PD, affecting attention, psychomotor function, episodic memory, executive function and category fluency. Education level was an independent predictor of severe cognitive dysfunction.

  • 214.
    Elgh, Eva
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Hu, Xiaolei
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Dynamic Trajectory of Long-Term Cognitive Improvement Up to 10 Years in Young Community-Dwelling Stroke Survivors: A Cohort Study2019Ingår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, artikel-id 97Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and objective: The trajectories of long-term and domain-specific cognitive alterations over a decade after stroke are largely unknown. This study aims to investigate the dynamic alterations of domain-specific cognitive performance among young stroke survivors over 10 years after their first stroke.

    Methods: A prospective cohort study was carried out on 38 young stroke survivors (aged 18-65 at stroke onset) living in the community at 10 years after their first stroke. The cognitive outcomes were assessed repeatedly at 1 week, 7 months, and 10 years after their first stroke on the sub-domains: process speed (Symbol search and Coding from WAIS, TMT-A), visual attention (Bells test), visuospatial function (Block design from WAIS, RCFT), executive function (TMT-B, verbal fluency), verbal function [Letter fluency (FAS) from D-KEFS and CD], working memory (Digit Span from WAIS), immediate memory (RCFT and CD), and delayed memory (RCFT and CD). Global cognition was evaluated with Mini mental state examination at the two later time-points.

    Results: We found a delayed significant improvement of working memory with total recovery 10 years after participants' stroke. Visuospatial function recovered already at 7 months and remained stable at 10-year follow-up. Process speed demonstrated a significant decrease at 10 years compared to 7 months after stroke onset, a decrease which could be compensated by enhancements of other cognitive domains. No further deterioration was found in verbal function, immediate-, and delayed memory, and executive function during 10-year follow-up. Global cognition improved by on average two points between 7 months and 10 years. Education level and fatigue showed low to moderate positive correlations with cognitive improvements.

    Conclusions: The concordance of cognitive improvements between domain-specific and global cognitions strongly suggest that some young stroke survivors do improve their cognitive outcome over a 10-year period following their first stroke. This finding fills a gap of knowledge with respect to the dynamic trajectory of post-stroke cognition, with important implications in clinical practice.

  • 215.
    El-Salhy, M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Danielsson, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Axelsson, H
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Qian, Bi-Feng
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Neuroendocrine peptide levels in the gastrointestinal tract of mice after unilateral cervical vagotomy2000Ingår i: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 88, nr 1-3, s. 15-20Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The effects of left and right unilateral cervical vagotomy on the content of several neuroendocrine peptides were studied in different parts of the murine gastrointestinal tract, known to receive vagal innervation. The neuroendocrine peptides investigated were secretin, gastric inhibitory peptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin, substance P, VIP, neurotensin, neuropeptide Y (NPY), and galanin. The neuroendocrine peptide concentration was affected after both left and right vagotomy, and that the changes in the concentrations of the neuroendocrine peptide levels occurred in all the gastrointestinal segments investigated, namely antrum, small and large intestine. However, these changes varied, depending on which side was vagotomized and the interval after vagotomy. It is concluded that the vagus nerve had an important impact on the neuroendocrine system in the murine gut. It is suggested, furthermore that the contradictory results obtained earlier on the effect of vagotomy on the gastrointestinal peptides may depend on differences in the vagotomy methods used and on differences in observation time after vagotomy.

  • 216. Emilsson, O. I.
    et al.
    Bengtsson, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Franklin, Karl A.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Toren, K.
    Benediktsdottir, B.
    Farkhooy, A.
    Weyler, J.
    Dom, S.
    De Backer, W.
    Gislason, T.
    Janson, C.
    Onset of symptoms of obstructive sleep apnoea and asthma in persistent nocturnal gastroesophageal reflux2012Ingår i: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 21, nr S1, s. 162-162Artikel i tidskrift (Övrigt vetenskapligt)
  • 217. Engdahl, E.
    et al.
    Gustafsson, R.
    Huang, J.
    Biström, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Bomfim, I. Lima
    Stridh, P.
    Khademi, M.
    Brenner, N.
    Butt, J.
    Michel, A.
    Jons, D.
    Hortlund, M.
    Alonso-Magdalena, L.
    Hedström, A. K.
    Flamand, L.
    Ihira, M.
    Yoshikawa, T.
    Andersen, O.
    Hillert, J.
    Alfredsson, L.
    Waterboer, T.
    Sundström, P.
    Olsson, T.
    Kockum, I.
    Fogdell-Hahn, A.
    Serological response against HHV-6A is associated with increased risk for multiple sclerosis2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, s. 81-82Artikel i tidskrift (Övrigt vetenskapligt)
  • 218. Engström, Christer
    et al.
    Brändström, Sven
    Sigvardsson, Sören
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Socialmedicin.
    Cloninger, C Robert
    Nylander, Per-Olof
    Bipolar disorder. III: harm avoidance a risk factor for suicide attempts2004Ingår i: Bipolar Disorders, ISSN 1398-5647, E-ISSN 1399-5618, Vol. 6, nr 2, s. 130-138Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The aim of the study was to examine whether personality, i.e. temperament and character influence suicide attempts in bipolar patients.

    Methods: Bipolar patients were recruited from lithium dispensaries. Temperament and character inventory (TCI) was administered to 100 euthymic bipolar patients and 100 controls.

    Results: Age of onset was significantly lower in patients with suicide attempts in the total bipolar group (I and II) and bipolar I patients compared with patients without suicide attempts. Bipolar (I and II) and bipolar I patients with suicide attempts were significantly higher in harm avoidance (HA) and reward dependence compared with patients without suicide attempts. Patients (I and II) with suicide attempts had significantly more anticipatory worry, fatigability and asthenia than patients without suicide attempts. Bipolar I patients with suicide attempts had significantly more fatigability and asthenia and were more dependent than patients without suicide attempts. HA was lowest in patients with no suicide attempts and no family history of suicide, higher in patients with family history of suicide or patients with suicide attempts, and significantly highest in patients with suicide attempts and family history of suicide. Patients with suicide attempts and family history of suicide had more anticipatory worry, fatigability and asthenia. Bipolar disorder was significantly correlated to HA and suicide attempts to HA and PS. Family history of suicide and gender were significantly correlated to suicide attempts.

    Conclusions: Age of onset, HA, PS, gender and family history of suicide had a moderate to very strong effect on suicide attempts in bipolar patients.

  • 219. Engström, Christer
    et al.
    Brändström, Sven
    Sigvardsson, Sören
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Socialmedicin.
    Cloninger, Robert
    Nylander, Per-Olof
    Bipolar disorder I. Temperament and character2004Ingår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 82, nr 1, s. 131-134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The nature of the relationship between personality and bipolar affective disorders is an important but unanswered question. Methods: We have studied personality in bipolar patients by using the Temperament and Character Inventory (TCI). TCI were administered to 100 euthymic bipolar patients and 100 controls from the normal population.

