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  • 801.
    Zarrinkoob, Laleh
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Cerebral blood flow distribution, collateral function and pulsatility in healthy and in patients with symptomatic carotid stenosis : a magnetic resonance imaging approach2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: For the detection and treatment of early cerebral vascular disease it is of paramount importance to first understand the normal physiology of the cerebral vasculature, and subsequently, to understand how and when pathology can develop from that. This is especially important as the population above 65 years of age is increasing and aging itself is an established risk factor for the development of cerebral vascular disease. This, however, is not always an easy task, since there is a subtle balance and overlap between age-related physiological and pathophysiological changes in the arterial system. Atherosclerotic changes that lead to the development of carotid artery stenosis are responsible for about one fifth of all ischemic strokes. Today, the current state of evidence and the algorithm for carotid revascularization is mainly focused on the degree of carotid stenosis and not on its impact on cerebral hemodynamics. One reason for this is the lack of a non-invasive method, that allows for repeated investigations and provides accurate and reliable results to study cerebral hemodynamic changes. The overall aim of this thesis was to explore and develop a comprehensive approach to investigate the cerebral blood flow distribution, collateral function and pulsatility in healthy subjects and in patients with symptomatic carotid stenosis using a phase-contrast magnetic resonance imaging (PCMRI) platform. The thesis is based on four scientific papers (papers I—IV). 

    Methods: In papers I and II, 49 healthy young (mean 25 years) and 45 healthy elderly (mean 71 years) subjects were included. 2D PCMRI was used to assess cerebral blood flow rate (BFR), pulsatility index (PI) and dampening factor (DF) in 15 cerebral arteries and in the ophthalmic arteries (OA). Thirty-eight patients (mean 72 years) with symptomatic carotid stenosis were included in paper III. Nineteen of these patients (mean 71 years) underwent carotid endarterectomy (CEA) (paper IV). 4D PCMRI was used for BFR assessment in papers III and IV. BFR, its distribution and collateral routes, was measured in 17 cerebral arteries and in the OA. The BFR on ipsilateral side (with symptomatic stenosis) was compared to the contralateral side (papers III and IV). BFR laterality was defined as contralateral BFR minus ipsilateral BFR in paired arteries and, BFR was compared before and after CEA (paper IV).

    Results: On average, in healthy subjects, 72% of the total cerebral blood flow (tCBF) was distributed through the anterior circulation and 28% through the posterior circulation. The distribution was symmetrical and not affected by age, sex, or brain volume (paper I). Aging resulted in lower BFRs, increased pulsatility and reduced dampening capacity in cerebral arteries. Anatomical variations in the circle of Willis resulted in an asymmetrical distribution of blood flow (papers I and II). In patients with carotid stenosis, a lower BFR was found in the internal carotid artery (ICA) and its branches on the ipsilateral side. The anterior cerebral artery territory was bilaterally, primarily, supplied by the contralateral ICA. In addition to the supply through the ICA, the middle cerebral artery (MCA) territory on the ipsilateral side was secured by collateral supply from the OA and the posterior communicating arteries, seen as retrograde flow in those arteries. Despite these compensations, BFR in ipsilateral side MCA was lower, and this laterality was more pronounced in patients with severe carotid stenosis (≥70%). After CEA, the distribution of BFR going into the cerebral arteries was found to be symmetrically distributed. Total CBF increased postoperatively in patients with collateral recruitment preoperatively (n=9). The BFR laterality in MCA observed prior to CEA, was found only in the group of patients with collateral recruitment preoperatively (paper IV). The degree of stenosis did not differ between the groups with and without collateral recruitment. 

    Conclusions: This thesis provides a new and comprehensive approach to mapping and quantifying normal cerebral blood flow and pulsatility. By presenting the distribution of tCBF going into cerebral arteries, instead of using absolute values, the effect of age could be neutralized and the results can be applicable when describing healthy cerebral blood flow, regardless of age. 4D PCMRI made it possible to describe the altered blood flow distribution and collateral ranking in patients with carotid stenosis prior to CEA and its normalization after the procedure. Our findings highlight the importance of BFR quantification for understanding cerebral hemodynamics in patients with carotid stenosis. 4D PCMRI technique is a promising clinical tool for investigations of cerebral hemodynamics in patients with stroke.

