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  • 1.
    Andersson, Johanna
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Rosell, Michelle
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Kockum, Karin
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Lilja-Lund, Otto
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Soderstrom, Lars
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Prevalence of idiopathic normal pressure hydrocephalus: A prospective, population-based study2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 5, article id e0217705Article in journal (Refereed)
    Abstract [en]

    Background: Idiopathic normal pressure hydrocephalus (iNPH) causing gait impairment, dementia and urinary incontinence among the elderly, is probably under-diagnosed and under-treated. Despite being known since the 1960s, there is still a lack of prospective, population-based studies on the prevalence of iNPH. Such studies are warranted to minimize selection bias and estimate the true prevalence of the disease.

    Methods: The prevalence of iNPH was determined in a randomly selected sample of residents, aged 65 years and older, in the Swedish county of Jämtland. Out of 1,000 individuals invited to participate, 673 (67.3%) completed a questionnaire with seven questions on iNPH symptoms. A subgroup, with and without self-reported symptoms, participated in clinical and radiological evaluations and were diagnosed according to international guidelines. Measurement of cerebrospinal fluid opening pressure was not performed as it was considered too invasive.

    Results: Those who reported at least two symptoms in the questionnaire (n = 117) and 51 randomly selected individuals with 0–1 symptom participated in further examinations. Out of them, 25 individuals received the diagnosis probable iNPH according to American-European guidelines (except for the criterion of CSF opening pressure) corresponding to a prevalence of 3.7%. The prevalence of iNPH was four times higher among those aged 80 years and older (8.9%) than among those aged 65–79 years (2.1%) (p <0.001). The difference in prevalence between men (4.6%) and women (2.9%) was not significant (p = 0.24). When iNPH was diagnosed according to the Japanese guidelines the prevalence was 1.5%

    Conclusions: In this prospective, population-based study the prevalence of iNPH was 3.7% among individuals 65 years and older, and more common in the higher age group, 80 years and above. INPH should be increasingly recognized since it is a fairly common condition and an important cause of gait impairment and dementia among the elderly that can be effectively treated by shunt surgery.

  • 2.
    Andersson, Jörgen
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Rosell, M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Kockum, Karin
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderström, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Challenges in diagnosing normal pressure hydrocephalus: evaluation of the diagnostic guidelines2017In: eNeurologicalSci, ISSN 2405-6502, Vol. 7, p. 27-31Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the present diagnostic guidelines of idiopathic normal pressure hydrocephalus (iNPH) in a sample from the general population.

    Methods: A total of 168 individuals (93 females, 75 males), mean age 75 years (range 66-92) with and without symptoms of iNPH underwent a CT-scan of the brain, a neurological examination with assessment of the triad symptoms, i.e. gait disturbances, memory impairment and urgency incontinence. The participants were then diagnosed as "unlikely", "possible" and "probable" iNPH according to the American-European and the Japanese guidelines, respectively. Separately, a senior consultant in neurology diagnosed each patient based on the overall clinical picture.

    Results: Obtaining a diagnosis of "probable iNPH" was three times more likely according to the American-European guidelines (n = 35) compared to the Japanese guidelines (n = 11) or the neurologist (n = 11). The concordance was highest (Kappa = 0.69) between the Japanese guidelines and the neurologist.

    Conclusions: Considerable discrepancies were found when diagnosing iNPH according to two international guidelines and a neurologist, respectively. The Japanese guidelines, which include a minimum of two triad symptoms, were most concordant with the neurologist. As a step towards widely accepted, standardized diagnostic criteria, we suggest a revision of the current guidelines, preferably into one common diagnostic system.

  • 3.
    Andersson, Kennet
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Manchester, I. R.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cesarini, K. Giuliana
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Measurement of CSF dynamics with oscillating pressure infusion2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 128, no 1, p. 17-23Article in journal (Refereed)
    Abstract [en]