    Results: Bipolar patients were significantly higher in harm avoidance (HA) and lower in reward dependence (RD), self-directedness (SD), and cooperativeness (CO) than controls. Bipolar patients are more fatigable, less sentimental, more independent, less purposeful, less resourceful, less empathic, less helpful, less pure-hearted, and have less impulse control than controls. Bipolar II patients are more impulsive, more fatigable, less resourceful, and have less impulse control than bipolar I patients.

    Limitations: Our results are limited to euthymic bipolar patients and cannot be generalized to affective disorders.

    Conclusions: Even when clinically euthymic on lithium maintenance, bipolar patients continue to have a characteristic cognitive deficit. This is in agreement with cognitive theories about cognitive deficits in depression that are regarded as important vulnerability factors in mood disorders.

  • 220.
    Eriksson Domellöf, Magdalena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lundin, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Edström, Mona
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Olfactory dysfunction and dementia in newly diagnosed patients with Parkinson's disease2017Ingår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 38, s. 41-47Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Studies report that up to 90% of patients with idiopathic Parkinson's disease (PD) have olfactory dysfunction (hyposmia). Hyposmia has also been connected to cognitive impairment and dementia in PD, but no studies of newly diagnosed patients followed longer than three years exists. The present study investigates the prevalence of olfactory dysfunction at PD diagnosis, how it evolves over time and whether hyposmia increases the risk of dementia in Parkinson's disease.

    METHODS: Olfactory function was assessed with Brief Smell Identification Test (B-SIT) in 125 newly diagnosed patients with PD. They were followed for a maximum of 10 years (median six years) with extensive investigations at baseline, 12, 36, 60 and 96 months. Patients with B-SIT<9 were considered hyposmic.

    RESULTS: Hyposmia was found in 73% of the patients at diagnosis. During the follow up period of ten years 42 (46%) patients with hyposmia at baseline developed dementia compared to seven (21%) of the normosmic patients. Cox proportional hazards model showed that hyposmia at baseline (controlled for age, gender, UPDRS III and Mild Cognitive Impairment) increased the risk of developing dementia (hazard ratio (95%CI): 3.29 (1.44-7.52), p = 0.005). Only one of 22 patients with normal cognition and normal olfaction at baseline developed dementia.

    CONCLUSIONS: Olfactory dysfunction was common at the time of PD diagnosis and increased the risk of dementia up to ten years after PD diagnosis regardless of baseline cognitive function. Normal olfaction together with normal cognition at baseline predicted a benign cognitive course up to ten years after diagnosis.

  • 221. Eriksson, G.
    et al.
    Hellman, T.
    Nilsson, A. O.
    Johansson, U.
    Ekbladh, E.
    Bernspång, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    The return to work process after stroke changes over time while participating in a newly designed person-centred rehabilitation programme2018Ingår i: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 13, s. 31-31Artikel i tidskrift (Övrigt vetenskapligt)
  • 222.
    Eriksson, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Vogel, Edward K.
    Lansner, Anders
    Bergström, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Neurocognitive Architecture of Working Memory2015Ingår i: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 88, nr 1, s. 33-46Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    A crucial role for working memory in temporary information processing and guidance of complex behavior has been recognized for many decades. There is emerging consensus that working-memory maintenance results from the interactions among long-term memory representations and basic processes, including attention, that are instantiated as reentrant loops between frontal and posterior cortical areas, as well as sub-cortical structures. The nature of such interactions can account for capacity limitations, lifespan changes, and restricted transfer after working-memory training. Recent data and models indicate that working memory may also be based on synaptic plasticity and that working memory can operate on non-consciously perceived information.

  • 223.
    Eriksson, Julius
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Cardiovascular risk factors in idiopathic normal pressure hydrocephalus. - A population-based study2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 224.
    Eriksson, Marie
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. mats.eliasson@nll.se.
    Differences in cardiovascular risk factors and socioeconomic status do not explain the increased risk of death after stroke in diabetic patients: results from the Swedish Stroke Register2013Ingår i: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 35, nr Suppl. 3, s. 305-305Artikel i tidskrift (Övrigt vetenskapligt)
  • 225. Fahlström, Andreas
    et al.
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ericson, Hans
    ABC om: Trigeminus­neuralgi2014Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 51-52Artikel i tidskrift (Refereegranskat)
  • 226. Fahlström, Andreas
    et al.
    Tobieson, Lovisa
    Redebrandt, Henrietta Nittby
    Zeberg, Hugo
    Bartek, Jiri, Jr.
    Bartley, Andreas
    Erkki, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Umeå University Hospital.
    Hessington, Amel
    Troberg, Ebba
    Mirza, Sadia
    Tsitsopoulos, Parmenion P.
    Marklund, Niklas
    Differences in neurosurgical treatment of intracerebral haemorrhage: a nation-wide observational study of 578 consecutive patients2019Ingår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 161, nr 5, s. 955-965Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Supratentorial intracerebral haemorrhage (ICH) carries an excessive mortality and morbidity. Although surgical ICH treatment can be life-saving, the indications for surgery in larger cohorts of ICH patients are controversial and not well defined. We hypothesised that surgical indications vary substantially among neurosurgical centres in Sweden.

    Objective: In this nation-wide retrospective observational study, differences in treatment strategies among all neurosurgical departments in Sweden were evaluated.

    Methods: Patient records, neuroimaging and clinical outcome focused on 30-day mortality were collected on each operated ICH patient treated at any of the six neurosurgical centres in Sweden from 1 January 2011 to 31 December 2015.

    Results: In total, 578 consecutive surgically treated ICH patients were evaluated. There was a similar incidence of surgical treatment among different neurosurgical catchment areas. Patient selection for surgery was similar among the centres in terms of patient age, pre-operative level of consciousness and co-morbidities, but differed in ICH volume, proportion of deep-seated vs. lobar ICH and pre-operative signs of herniation (p < .05). Post-operative patient management strategies, including the use of ICP-monitoring, CSF-drainage and mechanical ventilation, varied among centres (p < .05). The 30-day mortality ranged between 10 and 28%.

    Conclusions: Although indications for surgical treatment of ICH in the six Swedish neurosurgical centres were homogenous with regard to age and pre-operative level of consciousness, important differences in ICH volume, proportion of deep-seated haemorrhages and pre-operative signs of herniation were observed, and there was a substantial variability in post-operative management. The present results reflect the need for refined evidence-based guidelines for surgical management of ICH.

  • 227.
    Farahmand, Dan
    et al.
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wikkelsö, Carsten
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Tisell, Magnus
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Intracranial pressure in hydrocephalus: impact of shunt adjustments and body positions2015Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, nr 2, s. 222-228Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The association between intracranial pressure (ICP) and different shunt valve opening pressures in relation to body positions is fundamental for understanding the physiological function of the shunt.

    Objective To analyse the ICP and ICP wave amplitude (AMP) at different shunt settings and body positions in patients with hydrocephalus.