  • 802.
    Zarrinkoob, Laleh
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Quantification and mapping of cerebral hemodynamics before and after carotid endarterectomy: a 4D PCMRI studyManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background and purpose: A carotid stenosis can have a profound impact on the cerebral hemodynamics that cannot be inferred from the degree of stenosis by itself. We aimed to quantify and map the distribution of blood flow rate (BFR) in cerebral arteries before and after carotid endarterectomy (CEA), using four-dimensional phase-contrast magnetic resonance imaging (4D PCMRI).

    Methods: Nineteen patients (71±6 years, 2 women) with symptomatic carotid stenosis (≥50%)undergoing CEA were investigated using 4D PCMRI before and after surgery. BFR was measured in 17 cerebral arteries and in the ophthalmic arteries (OA). Collateral recruitment through the anterior and posterior communicating arteries, OA and the leptomeningeal arterial route was identified and quantified. BFR laterality was described as contralateral BFR minus ipsilateral BFR in paired arteries.

    Results: Total cerebral blood flow increased by 15% (p<0.01) after CEA. On the ipsilateral side, increased BFR was found after CEA in internal carotid artery (ICA) (246±62mL/min vs. 135±80mL/min; p<0.001), anterior cerebral artery (87±mL/min vs. 38±58mL/min; p<0.01) and middle cerebral artery (MCA) (149±43mL/min vs. 119±34mL/min; p<0.01), resulting in a postoperative BFR distribution without signs of laterality. In patients with preoperatively recruited collaterals (n=9), BFR laterality was found in MCA before, but not after, CEA (p<0.01). This laterality was not found in patients without collateral recruitment (n=10) (p=0.2). The degree of stenosis did not differ between the groups with vs. without collateral recruitment (p=0.85). 

    Conclusion: 4D PCMRI is a useful technique to quantify cerebral hemodynamic changes seen in patients with carotid stenosis before and after CEA. MCA laterality, seen in patients with collateral recruitment before CEA, pointed towards a hemodynamic disturbance in MCA territory for those patients. This study introduces a new and non-invasive way to evaluate cerebral hemodynamics due to carotid stenosis prior to and after CEA.

  • 803. Zetterberg, H.
    et al.
    Winblad, B.
    Bernick, C.
    Yaffe, K.
    Majdan, M.
    Johansson, G.
    Newcombe, V.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Sharp, D.
    Tenovuo, O.
    Blennow, K.
    Head trauma in sports - clinical characteristics, epidemiology and biomarkers2019Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 285, nr 6, s. 624-634Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Traumatic brain injury (TBI) is clinically divided into a spectrum of severities, with mild TBI being the least severe form and a frequent occurrence in contact sports, such as ice hockey, American football, rugby, horse riding and boxing. Mild TBI is caused by blunt nonpenetrating head trauma that causes movement of the brain and stretching and tearing of axons, with diffuse axonal injury being a central pathogenic mechanism. Mild TBI is in principle synonymous with concussion; both have similar criteria in which the most important elements are acute alteration or loss of consciousness and/or post-traumatic amnesia following head trauma and no apparent brain changes on standard neuroimaging. Symptoms in mild TBI are highly variable and there are no validated imaging or fluid biomarkers to determine whether or not a patient with a normal computerized tomography scan of the brain has neuronal damage. Mild TBI typically resolves within a few weeks but 10-15% of concussion patients develop postconcussive syndrome. Repetitive mild TBI, which is frequent in contact sports, is a risk factor for a complicated recovery process. This overview paper discusses the relationships between repetitive head impacts in contact sports, mild TBI and chronic neurological symptoms. What are these conditions, how common are they, how are they linked and can they be objectified using imaging or fluid-based biomarkers? It gives an update on the current state of research on these questions with a specific focus on clinical characteristics, epidemiology and biomarkers.

  • 804. Zhao, Charlie W.
    et al.
    Daley, Mark J.
    Pruszynski, J. Andrew
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Dept. of Computer Science, Western University, London, Ontario, Canada; Brain and Mind Institute, Western University, London, Ontario, Canada; Dept. of Physiology and Pharmacology, Western University, London, Ontario, Canada; Dept. of Psychology, Western University, London, Ontario, Canada; Robarts Research Institute, Western University, London, Ontario, Canada.
    Neural network models of the tactile system develop first-order units with spatially complex receptive fields2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 6, artikel-id e0199196Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    First-order tactile neurons have spatially complex receptive fields. Here we use machine-learning tools to show that such complexity arises for a wide range of training sets and network architectures. Moreover, we demonstrate that this complexity benefits network performance, especially on more difficult tasks and in the presence of noise. Our work suggests that spatially complex receptive fields are normatively good given the biological constraints of the tactile periphery.