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

  • 4.
    Andrén, Kerstin
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wikkelsö, Carsten
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Agerskov, Simon
    Israelsson, Hanna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Hellström, Per
    Tullberg, Mats
    Long-term effects of complications and vascular comorbidity in idiopathic normal pressure hydrocephalus: a quality registry study2018In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 265, no 1, p. 178-186Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 5.
    Bergström, L.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Ögren, Joachim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Irewall, Anna-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Recurrent ischemic stroke in patients with diabetes mellitus - incidence, trend over time and predictors2015In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 39, p. 14-14Article in journal (Other academic)
  • 6.
    Bergström, Lisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Irewall, Anna-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Soderstrom, Lars
    Ögren, Joachim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    One-Year Incidence, Time Trends, and Predictors of Recurrent Ischemic Stroke in Sweden From 1998 to 2010 An Observational Study2017In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 48, no 8, p. 2046-Article in journal (Refereed)
    Abstract [en]

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

  • 7.
    Bergström, Lisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Irewall, Anna-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderström, Lars
    Ögren, Joachim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    One-year incidence, time trends, and predictors of recurrent ischemic stroke in Sweden from 1998-2010: An observational studyManuscript (preprint) (Other academic)
  • 8.
    de Flon, Pierre
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Gunnarsson, Martin
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderström, Lars
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Lindqvist, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Krauss, Wolfgang
    Dring, Ann
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bergman, Joakim
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab2016In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 87, no 2, p. 141-147Article in journal (Refereed)
    Abstract [en]

    Objective: To describe the effects of switching treatment from ongoing first-line injectable therapies to rituximab on inflammatory activity measured by MRI and levels of CSF neurofilament light chain (CSF-NFL) in a cohort of patients with clinically stable relapsing-remitting multiple sclerosis (RRMS).

    Method: Seventy-five patients with clinically stable RRMS treated with the first-line injectables interferon-β (IFN-β) and glatiramer acetate (GA) at 3 Swedish centers were switched to rituximab in this open-label phase II multicenter study. After a run-in period of 3 months, 2 IV doses of 1,000 mg rituximab were given 2 weeks apart followed by repeated clinical assessment, MRI, and CSF-NFL for 24 months.

    Results: The mean cumulated number of gadolinium-enhancing lesions per patient at months 3 and 6 after treatment shift to rituximab was reduced compared to the run-in period (0.028 vs 0.36, p = 0.029). During the first year after treatment shift, the mean number of new or enlarged T2 lesions per patient was reduced (0.01 vs 0.28, p = 0.004) and mean CSF-NFL levels were reduced by 21% (p = 0.01).

    Conclusions: For patients with RRMS, a treatment switch from IFN or GA to rituximab is associated with reduced inflammatory activity measured by MRI and CSF-NFL.

    Classification of evidence: This study provides Class IV evidence that rituximab has an equal or superior effect in reducing inflammatory activity in RRMS measured by MRI and CSF-NFL compared to first-line injectables during the first year after treatment shift.

  • 9.
    de Flon, Pierre
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Blennow, Kaj
    Söderström, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Zetterberg, Henrik
    Gunnarsson, Martin
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Department of Clinical Sciences, Karolinska Institute Danderyd Hospital, Stockholm, Sweden.
    Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial2019In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, no 5, p. 462-468Article in journal (Refereed)
    Abstract [en]

    Objective: The main objective of this study was to evaluate the axonal component neurofilament light protein (NFL) in plasma and cerebrospinal fluid (CSF) as an outcome measure in a clinical trial on disease-modifying treatments in multiple sclerosis.

    Materials and methods: Seventy-five patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) participating in the clinical trial "Switch-To RItuXimab in MS" (STRIX-MS) were switched to rituximab from first-line injectable therapy and then followed up for 2 years. Thirty patients from the extension trial (STRIX-MS extension), accepting repeated lumbar punctures, were followed up for an additional 3 years. Plasma and CSF samples were collected yearly during the follow-up. NFL concentration in plasma was measured by an in-house NF-light assay on the Simoa platform with a Homebrew kit. NFL concentration in CSF was measured by sandwich ELISA.

    Results: The mean levels of NFL, in both CSF and plasma, were low. The reduction of CSF-NFL was 25% during the first year of follow-up (from a mean of 471 [SD 393] to 354 [SD 174] pg/mL; P = 0.006) and was statistically significant. The corresponding reduction in plasma NFL was 18% (from 9.73 [SD 7.04] to 7.94 [SD 3.10] pg/mL; P = 0.055) and did not reach statistical significance.

    Conclusion: This study indicates that NFL in plasma is less sensitive as an endpoint in group comparisons than NFL in CSF. Given that plasma NFL is far easier to access, it is a promising and awaited method but further studies are needed to optimize the use in clinical trials.