    Methods In this prospective study 15 patients with communicating hydrocephalus were implanted with a ligated adjustable ventriculoperitoneal shunt. They also received a portable intraparenchymatous ICP-monitoring device. Postoperative ICP and AMP were recorded with the patients in three different body positions (supine, sitting and walking) and with the shunt ligated and open at high, medium and low valve settings. In each patient 12 10 min segments were coded, blinded and analysed for mean ICP and mean AMP using an automated computer algorithm.

    Results Mean ICP and mean AMP were lower at all three valve settings compared with the ligated shunt state (p<0.001). Overall, when compared with the supine position, mean ICP was 11.5 +/- 1.1 (mean +/- SD) mm Hg lower when sitting and 10.5 +/- 1.1 mm Hg lower when walking (p<0.001). Mean ICP was overall 1.1 mm Hg higher (p=0.042) when walking compared with sitting. The maximal adjustability difference (highest vs lowest valve setting) was 4.4 mm Hg.

    Conclusions Changing from a supine to an upright position reduced ICP while AMP only increased at trend level. Lowering of the shunt valve opening pressure decreased ICP and AMP but the difference in mean ICP in vivo between the highest and lowest opening pressures was less than half that previously observed in vitro.

  • 228. Felbecker, Ansgar
    et al.
    Camu, William
    Valdmanis, Paul N
    Sperfeld, Anne-Dorte
    Waibel, Stefan
    Steinbach, Peter
    Rouleau, Guy A
    Ludolph, Albert C
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Four familial ALS pedigrees discordant for two SOD1 mutations: are all SOD1 mutations pathogenic?2010Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 81, nr 5, s. 572-577Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: 153 mutations in the Cu/Zn superoxide dismutase (SOD1) gene have been claimed to be associated with amyotrophic lateral sclerosis (ALS) in familial and sporadic ALS in an autosomal dominant or autosomal recessive pattern with complete or reduced penetrance. The authors now report four ALS pedigrees from Finland, France, Germany and Sweden with either the D90A or E100K SOD1 mutations in some but not all affected members. After re-collecting DNA, the non-segregation of the SOD1 mutations with disease was confirmed by three independent laboratories using different PCR primers: while some of the affected patients carry SOD1 mutations, other affected family members have two wildtype/normal SOD1 genes. In addition, some unaffected members within the same families are carriers of SOD1 gene mutations. To exclude other known genetic causes, the authors ruled out mutations within the genes coding for VAPB, ANG, TDP43, FUS and DCTN1 in affected individuals in the four pedigrees.

    CONCLUSIONS: The authors find that the D90A and E100K SOD1 gene mutations found in some patients are not the exclusive cause of ALS in these pedigrees. Whether this is also the case for the other 151 SOD1 mutations reported in ALS pedigrees is unknown. The findings have consequences for genetic testing in clinical practice when diagnosing ALS and for genetic counselling in ALS. Some SOD1 mutations may be part of an oligo- or epigentic pattern of inheritance. Such a pattern of inheritance may model other oligo- or polygenetic traits responsible for other forms of ALS.

  • 229. Fietze, I
    et al.
    Penzel, T
    Alonderis, A
    Barbe, F
    Bonsignore, M R
    Calverly, P
    De Backer, W
    Diefenbach, K
    Donic, V
    Eijsvogel, M M
    Franklin, Karl A
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Gislason, T
    Grote, L
    Hedner, J
    Jennum, P
    Lavie, L
    Lavie, P
    Levy, P
    Lombardi, C
    Mallin, W
    Marrone, O
    Montserrat, J M
    Papathanasiou, E S
    Parati, G
    Plywaczewski, R
    Pretl, M
    Riha, R L
    Rodenstein, D
    Saaresranta, T
    Schulz, R
    Sliwinski, P
    Steiropoulos, P
    Svaza, J
    Tomori, Z
    Tonnesen, P
    Varoneckas, G
    Verbraecken, J
    Vesely, J
    Vitols, A
    Zielinski, J
    McNicholas, W T
    Management of obstructive sleep apnea in Europe2011Ingår i: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 12, nr 2, s. 190-197Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: In Europe, the services provided for the investigation and management of obstructive sleep apnoea (OSA) varies from country to country. The aim of this questionnaire-based study was to investigate the current status of diagnostic pathways and therapeutic approaches applied in the treatment of OSA in Europe, qualification requirements of physicians involved in diagnosis and treatment of OSA, and reimbursement of these services. Methods: Two questionnaires were sent to 39 physicians in 22 countries in Europe. In order to standardize the responses, the questionnaire was accompanied by an example. Results: Sleep centers from 21 countries (38 physicians) participated. A broad consistency among countries with respect to the following was found: pathways included referral to sleep physicians/sleep laboratories, necessity for objective diagnosis (primarily by polysomnography), use of polygraphic methods, analysis of polysomnography (PSG), indications for positive airway pressure (PAP) therapy, application of standard continuous PAP (CPAP) therapy (100% with an CPAP/APAP ratio of 2.24:1), and the need (90.5%) and management of follow-up. Differences were apparent in reimbursement of the diagnostic procedures and follow-up, in the procedures for PAP titration from home APAP titration with portable sleep apnea monitoring (38.1%) up to hospital monitoring with PSG and APAP (85.7%), and in the qualification requirements of sleep physicians. Conclusions: Management of OSA in different European countries is similar except for reimbursement rules, qualification of sleep specialists and procedures for titration of the CPAP treatment. A European network (such as the one accomplished by the European Cooperation in Science and Technology [COST] B26 Action) could be helpful for implementing these findings into health-service research in order to standardize management in a cost effective perspective.

  • 230.
    Figueira, Joao
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Öhman, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls2016Ingår i: Molecular Biosystems, ISSN 1742-206X, E-ISSN 1742-2051, Vol. 12, nr 8, s. 2562-2571Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Saliva is a biofluid that is sensitive to metabolic changes and is straightforward to collect in a non-invasive manner, but it is seldom used for metabolite analysis when studying neurodegenerative disorders. We present a procedure for both an untargeted and targeted analysis of the saliva metabolome in which nuclear magnetic resonance (NMR) spectroscopy is used in combination with multivariate data analysis. The applicability of this approach is demonstrated on saliva samples selected from the 25 year prospective Betula study, including samples from dementia subjects with either Alzheimer's disease (AD) or vascular dementia at the time of sampling or who developed it by the next sampling/assessment occasion five years later, and age-, gender-, and education-matched control individuals without dementia. Statistically significant multivariate models were obtained that separated patients with dementia from controls and revealed seven discriminatory metabolites. Dementia patients showed significantly increased concentrations of acetic acid (fold change (fc) = 1.25, p = 2 x 10(-5)), histamine (fc = 1.26, p = 0.019), and propionate (fc = 1.35, p = 0.002), while significantly decreased levels were observed for dimethyl sulfone (fc = 0.81, p = 0.005), glycerol (fc = 0.79, p = 0.04), taurine (fc = 0.70, p = 0.007), and succinate (fc = 0.62, p = 0.008). Histamine, succinate, and taurine are known to be important in AD, and acetic acid and glycerol are involved in related pathways. Dimethyl sulfone and propionate originate from the diet and bacterial flora and might reflect poorer periodontal status in the dementia patients. For these seven metabolites, a weak but statistically significant pre-diagnostic value was observed. Taken together, we present a robust and general NMR analysis approach for studying the saliva metabolome that has potential use for screening and early detection of dementia.