  • 805. Zhuravleva, Z. D.
    et al.
    Lebedeva, A. V.
    Volnova, A. B.
    Mukhina, I. V.
    Druzin, Michael Ya.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    The effect of glycine microinjections in the medial preoptic area of the hypothalamus on the sexual behavior of male rats2015Ingår i: Neurochemical Journal, ISSN 1819-7124, Vol. 9, nr 2, s. 141-145Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The mechanisms that underlie the early loss of the male reproductive function are still unknown. Therefore, investigation of this problem is an important task. The medial preoptic nucleus takes part in the regulation of sexual behavior; however, the role of glycine transmission in this nucleus has not yet been studied. Our study focuses on these questions.

  • 806. Zrinzo, Ludvic
    et al.
    Akram, Harith
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, Unit Funct Neurosurg, London WC1N 3BG, England.
    Comment on "Appropriate MRI sequences are required to accurately determine lead location after deep brain stimulation surgery"2014Ingår i: Journal of clinical neuroscience, ISSN 0967-5868, E-ISSN 1532-2653, Vol. 21, nr 12, s. 2257-2258Artikel i tidskrift (Refereegranskat)
  • 807. Zrinzo, Ludvic
    et al.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Deep brain stimulation for dystonia2014Ingår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 120, nr 6, s. 1496-1496Artikel i tidskrift (Refereegranskat)
  • 808.
    Zrinzo, Ludvic
    et al.
    UCL, UCL Inst Neurol, Unit Funct Neurosurg, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
    Foltynie, Thomas
    UCL, UCL Inst Neurol, Unit Funct Neurosurg, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
    Limousin, Patricia
    UCL, UCL Inst Neurol, Unit Funct Neurosurg, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Image-verified deep brain stimulation reduces risk and cost with no apparent impact on efficacy2012Ingår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 27, nr 12, s. 1585-1586Artikel i tidskrift (Refereegranskat)
  • 809. Zrinzo, Ludvic
    et al.
    Foltynie, Thomas
    Limousin, Patricia
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Deep brain stimulation and hemorrhage RESPONSE2012Ingår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 116, nr 4, s. 930-932Artikel i tidskrift (Refereegranskat)
  • 810. Zrinzo, Ludvic
    et al.
    Foltynie, Thomas
    Limousin, Patricia
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review Clinical article2012Ingår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 116, nr 1, s. 84-94Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Object. Hemorrhagic complications carry by far the highest risk of devastating neurological outcome in functional neurosurgery. Literature published over the past 10 years suggests that hemorrhage, although relatively rare, remains a significant problem. Estimating the true incidence of and risk factors for hemorrhage in functional neurosurgery is a challenging issue. Methods. The authors analyzed the hemorrhage rate in a consecutive series of 214 patients undergoing image-guided deep brain stimulation (DBS) lead placement without microelectrode recording (MER) and with routine postoperative MR imaging lead verification. They also conducted a systematic review of the literature on stereotactic ablative surgery and DBS over a 10-year period to determine the incidence and risk factors for hemorrhage as a complication of functional neurosurgery. Results. The total incidence of hemorrhage in our series of image-guided DBS was 0.9%: asymptomatic in 0.5%, symptomatic in 0.5%, and causing permanent deficit in 0.0% of patients. Weighted means calculated from the literature review suggest that the overall incidence of hemorrhage in functional neurosurgery is 5.0%, with asymptomatic hemorrhage occurring in 1.9% of patients, symptomatic hemorrhage in 2.1% and hemorrhage resulting in permanent deficit or death in 1.1%. Hypertension and age were the most important patient-related factors associated with an increased risk of hemorrhage. Risk factors related to surgical technique included use of MER, number of MER penetrations, as well as sulcal or ventricular involvement by the trajectory. The incidence of hemorrhage in studies adopting an image-guided and image-verified approach without MER was significantly lower than that reported with other operative techniques (p < 0.001 for total number of hemorrhages, p < 0.001 for asymptomatic hemorrhage, p < 0.004 for symptomatic hemorrhage, and p = 0.001 for hemorrhage leading to permanent deficit; Fisher exact test). Conclusions. Age and a history of hypertension are associated with an increased risk of hemorrhage in functional neurosurgery. Surgical factors that increase the risk of hemorrhage include the use of MER and sulcal or ventricular incursion. The meticulous use of neuroimaging-both in planning the trajectory and for target verification-can avoid all of these surgery-related risk factors and appears to carry a significantly lower risk of hemorrhage and associated permanent deficit. (DOI: 10.3171/2011.8.JNS101407)