  • 10.
    de Flon, Pierre
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Neurology, Östersund Hospital, Östersund, Sweden.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderström, Lars
    Gunnarsson, Martin
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Improved treatment satisfaction after switching therapy to rituximab in relapsing-remitting MS2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 9, p. 1249-1257Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: New disease-modifying treatment strategies in multiple sclerosis offer possibilities for individualised treatment. In this study, we evaluated patient-reported outcome measures before and after a switch in therapy from first-line injectable treatments to rituximab.

    METHOD: A total of 75 patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) receiving ongoing first-line injectable treatment at three Swedish centres had their treatment switched to rituximab in this open-label phase II multicentre study. Assessment of treatment satisfaction, patient-perceived impact of the disease on daily life, fatigue, cognitive symptoms and disease progression was performed 3 months before and at the time of the treatment shift and then for a subsequent 2-year period.

    RESULTS: The overall treatment satisfaction rating improved significantly from a mean of 4.8 (scale range: 1-7), while on injectable therapies, to a mean of 6.3 after 1 year of rituximab treatment ( p < 0.001). This improvement was sustained after 2 years. There was no significant change in scores for patient-perceived impact of disease, fatigue or disease progression.

    CONCLUSION: A shift in therapy from first-line injectables to rituximab in a cohort of clinically stable RRMS patients was followed by improved treatment satisfaction. This is clinically relevant as it may influence long-term adherence to immunomodulating therapy.

  • 11.
    de Flon, Pierre
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Soderstrom, L.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Gunnarsson, M.
    Svenningsson, A.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Sciences, Karolinska Institute, Stockholm, Sweden.
    Changes of cerebrospinal fluid cytokine profile as a result of switching from first line MS-therapies to rituximab2016In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, p. 622-622Article in journal (Refereed)
  • 12.
    de Flon, Pierre
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderström, Lars
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Dring, Ann
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Gunnarsson, Martin
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Dept of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm.
    Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192516Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate changes in the cerebrospinal fluid (CSF) immunological profile after treatment switch from first-line injectables to rituximab in patients with relapsing-remitting MS (RRMS), and to compare the profile in MS patients with healthy controls (HC).

    METHOD: Cerebrospinal fluid from 70 patients with clinically stable RRMS and 55 HC was analysed by a multiplex electrochemiluminescence method for a broad panel of cytokines and immunoactive substances before, and over a two-year period after, treatment switch to rituximab. After quality assessment of data, using a predefined algorithm, 14 analytes were included in the final analysis.

    RESULTS: Ten of the 14 analytes differed significantly in MS patients compared with HC at baseline. Levels of IP-10 (CXCL10), IL-12/23p40, IL-6, sVCAM1, IL-15, sICAM1 and IL-8 (CXCL8) decreased significantly after treatment switch to rituximab. The cytokines IP-10 and IL-12/IL-23p40 displayed the largest difference versus HC at baseline and also the largest relative reduction after therapy switch to rituximab.

    CONCLUSION: We found significant changes in the immunological profile after therapy switch to rituximab in RRMS in the direction towards the values of HC. IP-10 and IL12/IL-23p40 deserve further studies as part of the immunopathogenesis of MS as well as for the mode of action of rituximab in MS.

  • 13.
    Elobeid, Adila
    et al.
    Uppsala, Sweden.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cesarini, Kristina Giuliana
    Uppsala, Sweden.
    Alafuzoff, Irina
    Uppsala, Sweden.
    Correlations Between Mini-Mental State Examination Score, Cerebrospinal Fluid Biomarkers, and Pathology Observed in Brain Biopsies of Patients With Normal-Pressure Hydrocephalus2015In: Journal of Neuropathology and Experimental Neurology, ISSN 0022-3069, E-ISSN 1554-6578, Vol. 74, no 5, p. 470-479Article in journal (Refereed)
    Abstract [en]