  • 231.
    Fischer, Håkan
    et al.
    Karolinska Institute.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Bäckman, Lars
    Karolinska Institute.
    Age-related differences in brain regions supporting successful encoding of emotional faces.2010Ingår i: Cortex, ISSN 0010-9452, E-ISSN 1973-8102, Vol. 46, nr 4, s. 490-497Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In an event-related functional Magnetic Resonance Imaging (fMRI) study, younger and older adults were presented with negative emotional (i.e., fearful) and neutral face pictures under incidental learning conditions. They were subsequently given a test of face recognition outside the scanner. Both age groups activated amygdala bilaterally as well as the right hippocampus during successful encoding of the fearful faces. Direct age comparisons revealed greater activation in right amygdala and bilateral hippocampus in the young, whereas older adults showed greater activation in the left insular and right prefrontal cortices. None of these brain areas was activated during successful encoding of neutral faces, suggesting specificity of these brain activation patterns. The results indicate an age-related shift in the neural underpinnings of negative emotional face processing from medial-temporal to neocortical regions.

  • 232.
    Flank, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Spinal cord injuries in Sweden: studies on clinical follow-ups2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    A spinal cord injury is a serious medical condition, often caused by a physical trauma. An injury to the spinal cord affects the neurotransmission between the brain and spinal cord segments below the level of injury. The SCI causes a loss of motor function, sensory function and autonomic regulation of the body, temporary or permanent. Significantly improved acute care, primary comprehensive rehabilitation and life-long structured follow-up has led to persons with spinal cord injury (SCI) living longer than ever before. However, increased long-time survival has allowed secondary conditions to emerge, like diabetes mellitus and where cardiovascular disease (CVD) now is the most common cause of death among SCI patients. Other possible CVD-related comorbidities in this patient group have been reported to be pain and mood disturbances. There is still lack of, and need for more knowledge in the field of CVD-related screening and prevention after SCI.

    The overall aim of this thesis was to contribute to a scientific ground regarding the need for CVD-related screening and prevention after SCI.

    In Paper I and Paper II, patients with wheelchair-dependent post-traumatic SCI (paraplegia) were assessed. The results in paper I showed that 80% of the examined patients had at least one cardiovascular disease risk marker irrespective of body mass index (BMI). Dyslipidemia was common for both men and women at all BMI categories. The study also showed a high prevalence of hypertension, especially in men. Paper II showed a low frequency of self-reported physical activity, where only one out of 5 persons reported undertaking physical activity >30 min/day. The physically active had lower diastolic blood pressure but no significant difference in blood lipids.

    In paper III and IV, patients with SCI (tetraplegia and paraplegia) participated in the studies. Eighty-one percent of the patients had dyslipidemia, where also a majority of the patients with normal abdominal clinical measures had dyslipidemia. Self-reported physical activity >30min/day was reported by one third of the patients. No differences were found between physically active and not physically active patients when it came to blood glucose, serum lipid values and clinical measures (paper III). Pain was common in the patient group, however, most often on a mild to moderate level. Anxiety and depression was less common than reported in other studies (paper IV).

  • 233.
    Flank, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Ramnemark, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Levi, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Wahman, Kerstin
    Fahlström, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Professionell utveckling.
    Dyslipidemia is common after spinal cord injury - independent of clinical measures2015Ingår i: Jacobs Journal of Physical Rehabilitation Medicine, ISSN 2469-3103, Vol. 1, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To survey the incidence of clinical risk markers and its correlation with established clinical measurements for cardiovascular disease (CVD) in a heterogeneous spinal cord injured (SCI) patient population.

    Design: Descriptive, cross-sectional study.

    Subjects: 78 patients with SCI, at different injury and functional level.

    Methods: Anthropometric data, blood pressure, a blood lipid panel, blood glucose and a questionnaire were analyzed.

    Results: Eighty-one percent of all patients had dyslipidemia (DL) and a majority of the patients with abdominal measures below the recommended cut-off levels had DL. Self-reported physical activity above the cut-off level was reported by 32.1%of the patients. There were no differences in clinical measures, serum lipid values and blood glucose between physically active and not active patients. No differences were seen between men/women, tetraplegia/paraplegia and wheelchair dependent/not wheelchair dependent patients.

    Conclusion: DL is common and seems to be not treated or undertreated in the studied SCI patient group with different neurological lesion and functional levels. General anthropometric clinical measures do not seem to be valid for evaluating risk for CVD in this patient group.

  • 234.
    Flank, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Ramnemark, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Levi, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Wahman, Kerstin
    Department of Neurobiology, Care Sciences and Society, Division of Neurodegeneration, Section Neurorehabilitation, Karolinska Institutet, Sweden; Rehab Station, Stockholm/Spinalis R&D Unit, Sweden.
    Fahlström, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Professionell utveckling.
    Pain, anxiety and depression in spinal cord injured patients2017Ingår i: Jacobs Journal of Physical Rehabilitation Medicine, ISSN 2469-3103, Vol. 3, nr 1, artikel-id 028Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To assess the prevalence of pain, anxiety and depression in a sample of chronic SCI patients in Northern Sweden.

    Design: Descriptive, cross-sectional study.

    Setting: Specialist Clinic at a University Hospital.

    Participants: 78 patients with chronic spinal cord injury, at different injury and functional level.

    Outcome measures: Patients registered presented pain above, at or below injury level on a Visual Analogue Scale (VAS). Patients currently on pain medication were also registered as having pain. Depression and anxiety were assessed by the Hospital Anxiety and Depression Rating Scale (HADS).

    Results: Out of 78 patients, 58 (74%) indicated current presence of pain or were on continuous pain medication. Pain above injury level was present in 32% of the patients, with a mean VAS of 15.9±20.1, range 0-60mm. Pain at injury level were present in 24% of the patients, mean VAS 11.0±17.0, range 0-50mm and 58% had pain below injury level with a mean VAS 31.4±22.3, range 0-80mm.

    Clinically significant psychological disorders were reported in 4 patients (5%) for both anxiety and depression.

    Conclusions: Pain is very common in persons with chronic SCI, but, at least in a drug-treated population, the pain is at a mild or moderate level. Anxiety and depression were found much less common than reported in other studies. Medication effects have been considered. Even in a presumably well-medicated and well-rehabilitated population, there is still a need for further optimization of pain management, including both pharmacological and non-pharmacological methods.