  • 811. Zrinzo, Ludvic
    et al.
    Foltynie, Thomas
    Limousin, Patricia
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Response to: Editorial - Functional neurosurgery and hemorrhage2012Ingår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 116, nr 1, s. 83-83Artikel i tidskrift (Refereegranskat)
  • 812. Zrinzo, Ludvic
    et al.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Conclusions should be supported by the data presented2013Ingår i: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 27, nr 4, s. 545-546Artikel i tidskrift (Refereegranskat)
  • 813. Zrinzo, Ludvic
    et al.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Errors of Image Coregistration may Necessitate Intraoperative Refinement in Functional Neurosurgery2013Ingår i: J NEUROL SURG PART A, ISSN 2193-6315, Vol. 74, nr 5, s. 335-336Artikel i tidskrift (Refereegranskat)
  • 814. Zrinzo, Ludvic
    et al.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. UCL Institute of Neurology, University College London, London, United Kingdom.
    Hyam, Jonathan A.
    Foltynie, Thomas
    Limousin, Patricia
    A paradigm shift toward MRI-guided and MRI-verified DBS surgery2016Ingår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 124, nr 4, s. 1135-1137Artikel i tidskrift (Refereegranskat)
  • 815. Zrinzo, Ludvic
    et al.
    Zrinzo, Laurence V.
    Massey, Luke A.
    Thornton, John
    Parkes, Harold G.
    White, Mark
    Yousry, Tarek A.
    Strand, Catherine
    Revesz, Tamas
    Limousin, Patricia
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Holton, Janice L.
    Targeting of the pedunculopontine nucleus by an MRI-guided approach: a cadaver study2011Ingår i: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 118, nr 10, s. 1487-1495Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Laboratory evidence suggests that the pedunculopontine nucleus (PPN) plays a central role in the initiation and maintenance of gait. Translational research has led to reports on deep brain stimulation (DBS) of the rostral brainstem in parkinsonian patients. However, initial clinical results appear to be rather variable. Possible factors include patient selection and the wide variability in anatomical location of implanted electrodes. Clinical studies on PPN DBS efficacy would, therefore, benefit from an accurate and reproducible method of stereotactic localization of the nucleus. The present study evaluates the anatomical accuracy of a specific protocol for MRI-guided stereotactic targeting of the PPN in a human cadaver. Imaging at 1.5 and 9.4 T confirmed electrode location in the intended region as defined anatomically by the surrounding fiber tracts. The spatial relations of each electrode track to the nucleus were explored by subsequent histological examination. This confirmed that the neuropil surrounding each electrode track contained scattered large neurons morphologically consistent with those of the subnucleus dissipatus and compactus of the PPN. The results support the accuracy of the described specific MR imaging protocol.

  • 816.
    Árnadóttir, Guðrún
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi. 1Occupational Therapy Unit, Grensás, Landspítali University Hospital, Reykjavík; 2Division of Occupational Therapy, Faculty of Health, University of Akureyri, Akureyri, Iceland.
    Löfgren, Britta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Fisher, Anne G
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Difference in impact of neurobehavioural dysfunction on Activities of Daily Living performance between right and left hemispheric stroke2010Ingår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 42, nr 10, s. 903-907Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To explore whether persons with right- and left-sided cerebrovascular accidents differ significantly in mean impact of neurobehavioural impairments on ability to perform activities of daily living. Design and subjects: Retrospective study of data from 215 persons (103 right-sided, 112 left-sided cerebrovascular accident). The Activities of daily living-focused Occupation-based Neurobehavioral Evaluation was used to evaluate ability on an activities of daily living scale and the impact of neurobehavioural impairment on ability on another scale. Methods: To control for possible differences in activities of daily living ability between groups, analysis of covariance, with activities of daily living ability as a covariate, was used to test for a significant difference in impact of neurobehavioural impairments on activities of daily living ability between groups. Results: Expected moderate correlation (r=-0.57) was obtained between activities of daily living ability and neurobehavioural impact measures, and there was no difference in mean neurobehavioural impact measures between groups (F [1, 212] = 2.910,p = 0.090). Conclusion: This study is the first: to explore directly the impact of neurobehavioural impairment on activities of daily living ability. While persons with right-sided and left-sided cerebrovascular accidents may differ in type of neurobehavioural impairments, direct evaluation of the impact of such impairments on activities of daily living ability reveals no difference between groups.