    Alzheimer disease (AD)-related pathology was assessed in cortical biopsy samples of 111 patients with idiopathic normal-pressure hydrocephalus. Alzheimer disease hallmark lesions-beta-amyloid (A beta) and hyperphosphorylated tau (HPtau)-were observed in 47% of subjects, a percentage consistent with that for whole-brain assessment reported postmortem in unselected cohorts. Higher-immunostained area fraction of AD pathology corresponded with lower preoperative mini-mental state examination scores. Concomitant A beta and HPtau pathology, reminiscent of that observed in patients with AD, was observed in 22% of study subjects. There was a significant correlation between A beta-immunostained area fraction in tissue and A beta 42 (42-amino-acid form of A beta) in cerebrospinal fluid (CSF). Levels of A beta 42 were significantly lower in CSF in subjects with concomitant A beta and HPtau pathology compared with subjects lacking pathology. Moreover, a significant correlation between HPtau-immunostained area fraction and HPtau in CSF was noted. Both HPtau and total tau were significantly higher in CSF in subjects with concomitant A beta and HPtau pathology compared with subjects lacking pathology. The 42-amino-acid form of A beta (A beta 42) and HPtau in CSF were the most significant predictors of the presence of AD pathology in cortical biopsies. Long-term follow-up studies are warranted to assess whether all patients with idiopathic normal-pressure hydrocephalus with AD pathology progress to AD and to determine the pathologic substrate of idiopathic normal-pressure hydrocephalus.

  • 14. Fahlström, Andreas
    et al.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ericson, Hans
    ABC om: Trigeminus­neuralgi2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 51-52Article in journal (Refereed)
  • 15.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Goldin, Kristina
    Hashemian, Sanaz A.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Lindberg, Agneta
    Persson, Monica
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Neurology, Östersund Hospital, SE-83183 Östersund, Sweden.
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Plasma levels of the endocannabinoid anandamide, related N-acylethanolamines and linoleic acid-derived oxylipins in patients with migraine2017In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 120, p. 15-24Article in journal (Refereed)
    Abstract [en]

    There is evidence that patients with migraine have deficient levels of the endogenous cannabinoid receptor ligand anandamide (AEA). It is not known, however, if this is a localised or generalised phenomenon. In the present study, levels of AEA, related N-acylethanolamines (NAEs) and linoleic acid-derived oxylipins have been measured in the blood of 26 healthy women and 38 women with migraine (26 with aura, 12 without aura) who were matched for age and body-mass index. Blood samples were taken on two occasions: the first sample near the start of the menstrual cycle (when present) and the second approximately fourteen days later. For a subset of migraine patients, two additional blood samples were taken, one during a migraine attack and one approximately 1 month later (to be at the same stage in the menstrual cycle, when present). NAEs and oxylipins were measured by liquid chromatography coupled to mass spectrometry. Twenty-nine lipids were quantified, of which 16 were found to have a high reproducibility of measurement. There were no significant differences in the levels of AEA, the related NAEs stearoylethanolamide and oleoylethanolamide or any of the nine linoleic acid derived oxylipins measured either between migraine patients with vs. without aura, or between controls and migraine patients (after stratification to take into account whether or not the individuals had regular menstruation cycles) in either of the first two samples. Levels of linoleoylethanolamide were lower in the patients with vs. without aura on the second sample but not in the first sample, but the biological importance of this fording is unclear. Due to time-dependent increases in their concentrations ex vivo prior to centrifugation, AEA and oleoylethanolamide levels in the samples collected during migraine attacks were not analysed, but for the other fourteen lipids, there were no significant differences in plasma concentrations during migraine vs. one month later. It is concluded that migraine is not associated with a generalised (as opposed to localised) deficiency in these lipids.

  • 16.
    Irewall, Anna-Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bergström, Lisa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ögren, Joachim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderström, Lars
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Östersund research unit, Umeå University.
    Implementation of telephone-based secondary preventive intervention after stroke and transient ischemic attack - participation rate, reasons for nonparticipation and one-year mortality2014In: Cerebrovascular diseases extra, ISSN 1664-5456, Vol. 4, no 1, p. 28-39Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Patients who experience a stroke or transient ischemic attack (TIA) are known to be at high risk of subsequent vascular events, underscoring the need for secondary preventive intervention. However, previous studies have indicated insufficiency in the implementation of secondary prevention, emphasizing the need to develop effective methods of follow-up. In the present study, we examined the potential of implementing a telephone-based, nurse-led, secondary preventive follow-up in stroke and TIA patients on a population level by analyzing the participation rate, reasons for nonparticipation, and one-year mortality.