    Keywords: Tetraplegia; Paraplegia; Psychological Disorders; Visual Analogue Scale; Hospital Anxiety and Depression Scale

  • 235. Fogh, Isabella
    et al.
    Lin, Kuang
    Tiloca, Cinzia
    Rooney, James
    Gellera, Cinzia
    Diekstra, Frank P.
    Ratti, Antonia
    Shatunov, Aleksey
    van Es, Michael A.
    Proitsi, Petroula
    Jones, Ashley
    Sproviero, William
    Chio, Adriano
    McLaughlin, Russell Lewis
    Soraru, Gianni
    Corrado, Lucia
    Stahl, Daniel
    Del Bo, Roberto
    Cereda, Cristina
    Castellotti, Barbara
    Glass, Jonathan D.
    Newhouse, Steven
    Dobson, Richard
    Smith, Bradley N.
    Topp, Simon
    van Rheenen, Wouter
    Meininger, Vincent
    Melki, Judith
    Morrison, Karen E.
    Shaw, Pamela J.
    Leigh, P. Nigel
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Kiel University, Institute of Clinical Molecular Biology, Kiel, Germany.
    Comi, Giacomo P.
    Ticozzi, Nicola
    Mazzini, Letizia
    D'Alfonso, Sandra
    Traynor, Bryan J.
    Van Damme, Philip
    Robberecht, Wim
    Brown, Robert H.
    Landers, John E.
    Hardiman, Orla
    Lewis, Cathryn M.
    van den Berg, Leonard H.
    Shaw, Christopher E.
    Veldink, Jan H.
    Silani, Vincenzo
    Al-Chalabi, Ammar
    Powell, John
    Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis2016Ingår i: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 73, nr 7, s. 812-820Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IMPORTANCE Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disorder with a poor prognosis and a median survival of 3 years. However, a significant proportion of patients survive more than 10 years from symptom onset. OBJECTIVE To identify gene variants influencing survival in ALS. DESIGN, SETTING, AND PARTICIPANTS This genome-wide association study (GWAS) analyzed survival in data sets from several European countries and the United States that were collected by the Italian Consortium for the Genetics of ALS and the International Consortium on Amyotrophic Lateral Sclerosis Genetics. The study population included 4256 patients with ALS (3125 [73.4%] deceased) with genotype data extended to 7 174 392 variants by imputation analysis. Samples of DNA were collected from January 1, 1993, to December 31, 2009, and analyzed from March 1, 2014, to February 28, 2015. MAIN OUTCOMES AND MEASURES Cox proportional hazards regression under an additive model with adjustment for age at onset, sex, and the first 4 principal components of ancestry, followed bymeta-analysis, were used to analyze data. Survival distributions for the most associated genetic variants were assessed by Kaplan-Meier analysis. RESULTS Among the 4256 patients included in the analysis (2589 male [60.8%] and 1667 female [39.2%]; mean [SD] age at onset, 59 [12] years), the following 2 novel loci were significantly associated with ALS survival: at 10q23 (rs139550538; P = 1.87 x 10(-9)) and in the CAMTA1 gene at 1p36 (rs2412208, P = 3.53 x 10(-8)). At locus 10q23, the adjusted hazard ratio for patients with the rs139550538 AA or AT genotype was 1.61 (95% CI, 1.38-1.89; P = 1.87 x 10(-9)), corresponding to an 8-month reduction in survival compared with TT carriers. For rs2412208 CAMTA1, the adjusted hazard ratio for patients with the GG or GT genotype was 1.17 (95% CI, 1.11-1.24; P = 3.53 x 10(-8)), corresponding to a 4-month reduction in survival compared with TT carriers. CONCLUSIONS AND RELEVANCE This GWAS robustly identified 2 loci at genome-wide levels of significance that influence survival in patients with ALS. Because ALS is a rare disease and prevention is not feasible, treatment that modifies survival is the most realistic strategy. Therefore, identification of modifier genes that might influence ALS survival could improve the understanding of the biology of the disease and suggest biological targets for pharmaceutical intervention. In addition, genetic risk scores for survival could be used as an adjunct to clinical trials to account for the genetic contribution to survival.

  • 236. Foltynie, T
    et al.
    Zrinzo, L
    Martinez-Torres, I
    Tripoliti, E
    Petersen, E
    Holl, E
    Aviles-Olmos, I
    Jahanshahi, M
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Limousin, P
    MRI-guided STN DBS in Parkinson's disease without microelectrode recording: efficacy and safety2011Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 82, nr 4, s. 358-363Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a commonly employed therapeutic procedure for patients with Parkinson's disease uncontrolled by medical therapies. This series describes the outcomes of 79 consecutive patients that underwent bilateral STN DBS at the National Hospital for Neurology and Neurosurgery between November 2002 and November 2008 using an MRI-guided surgical technique without microelectrode recording. Patients underwent immediate postoperative stereotactic MR imaging. The mean (SD) error in electrode placement was 1.3 (0.6)&emsp14;mm. There were no haemorrhagic complications. At a median follow-up period of 12&emsp14;months, there was a mean improvement in the off-medication motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) of 27.7 points (SD 13.8) equivalent to a mean improvement of 52% (p<0.0001). In addition, there were significant improvements in dyskinesia duration, disability and pain, with a mean reduction in on-medication dyskinesia severity (sum of dyskinesia duration, disability and pain from UPDRS IV) from 3.15 (SD 2.33) pre-operatively, to 1.56 (SD 1.92) post-operatively (p=0.0001). Quality of life improved by a mean of 5.5 points (median 7.9 points, SD 17.3) on the Parkinson's disease Questionnaire 39 summary index. This series confirms that image-guided STN DBS without microelectrode recording can lead to substantial improvements in motor disability of well-selected PD patients with accompanying improvements in quality of life and most importantly, with very low morbidity.

  • 237.
    Fordell, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Virtual Reality for Enriched Rehabilitation of Stroke Patients with Spatial Neglect: Diagnostics and the Rehabilitation Effect on Spatial Attention and Neuronal Activity2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: Approximately a third of all stroke patients develop spatial neglect, a debilitating symptom associated with poor outcome. Spatial neglect is clinically defined as a deficit in processing and responding to stimuli presented on the contralesional side of the body, or the space surrounding that side of the body. The heterogenetic, multi-sensory nature of the symptoms renders it difficult to diagnose and treat; therefor effective methods for screening and intervention for neglect are needed. Virtual reality (VR) is a method of brain–computer interaction that involves realtime simulation of an environment, scenario or activity that allows for user interaction and targets multiple senses. We hypothesize that VR can facilitate identification of spatial neglect in stroke patients and that training with this interface will improve patient’s functional outcome, through stimulation to neuronal networks including those controlling attention.

    Objective: The objective was to construct and validate a computerized test battery for spatial neglect and to investigate its usability in stroke patients. Also to design and develop a VR rehabilitation method for spatial neglect and to evaluate its effects on spatial attention and on neuronal activity in the brain.