  • 817.
    Ängquist, Karl-Axel
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Human skeletal muscle fibre structure: effects of physical training and arterial insufficiency1978Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
  • 818.
    Ågren Wilsson, A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Roslin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, LO
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Bergenheim, AT
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Malm, J
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Intracerebral microdialysis and CSF hydrodynamics in idiopathic adult hydrocephalus syndrome2003Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 74, nr 2, s. 217-221Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In idiopathic adult hydrocephalus syndrome (IAHS), a pathophysiological model of "chronic ischaemia" caused by an arteriosclerotic process in association with a CSF hydrodynamic disturbance has been proposed. OBJECTIVE: To investigate whether CSF hydrodynamic manipulation has an impact on biochemical markers related to ischaemia, brain tissue oxygen tension (PtiO(2)), and intracranial pressure. METHODS: A microdialysis catheter, a PtiO(2) probe, and an intracerebral pressure catheter were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. A subcutaneous microdialysis probe was used as reference. Intracranial pressure and intracerebral PtiO(2) were recorded continuously. Samples were collected for analysis between 2 and 4 pm on day 1 (baseline) and at the same time on day 2, two to four hours after a lumbar CSF hydrodynamic manipulation. The concentrations of glucose, lactate, pyruvate, and glutamate on day 1 and 2 were compared. RESULTS: After CSF drainage, there was a significant rise in the intracerebral concentration of lactate and pyruvate. The lactate to pyruvate ratio was increased and remained unchanged after drainage. There was a trend towards a lowering of glucose and glutamate. Mean intracerebral PtiO(2) was higher on day 2 than on day 1 in six of eight patients. CONCLUSIONS: There is increased glucose metabolism after CSF drainage, as expected in a situation of postischaemic recovery. These new invasive techniques are promising tools in the future study of the pathophysiological processes in IAHS.

  • 819.
    Ågren-Wilsson, A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Lekman, A
    Sjöberg, W
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Rosengren, L
    Blennow, K
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus2007Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 116, nr 5, s. 333-339Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND To evaluate cerebrospinal fluid (CSF) markers for neuronal degeneration and demyelination in idiopathic normal pressure hydrocephalus (INPH), subcortical arteriosclerotic encephalopathy (SAE), and neurologically healthy subjects.

    METHODS Lumbar CSF concentrations of sulfatide, neurofilament protein light (NFL), total-tau (T-tau), hyperphosphorylated tau (P-tau), and beta-amyloid(1-42) (Abeta42) were analyzed in 62 INPH patients, 26 SAE patients, and 23 neurologically healthy controls. In INPH patients, samples before and after shunt surgery were analysed.

    RESULTS The CSF concentration of NFL was elevated in INPH and SAE compared with the controls, and levels of T-tau, P-tau, and Abeta42 were lower in INPH compared with SAE and controls. No difference was seen for sulfatide. All markers except Abeta42 were significantly elevated after shunt surgery.

    CONCLUSIONS The most striking finding was the power of the combined pattern of NFL, P-tau, and Abeta42 in distinguishing between the clinical diagnoses of INPH, SAE, and neurologically healthy elderly.

  • 820.
    Ågren-Wilsson, Aina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, L-O D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Brain energy metabolism and intracranial pressure in idiopathic adult hydrocephalus syndrome2005Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 76, nr 8, s. 1088-1093Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The symptoms in idiopathic adult hydrocephalus syndrome (IAHS) are consistent with pathology involving the periventricular white matter, presumably reflecting ischaemia and CSF hydrodynamic disturbance. OBJECTIVE: To investigate whether a change in intracranial pressure (ICP) can affect energy metabolism in deep white matter. METHODS: A microdialysis catheter, a brain tissue oxygen tension probe, and an ICP transducer were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. ICP and intracerebral Ptio2 were recorded continuously during lumbar CSF constant pressure infusion test. ICP was raised to pressure levels of 35 and 45 mm Hg for 10 minutes each, after which CSF drainage was undertaken. Microdialysis samples were collected every three minutes and analysed for glucose, lactate, pyruvate, and glutamate. RESULTS: When raising the ICP, a reversible drop in the extracellular concentrations of glucose, lactate, and pyruvate was found. Comparing the values during baseline to values at the highest pressure level, the fall in glucose, lactate, and pyruvate was significant (p < 0.05, Wilcoxon sign rank). There was no change in glutamate or the lactate to pyruvate ratio during ICP elevation. Ptio2 did not decrease during ICP elevation, but was significantly increased following CSF drainage. CONCLUSIONS: Raising intracranial pressure induces an immediate and reversible change in energy metabolism in periventricular white matter, without any sign of ischaemia. Theoretically, frequent ICP peaks (B waves) over a long period could eventually cause persisting axonal disturbance and subsequently the symptoms noted in IAHS.