    METHODS: Between January 1, 2010 and December 31, 2011, all patients admitted to Östersund hospital, Sweden, and diagnosed with either stroke or TIA were considered for inclusion into the secondary preventive follow-up. Baseline data were collected at the hospital, and reasons for nonparticipation were documented. Multivariate logistic regression was performed to identify predictors of the patient decision not to participate and to explore independent associations between baseline characteristics and exclusion. A one-year follow-up of mortality was also performed; the survival functions of the three groups (included, excluded, declining participation) was calculated using the Kaplan-Meier estimator.

    RESULTS: From a total of 810 identified patients, 430 (53.1%) were included in the secondary preventive follow-up, 289 (35.7%) were excluded mainly due to physical or cognitive disability, and 91 (11.2%) declined participation. Age ≥85 years, ischemic and hemorrhagic stroke, modified Rankin scale score >3, body mass index ≥25, congestive heart failure, and lower education level were independently associated with exclusion, whereas lower education level was the only factor independently associated with the patient decision not to participate. Exclusion was associated with a more than 12 times higher risk of mortality within the first year after discharge.

    CONCLUSION: Population-based implementation of secondary prevention in stroke and TIA patients is limited by the high prevalence of comorbidity and a considerable degree of disability. In our study, a large proportion of patients were unable to participate even in this simple form of secondary preventive follow-up. Exclusion was associated with substantially higher one-year mortality, and education level was independently associated with physical ability as well as the motivation to participate in the secondary preventive follow-up program.

  • 17.
    Irewall, Anna-Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ögren, Joachim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Public Health and Clinical Medicine, Östersund, Sweden.
    Bergström, Lisa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Public Health and Clinical Medicine, Östersund, Sweden.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderström, Lars
    Unit of Research, Development and Education, Region Jämtland Härjedalen, Östersund Hospital, Östersund, Sweden.
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nurse-Led, Telephone-Based, Secondary Preventive Follow-Up after Stroke or Transient Ischemic Attack Improves Blood Pressure and LDL Cholesterol: Results from the First 12 Months of the Randomized, Controlled NAILED Stroke Risk Factor Trial2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, article id e0139997Article in journal (Refereed)
    Abstract [en]

    Background: Enhanced secondary preventive follow-up after stroke or transient ischemic attack (TIA) is necessary for improved adherence to recommendations regarding blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels. We investigated whether nurse-led, telephone-based follow-up was more efficient than usual care at improving BP and LDL-C levels at 12 months after hospital discharge.

    Methods: We randomized 537 patients to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C measurements were performed at 1 month (baseline) and 12 months post-discharge. Intervention group patients who did not meet target values at baseline received additional follow-up, including titration of medication and lifestyle counselling, to reach treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L).

    Results: At 12 months, mean systolic BP, diastolic BP and LDL-C was 3.3 (95% CI 0.3 to 6.3) mmHg, 2.3 mmHg (95% CI 0.5 to 4.2) and 0.3 mmol/L (95% CI 0.1 to 0.4) lower in the intervention group compared to controls. Among participants with values above the treatment goal at baseline, the difference in systolic BP and LDL-C was more pronounced (8.0 mmHg, 95% CI 4.0 to 12.1, and 0.6 mmol/L, 95% CI 0.4 to 0.9). A larger proportion of the intervention group reached the treatment goal for systolic BP (68.5 vs. 56.8%, p = 0.008) and LDL-C (69.7% vs. 50.4%, p < 0.001).

    Conclusions: Nurse-led, telephone-based secondary preventive follow-up, including medication adjustment, was significantly more efficient than usual care at improving BP and LDL-C levels by 12 months post-discharge.

  • 18.
    Irewall, Anna-Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ögren, Joachim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bergström, Lisa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderström, Lars
    Unit of Research, Development and Education, Region Jämtland Härjedalen, Östersund Hospital, Östersund, Sweden.
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nurse-led, telephone-based secondary preventive follow-up benefits stroke/TIA patients with low education: a randomized controlled trial sub-study2019In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 20, article id 52Article in journal (Refereed)
    Abstract [en]

    Background: The objective of this study was to analyze the impact of two forms of secondary preventive followup on the association between education level and levels of blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) after stroke/transient ischemic attack (TIA).