    Method: We designed, developed and evaluated a new concept for assessment (VR-DiSTRO®) and training (RehAtt®) of spatial attention, using VR technology. The hardware consisted of a PC, monitor, 3D-glasses and a force feedback device to control the tasks (i.e., a robotic pen). The software enabled targets to be moved, rotated and manipulated in the 3D environment using the robotic pen. RehAtt® made it possible to combine intense visual scanning training, multi-sensory stimulation (i.e., audio, visual, tactile) and sensory-motor activation of the contralesional arm. In a first study on 31 stroke patients we performed a construct validation of VR-DiSTRO® against Rivermead Behavioural Test Battery (BIT) and investigated the usability. In a second study, 15 subjects with chronic spatial neglect (symptoms >6 month) had self-training, 3 x 1 hour for 5 weeks using RehAtt®. Outcome were measured by changes in neglect tests and in Cathrine Bergego Scale (CBS). Training-related changes in neuronal activity of the brain was studied using fMRI during task and in resting state.

    Results: VR-DiSTRO® correctly identified all patients with neglect. The sensitivity was 100% and the specificity 82% for VR-DiSTRO® compared to BIT. Usability was high and no side-effects were noted. Using repeated measurement analysis, improvements due to the RehAtt® intervention were found for Baking tray task (p < 0.001), Star cancellation test (p = 0.006) and Extinction test (p = 0.05). Improvements were also seen in the Posner task as fewer missed targets (p = 0.024). Improvement in activities of daily living (CBS) was shown immediately after training (p < 0.01) and patients still reported improvement at 6 months follow-up. Trainingrelated changes in neuronal activity were seen as an increased task-evoked brain activity in prefrontal and temporal cortex, mainly outside the attention network but in related cortical areas. During resting state, changes in network connectivity were seen after intervention with RehAtt® in the Dorsal Attention Network (DAN) and interhemispheric connectivity.

    Conclusion: VR-DiSTRO® identified visuospatial neglect in stroke patients quickly and with a high accuracy. RehAtt® training improved in spatial attention in chronic neglect with transfer to functions in daily living. Increased neuronal brain activity was found in and between attention networks and related brain structures. This could represent a compensatory effect in addition to sign of a restorative effect from the RehAtt training. The results obtained in this study are promising, encourage further development of the methods and merit for further studies.

  • 238.
    Fordell, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bodin, Kenneth
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Högpresterande beräkningscentrum norr (HPC2N).
    Bucht, Gustaf
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    A virtual reality test battery for assessment and screening of spatial neglect2011Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 123, nr 3, s. 167-174Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background – There is a need for improved screening methods for spatial neglect.

    Aim – To construct a VR-test battery and evaluate its accuracy and usability in patients with acute stroke.

    Method –  VR-DiSTRO consists of a standard desktop computer, a CRT monitor and eye shutter stereoscopic glasses, a force feedback interface, and software, developed to create an interactive and immersive 3D experience. VR-tests were developed and validated to the conventional Star Cancellation test, Line bisection, Baking Tray Task (BTT), and Visual Extinction test. A construct validation to The Rivermead Behavioral Inattention Test, used as criterion of visuospatial neglect, was made. Usability was assessed according to ISO 9241-11.

    Results –  Thirty-one patients with stroke were included, 9/31 patients had neglect. The sensitivity was 100% and the specificity 82% for the VR-DiSTRO to correctly identify neglect. VR-BTT and VR-Extinction had the highest correlation (r2 = 0.64 and 0.78), as well as high sensitivity and specificity. The kappa values describing the agreement between traditional neglect tests and the corresponding virtual reality test were between 0.47–0.85. Usability was assessed by a questionnaire; 77% reported that the VR-DiSTRO was ‘easy’ to use. Eighty-eight percent reported that they felt ‘focused’, ‘pleased’ or ‘alert’. No patient had adverse symptoms. The test session took 15 min.

    Conclusions –  The VR-DiSTRO quickly and with a high accuracy identified visuospatial neglect in patients with stroke in this construct validation. The usability among elderly patients with stroke was high. This VR-test battery has the potential to become an important screening instrument for neglect and a valuable adjunct to the neuropsychological assessment.

  • 239.
    Fordell, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bodin, Kenneth
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Högpresterande beräkningscentrum norr (HPC2N).
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    RehAtt – scanning training for neglect enhanced by multi-sensory stimulation in Virtual Reality2016Ingår i: Topics in Stroke Rehabilitation, ISSN 1074-9357, E-ISSN 1945-5119, Vol. 23, nr 3, s. 191-199Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is a lack of effective treatment for neglect. We have developed a new training method, RehAtt (TM). The objective of this study was to determine whether RehAtt (TM) improves spatial attention in chronic neglect after stroke. Methods: RehAtt (TM) consists of a computer with monitor, 3D glasses, and a force feedback interface (Robotic pen) giving sensory motor activation to the contra-lesional arm. The software combines visual scanning training with multi-sensory stimulation in 3D virtual reality (VR) game environment. Fifteen stroke patients with chronic neglect (duration > 6 month) had repeated baseline evaluations to confirm stability of symptoms. There were no test-retest effects for any of the tests. Thereafter, all patients trained 15 h in RehAtt (TM) (3 x 1 h for 5 weeks). A neglect test battery and Catherine Bergego Scale, CBS, were used to assess behavioral outcome after intervention. CBS was also used at a 6-month follow-up. Results: Using repeated measurement analysis improvements due to the training were found for Star cancellation test (p = 0.006), Baking tray task (p < 0.001), and Extinction test (p = 0.05). In the Posner task improvements were seen fewer missed targets (p = 0.024). CBS showed improvements in activities of daily life immediately after training (p < 0.01). After 6 months the patients still reported improvement in CBS. Conclusion: RehAtt (TM) is a new concept for rehabilitation of neglect. Training with the VR-method improved spatial attention and showed transfer to improved spatial attention in activities of daily living in chronic neglect. Our results are promising and merit further studies.

  • 240.
    Fordell, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Wahlin, A.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ekman, U.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Rehabilitation of chronic spatial neglect strengthens functional connectivity between nodes of the dorsal attention network2018Ingår i: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 13, s. 42-42Artikel i tidskrift (Övrigt vetenskapligt)
  • 241.
    Fordell, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ekman, U.
    Lenfeldt, N.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Rehabilitation in chronic neglect using VR strengthens connectivity between nodes of the dorsal attention network2018Ingår i: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 13, s. 50-50Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    More knowledge is required about the neural mechanisms of functional recovery of spatial neglect in chronic phase after stroke. In this functional magnetic resonance imaging (fMRI) study, we aimed to evaluate changes in resting state functional connectivity (FC) within the dorsal attention network (DAN) in chronic neglect after scanning training in VR that previously shown improvement in left side awareness in behavioral tests and activity of daily living. (Fordell et al 2016)

    Method: Thirteen subjects with chronic spatial neglect (mean duration ¼ 43 months, SD ¼ 29 months) underwent resting state fMRI at baseline and after 15 hours RehAtt training (3x1hr / week for 5 weeks). RehAtt scanning training in 3D includes multi-sensory stimulation and is controlled by their contra-lesional hand using a robotic pen (force-feedback). The analysis specifically examined resting state functional connectivity within the DAN. In addition, using spatial concordance correlation, changes in the spatial topology of the DAN to other networks were analyzed.