  • 821. Åkerstedt, Torbjörn
    et al.
    Nordin, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Alfredsson, Lars
    Westerholm, Peter
    Kecklund, Göran
    Predicting changes in sleep complaints from baseline values and changes in work demands, work control, and work preoccupation - The WOLF-project2012Ingår i: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 13, nr 1, s. 73-80Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Study objective: Stress as a cause of disturbed sleep is often taken for granted, but the longitudinal evidence is limited. The aim of this study was to evaluate new cases of poor sleep as a function of changes in reported work demands, work control, and work preoccupation. Methods: Longitudinal study of change with measures occurring twice within a 5-year interval during a period when the prevalence of impaired sleep was increasing in Sweden. The sample of companies was taken from northern Sweden (Norrland) and included 3637 individuals from the "WOLF Norrland" longitudinal cohort, collected through company health services. Measurement and results: During the measurement period, 16% of those studied developed new cases of impaired sleep. Logistic regressions adjusted for demographics, work environment factors, and disturbed sleep at T1 period one showed a significant increase in new cases for high work demands and high work preoccupation (OR = 1.37; Ci = 1.09-1.72 and OR = 1.80; CI = 1.42-2.28, respectively). The analysis of change in the predictors showed effects of a change from low to high work demands (OR = 1.39; Ci = 1.00-1.95) on new cases of impaired sleep. Consistent high work demands (high at both points) showed a similar increase (OR = 1.49; Ci = 1.06-2.11) but no effect was seen for reduced demands. Change in work preoccupation yielded stronger effects with OR = 2.47 (1.78-2.47) for increased work preoccupation and OR = 3.79 (2.70-5.31) for consistent high work preoccupation. Also, a reduction in work preoccupation was associated with a reduction in new cases of disturbed sleep. Control at work was not related to sleep. Stratification with respect to gender mainly led to fewer significant results (particularly for women) due to larger confidence intervals. Conclusions: It was concluded that self-reported work preoccupation predicts subsequent impairment of sleep and that increased preoccupation is associated with new cases of impaired sleep. Similar, but weaker, results were obtained for work demands. (C) 2011 Elsevier B.V. All rights reserved.

  • 822.
    Åsberg, Signild
    et al.
    Department of Medical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.
    Eriksson, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Henriksson, Karin M
    Department of Medical Sciences, Uppsala University, SE-75185 Uppsala, Sweden; AstraZeneca R&D, Mölndal, Sweden.
    Terént, Andreas
    Department of Medical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.
    Warfarin-Associated Intracerebral Hemorrhage After Ischemic Stroke2014Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 45, nr 7, s. 2118-2120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: The aim was to investigate the risk of intracerebral hemorrhage (ICH) in patients with ischemic stroke taking warfarin and whether this risk changed over time.

    METHODS: Between 2001 and 2008, the Swedish Stroke Register registered 12 790 patients with ischemic stroke discharged on warfarin. The patients was studied in two 4-year periods (inclusion 2001-2004: follow-up until 2005 and inclusion 2005-2008: follow-up until 2009) for which rates of subsequent ICH were calculated. Adjusted hazard ratios, comparing the second period with the first period, were estimated in Cox regression models.

    RESULTS: Of 6039 patients, 58 patients (1.0%) in the first period and 69 of 6751 patients (1.0%) in the second period had subsequent ICH. Annual rates of ICH ranged from 0.37% in the first period to 0.39% in the second period (adjusted hazard ratio, 1.04; 95% confidence interval, 0.73-1.48).

    CONCLUSIONS: In this nationwide study, the risk of warfarin-associated ICH among ischemic stroke patients was low and did not change during the 2000s.

  • 823. Åström, Mattias
    et al.
    Tripoliti, Elina
    Martinez-Torres, Irene
    Zrinzo, Ludvic U
    Limousin, Patricia
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Wårdell, Karin
    Patient-specific models and simulations of deep brain stimulation for postoperative follow-up2009Ingår i: World Congress on Medical Physics and Biomedical Engineering September 7 - 12, 2009 Munich, Germany: Vol. 25/9 Neuroengineering, Neural Systems, Rehabilitation and Prosthetics / [ed] Dössel, Olaf; Schlegel, Wolfgang C., Springer , 2009, s. 331-334Konferensbidrag (Övrigt vetenskapligt)
  • 824.
    Ögren, Joachim
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Serious hemorrhage and secondary prevention after stroke and TIA2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: The number of stroke survivors is growing worldwide, and these patients have an increased risk of new vascular events and death. This risk decreases with secondary treatment medications recommended in guidelines. However, the characteristics of unselected stroke patients differ from patients included in randomized controlled trials (RCTs). Thus, the efficacy of these treatments based on RCT results may not be directly transferable to the patients treated in clinical practice. A treatment may be associated with a higher risk of serious side-effects or less benefit than expected:1) Antithrombotic treatment increases the risk of a serious hemorrhage, a risk that is not well studied in an unselected population with older age and more comorbidities; 2) Treatment of modifiable risk factors after a stroke can be improved. Many patients do not reach treatment targets, which indicates a need for strategies to improve secondary prevention and increase treatment benefit.It is therefore essential to evaluate recommended treatments through studies in a real-world setting.

    Aims: The aims of this thesis were to assessincidence, temporal trends, effect on mortality, and factors associated with an increased risk of a serious hemorrhage after ischemic stroke (IS) or transient ischemic attack (TIA); andif a nurse-led, telephone-based intervention including medical titration could improve modifiable risk factors in patients after stroke or TIA.

    Methods: In paper I, all patients registered with an IS in the national stroke register Riksstroke during 1998–2009 were studied. The register was combined with the In-Patient Register and a diagnosis of intracranial haemorrhage (ICrH) within 1 year after IS was identified. In paper II, any diagnosis of serious hemorrhage was identified during follow-up up to 2015 in all patients with an IS or TIA diagnosis, 2010–2013, at Östersund hospital. The incidences of ICrH (papers I and II) and all serious hemorrhages (paper II) were calculated. Kaplan–Meier analysis was used to assess any temporal trend in paper I and if a serious hemorrhage affected survival in study II. Cox regression analysis was used in both studies I and II to assess any factor associated with hemorrhage.

    In the randomized controlled NAILED stroke trial, all patients with acute stroke or TIA treated at Östersund hospital during 2010–2013 were screened for participation. Patients whose condition permitted a telephone-based follow-up were randomized to either a control group with follow-up according to usual care or to an intervention group with a nurse-led, telephone-based follow-up including titration of medication. Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) were assessed at 1, 12, 24, and 36 months. We assessed the effect of the intervention on mean levels of BP and LDL-C and on the proportion of patients reaching treatment targets at 12 months (Study III) and at 36 months (Study IV). Study III also assessed for interactions between group allocation and measurement levels at baseline with BP and LDL-C at the 12-month follow-up. Study IV also explored temporal trends.

    Results: The risk of an ICrH was 1.97% per year at risk, within the first year after IS,  and 0.85% excluding the first 30 days. Between 1998 and 2009, the risk of an ICrH increased during the first 30 days after an IS but decreased during days 31–365. The risk of a serious hemorrhage was 2.48% per year at risk in paper II. It was more common in elderly. The incidence rate was higher in patients discharged with AP compared with RCTs. A hemorrhage increased the risk of death in patients with good functional status but did not affect the already high mortality in patients with impaired functional status. Male sex and previous ICrH were associated with an increased risk of ICrH during the first year after IS, thrombolytic treatment, atrial fibrillation and warfarin were associated with an increased risk in the acute phase. A previous diagnosis of hypertension was associated with an increased risk of all serious hemorrhages. 

    The NAILED trial intervention group had a significantly lower mean systolic BP (SBP), diastolic BP (DBP), and LDL-C at 12 and 36 months. The mean SBP at 36 months was 128.1 mmHg (95% confidence interval (CI): 125.8–130.5) in the intervention group, 6.1 mmHg (95% CI: 3.6–8.6; p<0.001) lower than the control group. The interaction analysis at 12 months showed that the effect of the intervention was confined to patients whose values were above the respective targets at baseline and therefore had their medication adjusted. At 36 months, a significantly higher proportion of patients in the intervention group reached treatment targets for SBP, DBP, and LDL-C. The mean differences and differences in proportions reaching treatment target for BP increased during the 36 months of follow-up.