    Results: We found an increase in interhemispheric FC between the right FEF and the left IPS following training (pre: 0.33 0.17 [mean SD]; post: 0.45 0.13; p ¼ 0.004). The spatial concordance analyses indicated that training had stronger influence on the DAN compared to other networks.

    Conclusion: VR training that improved left side awareness in chronic stroke patients also increased connectivity within the DAN. Specifically, a region responsible for saccadic eye movement to the left became more integrated with the left posterior parietal cortex. These results highlight a mechanism that can be exploited in the rehabilitation of chronic spatial neglect

  • 242.
    Forsberg, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Graffmo, Karin Sixtensdotter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Pakkenberg, Bente
    Weber, Markus
    Nielsen, Martin
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Munch Andersen, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS/FTD-associated genes2019Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, nr 8, s. 861-869Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: A hallmark of amyotrophic lateral sclerosis (ALS) caused by mutations in superoxide dismutase-1 (SOD1) are inclusions containing SOD1 in motor neurons. Here, we searched for SOD1-positive inclusions in 29 patients carrying ALS-linked mutations in six other genes.

    Methods: A panel of antibodies that specifically recognise misfolded SOD1 species were used for immunohistochemical investigations of autopsy tissue.

    Results: The 18 patients with hexanucleotide-repeat-expansions in C9orf72 had inclusions of misfolded wild type (WT) SOD1(WT) in spinal motor neurons. Similar inclusions were occasionally observed in medulla oblongata and in the motor cortex and frontal lobe. Patients with mutations in FUS, KIF5A, NEK1, ALSIN or VAPB, carried similar SOD1(WT) inclusions. Minute amounts of misSOD1(WT) inclusions were detected in 2 of 20 patients deceased from non-neurological causes and in 4 of 10 patients with other neurodegenerative diseases. Comparison was made with 17 patients with 9 different SOD1 mutations. Morphologically, the inclusions in patients with mutations in C9orf72HRE, FUS, KIF5A, NEK1, VAPB and ALSIN resembled inclusions in patients carrying the wildtype-like SOD1(D90A) mutation, whereas patients carrying unstable SOD1 mutations (A4V, V5M, D76Y, D83G, D101G, G114A, G127X, L144F) had larger skein-like SOD1-positive inclusions.

    Conclusions and relevance Abundant inclusions containing misfolded SOD1(WT) are found in spinal and cortical motor neurons in patients carrying mutations in six ALS-causing genes other than SOD1. This suggests that misfolding of SOD1(WT) can be part of a common downstream event that may be pathogenic. The new anti-SOD1 therapeutics in development may have applications for a broader range of patients.

  • 243. Forsberg, L.
    et al.
    Johansson, S.
    Nordin, N.
    Hillert, J.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lycke, J.
    Burman, J.
    Landtblom, A. -M
    Walentin, F.
    Martin, C.
    Nilsson, P.
    Dahle, C.
    Piehl, F.
    Olsson, T.
    A Swedish nationwide pharmaco-epidemiological and genetic study (IMSE) of the long-term safety and efficacy of dimethyl fumarate2015Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, s. 286-287Artikel i tidskrift (Övrigt vetenskapligt)
  • 244. Forsberg, L.
    et al.
    Kågström, S.
    Fält, A.
    Berglund, A.
    Hillert, J.
    Nilsson, P.
    Dahle, C.
    Svenningsson, A.
    Lycke, J.
    Landtblom, A. -M
    Burman, J.
    Martin, C.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Gunnarsson, M.
    Piehl, F.
    Olsson, T.
    Clinical effectiveness of dimethyl fumarate with focus on patients treated at least 36 months - a Swedish nationwide study of the long-term effectiveness and safety of dimethyl fumarate (IMSE5)2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, s. 316-317Artikel i tidskrift (Övrigt vetenskapligt)
  • 245. Forsberg, L.
    et al.
    Kågström, S.
    Fält, A.
    Hillert, J.
    Nilsson, P.
    Dahle, C.
    Svenningsson, A.
    Lycke, J.
    Landtblom, A. -M
    Burman, J.
    Martin, C.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Gunnarsson, M.
    Piehl, F.
    Olsson, T.
    A Swedish Nationwide study of the long-term effectiveness and safety of teriflunomid based on data from the Swedish "Immunomodulation and Multiple Sclerosis Epidemiology" Study (IMSE 4)2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, s. 316-316Artikel i tidskrift (Övrigt vetenskapligt)
  • 246. Forslund, E B
    et al.
    Granström, A
    Richard, Levi
    Rehab Station Stockholm R & D Unit, Neurotec Department, Karolinska Institutet, Sweden ; Spinalis SCI Research Unit, Neurotec Department, Karolinska Institutet, Sweden.
    Westgren, N
    Hirschfeld, H
    Transfer from table to wheelchair in men and women with spinal cord injury: coordination of body movement and arm forces2007Ingår i: Spinal Cord, ISSN 1362-4393, E-ISSN 1476-5624, Vol. 45, nr 1, s. 41-48Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    STUDY DESIGN: A complex set-up was used to investigate kinematics and ground reaction forces.

    SETTING: Motor Control and Physical Therapy Research Laboratory, Neurotec Department, Karolinska Institutet, Huddinge, Sweden.

    OBJECTIVE: To investigate how men and women with spinal cord injury (SCI) perform transfers from table to wheelchair with regard to timing and magnitude of force generation beneath the hands and associated body movements.

    METHODS: A total of 13 subjects (seven men, six women) with thoracic SCI. Kinematics of body movement were recorded (Elite 2000 system) simultaneously with the signals from three force plates (AMTI) placed beneath the buttocks and hands. Temporal and spatial parameters regarding head, trunk and trailing arm displacement, loading amplitudes and loading torque directions of both hands were analyzed for each trial and subject and compared between genders.

    RESULTS: Men and women used similar amplitudes of head bending and forward displacement of the trailing shoulder, while female subjects had significantly larger trunk rotation. Both genders applied significantly more weight on the trailing hand. Differences between genders were seen in direction and timing of peak torque beneath the hands.

    CONCLUSIONS: The forces beneath the trailing hand were larger than those in the leading, if there is weakness or pain in one arm, this arm should be selected as the leading. To avoid excessive load on the arms, technical aids and environmental factors should be very well adapted.

    SPONSORSHIP: This project was funded by the Swedish Research Council and the Health Care Science Committee of Karolinska Institutet.