    Conclusion: A serious hemorrhage after an IS or TIA is fairly common. It is more common in elderly and patients with impaired functional status. The incidence is higher in patients discharged with AP compared with RCTs. A serious hemorrhage could affect survival in patients with good functional status. The nurse-led, telephone-based intervention including medical titration used in the NAILED stroke trial improved risk factor levels after stroke and TIA, and more patients reached treatment targets. The effect increased over time. 

  • 825.
    Ögren, Joachim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Irewall, Anna-Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Söderström, Lars
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Long-term, telephone-based follow-up after stroke and TIA improves risk factors: 36-month results from the randomized controlled NAILED stroke risk factor trial2018Ingår i: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 18, artikel-id 153Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Strategies are needed to improve adherence to the blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) level recommendations after stroke and transient ischemic attack (TIA). We investigated whether nurse-led, telephone-based follow-up that included medication titration was more efficient than usual care in improving BP and LDL-C levels 36 months after discharge following stroke or TIA.

    Methods: All patients admitted for stroke or TIA at Ostersund hospital that could participate in the telephone-based follow-up were considered eligible. Participants were randomized to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C were measured one month after discharge and yearly thereafter. Intervention group patients who did not meet the target values received additional follow-up, including lifestyle counselling and medication titration, to reach their treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L). The primary outcome was the systolic BP level 36 months after discharge.

    Results: Out of 871 randomized patients, 660 completed the 36-month follow-up. The mean systolic and diastolic BP values in the intervention group were 128.1 mmHg (95% CI 125.8-1305) and 75.3 mmHg (95% CI 73.8-76.9), respectively. This was 6.1 mmHg (95% CI 3.6-8.6, p < 0.001) and 3.4 mmHg (95% CI 1.8-5.1, p < 0.001) lower than in the control group. The mean LDL-C level was 22 mmol/L in the intervention group, which was 03 mmol/L (95% CI 0.2-0.5, p < 0.001) lower than in controls. A larger proportion of the intervention group reached the treatment goal for BP (systolic: 79.4% vs. 55.3%, p < 0.001; diastolic 90.3% vs. 77.9%, p < 0.001) as well as for LDL-C (69.3% vs. 48.9%, p < 0.001).

    Conclusions: Compared with usual care, a nurse-led telephone-based intervention that included medication titration after stroke or TIA improved BP and LDL-C levels and increased the proportion of patients that reached the treatment target 36 months after discharge.

  • 826.
    Ögren, Joachim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Irewall, Anna-Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Söderström, Lars
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Serious hemorrhages after ischemic stroke or TIA - Incidence, mortality, and predictors2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 4, artikel-id e0195324Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Data are lacking on the risk and impact of a serious hemorrhage on the prognosis after ischemic stroke (IS) or transient ischemic attack (TIA). We aimed to estimate the incidence of serious hemorrhage, analyze the impact on mortality, and identify predictors of hemorrhage after discharge from IS or TIA.

    Methods and findings: All patients admitted to Östersund Hospital for an IS or TIA in 2010–2013 were included (n = 1528, mean age: 75.1 years). Serious hemorrhages were identified until 31st December 2015. Incidence rates were calculated. The impact on mortality (stratified by functional level) was determined with Kaplan-Meier analysis. Non-parametric estimation under the assumption of competing risk was performed to assess the cumulative incidence and predictors of serious hemorrhages. The incidence rates of serious (n = 113) and intracranial hemorrhages (n = 45) after discharge from IS and TIA were 2.48% and 0.96% per year at risk, respectively. Patients with modified Rankin Scale (mRS) scores of 3–5 exhibited 58.9% mortality during follow-up and those with mRS scores of 0–2 exhibited 18.4% mortality. A serious hemorrhage did not affect mortality in patients with impaired functional status, but it increased the risk of death in patients with mRS scores of 0–2. Hypertension was associated with increased risk of serious hemorrhage.

    Conclusions: We found that, after discharge from an IS or TIA, serious hemorrhages were fairly common. Impairments in function were associated with high mortality, but serious hemorrhages only increased the risk of mortality in patients with no or slight disability. Improved hypertension treatment may decrease the risk of serious hemorrhage, but in patients with low functional status, poor survival makes secondary prevention challenging.

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