  • 247.
    Fowler, Christopher J.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    The potential of inhibitors of endocannabinoid metabolism as anxiolytic and antidepressive drugs-A practical view2015Ingår i: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 25, nr 6, s. 749-762Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The endocannabinoid system, comprising cannabinoid CB1 and CB2 receptors, their endogenous ligands anandamide and 2-arachidonoylglyerol, and their synthetic and metabolic enzymes, are involved in many biological processes in the body, ranging from appetite to bone turnover. Compounds inhibiting the breakdown of anandamide and 2-arachidonoylglycerol increase brain levels of these lipids and thus modulate endocannabinoid signalling. In the present review, the preclinical evidence that these enzymes are good targets for development of novel therapies for anxiety and depression are discussed from a practical, rather than mechanistic, point of view. It is concluded that the preclinical data are promising, albeit tempered by problems of tolerance as well as effects upon learning and memory for irreversible monoacylglycerol lipase inhibitors, and limited by a focus upon male rodents alone. Clinical data so far has been restricted to safety studies with inhibitors of anandamide hydrolysis and a hitherto unpublished study on such a compound in elderly patients with major depressive disorders, but under the dose regimes used, they are well tolerated and show no signs of "cannabis-like" behaviours.

  • 248.
    Fowler, Christopher J.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Transport of endocannabinoids across the plasma membrane and within the cell2013Ingår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 280, nr 9, s. 1895-1904Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Endocannabinoids are readily accumulated from the extracellular space by cells. Although their uptake properties have the appearance of a process of facilitated diffusion, it is by no means clear as to whether there is a plasma membrane transporter dedicated to this task. Intracellular carrier proteins that shuttle the endocannabinoid anandamide from the plasma membrane to its intracellular targets such as the metabolic enzyme, fatty acid amide hydrolase, have been identified. These include proteins with other primary functions, such as fatty-acid-binding proteins and heat shock protein70, and possibly a fatty acid amide hydrolase-like anandamide transporter protein. Thus, anandamide uptake can be adequately described as a diffusion process across the plasma membrane followed by intracellular carrier-mediated transport to effector molecules, catabolic enzymes and sequestration sites, although it is recognized that different cells are likely to utilize different mechanisms of endocannabinoid transport depending upon the utility of the endocannabinoid for the cell in question.

  • 249. Friberg, Leif
    et al.
    Rosenqvist, Marten
    Lindgren, Arne
    Terent, Andreas
    Norrving, Bo
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    High prevalence of atrial fibrillation among patients with ischemic stroke2014Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 45, nr 9, s. 2599-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Purpose-Atrial fibrillation (AF) is a common cause of devastating but potentially preventable stroke. Estimates of the prevalence of AF among patients with stroke vary considerably because of difficulties in detection of intermittent, silent AF. Better recognition of AF in this patient group may help to identify and offer protection to individuals at risk. Our aim was to determine the nationwide prevalence of AF among patients with ischemic stroke, as well as their use of oral anticoagulation. Methods-Cross-sectional study of unselected patients in cross-linked nationwide Swedish health registers. All 94 083 patients with a diagnosis of ischemic stroke in the nationwide stroke register Riks-Stroke between 2005 and 2010 were studied. Information about previously diagnosed AF, and comorbidity, was obtained from the nationwide Patient Register and cross-referenced with the national Drug Register containing data on all dispensed pharmacological prescriptions in Sweden. Results-Combination of data from Riks-Stroke and from the Patient Register showed that 31 428 (33.4%) patients with ischemic stroke had previously known, or newly diagnosed, AF. Of those, only 16.2% had received warfarin in a pharmacy within 6 months before stroke onset. After hospital discharge, only 35.0% of the survivors received warfarin within the first 3 months after discharge. The likelihood for underlying AF was strongly correlated to the CHA(2)DS(2)-VASC score, which is a point based scheme for assessment of stroke risk in AF but which also predicts likelihood of AF. In this scheme points are given for age, previous stroke or transient ischemic attack, hypertension, heart failure, diabetes, vascular disease and female sex. Conclusions-Access to nationwide register data shows that AF is more common among patients with ischemic stroke than those previously reported. Few patients with stroke and AF had anticoagulant treatment before the event, and few got it after the event. CHA(2)DS(2)-VASc could be a useful monitoring tool to intensify efforts to diagnose AF among patients with cryptogenic stroke.

  • 250.
    Fytagoridis, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Deep brain stimulation of the posterior subthalamic area in the treatment of movement disorders2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: The posterior subthalamic area (PSA) is essentially composed of the caudal Zona incerta and the prelemniscal radiation. Subthalamotomy in the PSA was renowned for its effectiveness in alleviating movement disorders and particularly tremor. The modern literature on DBS of this area is limited, but promising results have been presented for Parkinson’s disease (PD), essential tremor (ET) and other movement disorders.  

    Aim: To evaluate the safety of PSA DBS with emphasis on the panorama of side effects, the distribution of stimulation-induced side effects and the effects of PSA DBS on verbal fluency. To evaluate the therapeutic effect of PSA DBS on less common forms of tremor, tremor-dominant PD, and concerning the long-term results in ET.

    Method: 40 patients were evaluated regarding side effects of the procedure. 28 patients with ET were analyzed for stimulation-induced side effects in a standardized manner. The locations of the contacts that caused stimulation-induced side effects were plotted on atlas slides. A 3-D model of the area was created based on these slides. Verbal fluency was analyzed in 17 patients with ET before surgery, after 3 days and finally after 1 year. Five patients with less common forms of tremor and 18 with ET were evaluated according to the ETRS at baseline and one year or 3-5 years after surgery, respectively. 14 patients with mainly unilateral tremor-dominant PD were evaluated a mean of 18 months after surgery according to the motor part of UPDRS.

    Results: PSA DBS was associated with few serious side-effects, but a transient and mild postoperative dysphasia was found in 22.5% of the patients. There was a slight transient decline in the performance on verbal fluency tests immediately after surgery. Visualization of the contacts causing stimulation-induced side effects showed that identical responses can be elicited from various points in the PSA and its vicinity. The effect on the less common forms of tremor was excellent except for neuropathic tremor where the effect was moderate. A pronounced and sustained microlesional effect was seen for some of the patients. After a mean of 4 years with unilateral PSA DBS the total ETRS score was improved by 52.4%, tremor by 91.8% and hand function by 78.0% in the patients with ET. There was no increase in the stimulation strength over time. In PD, the scores improved 47.7% for contralateral UPDRS III. Contralateral tremor, rigidity, and bradykinesia improved by 82.2%, 34.3%, and 26.7%, respectively.

    Conclusions: PSA DBS generally seem to be a safe procedure, but it may be associated with transient declines of verbal fluency. There was no clear somatotopic pattern with regard to stimulation-induced side effects in the PSA. PSA DBS can alleviate tremor regardless of the etiology. The long-term effects in ET were favorable when compared to our previous results of Vim DBS. The effect on Parkinsonian tremor was satisfying, however, the reductions of rigidity and bradykinesia were less compared to previous studies of PSA DBS for PD.

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