    Methods: We included a population-based cohort of 771 stroke and TIA patients randomly assigned (1:1) to secondary preventive follow-up within primary health care (control) or nurse-led, telephone-based follow-up (intervention) between January 1, 2010, and December 31, 2013, as part of the NAILED (nurse-based ageindependent intervention to limit evolution of disease) stroke risk factor trial. We compared BP and LDL-C levels 12 months after hospital discharge in relation to education level (low, ≤10 years; high, >10 years) separately for the intervention and control groups.

    Results: Among controls, systolic BP (SBP) decreased only among the highly educated (−2.5 mm Hg, 95% confidence interval (CI) −0.2 to −4.8), whereas LDL-C increased in the low-education group (0.2 mmol/L, 95% CI 0.1 to 0.3). At 12 months, controls with low education not more than 70 years of age had higher SBP than controls of the same age with high education (5.8 mm Hg, 95% CI 1.0 to 10.6). In contrast, SBP in the intervention group decreased similarly regardless of education level, LDL-C decreased among those with low education (−0.3 mmol/L, 95% CI −0.2 to −0.4) and, in the subgroup not more than 70 years old, low-educated participants had lower LDL-C at 12 months than those with high education (0.3 mmol/L, 95% CI 0.1 to 0.5).

    Conclusions: Nurse-led, telephone-based secondary preventive follow-up led to comparable improvements in BP across education groups, while routine follow-up disfavored those with low education.

    Trial registration: ISRCTN Registry ISRCTN23868518, June 19, 2012 - Retrospectively registered

  • 19.
    Israelsson, Hanna
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wikkelsö, Carsten
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Kahlon, Babar
    Leijon, Göran
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Vascular risk factors contribute to idiopathic normal pressure hydrocephalus: the INPH-CRasH StudyManuscript (preprint) (Other academic)
    Abstract [en]

    Objective

    The objective was to determine the complete modern vascular risk factor (VRF) profile of idiopathic normal pressure hydrocephalus (INPH) using a large sample of representative INPH-patients and population-based controls, in order to confirm the impact of vascular disease on INPH pathophysiology.

     

    Methods

    All shunted INPH-patients in Sweden 2008-2010 were compared to age- and gender-matched population-based controls. Inclusion criteria: 60-85 years and mini mental state estimation ³23. The ten most important modern VRFs as well as cerebrovascular and peripheral vascular disease were prospectively assessed through blood samples, by-protocol clinical examinations and standardized questionnaires. Investigated VRFs: hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking, diet, alcohol intake, cardiac disease and, physical activity.

     

    Results

    After exclusion, 176 INPH-patients and 368 controls participated. Using multivariable logistic regression, hyperlipidemia (OR: 2.380, 95%CI: 1.434-3.950), diabetes (OR: 2.169, 95%CI: 1.195-3.938), obesity (OR: 5.428, 95%CI: 2.502-11.772) and, psychosocial factors (OR: 5.343, 95%CI: 3.219-8.868) were independently associated with INPH. Hypertension, physical inactivity, cerebrovascular and peripheral vascular disease were overrepresented in INPH, although not independently. The protective factors: moderate alcohol intake and physical activity were overrepresented among the controls. The population attributable risk percentage was 24%.

     

    Conclusions

    Our findings confirm that INPH-patients have a more dangerous VRF-profile and lack the protective factors present in the population. Almost one quarter of INPH could be explained by VRF, suggesting that INPH possibly may be a subgroup of vascular dementia. Targeted interventions against modifiable VRF are likely to have beneficial effects in INPH.

  • 20.
    Israelsson, Hanna
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wikkelsö, Carsten
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Kahlon, Babar
    Leijon, Göran
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vascular risk factors in INPH A prospective case- control study (the INPH-CRasH study)2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, no 6, p. 577-585Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the complete vascular risk factor (VRF) profile of idiopathic normal pressure hydrocephalus (INPH) using a large sample of representative patients with INPH and populationbased controls to determine the extent to which vascular disease influences INPH pathophysiology. Methods: All patients with INPH who underwent shunting in Sweden in 2008-2010 were compared to age-and sex-matched population-based controls. Inclusion criteria were age 60-85 years and no dementia. The 10 most important VRFs and cerebrovascular and peripheral vascular disease were prospectively assessed using blood samples, clinical examinations, and standardized questionnaires. Assessed VRFs were hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking habits, diet, alcohol intake, cardiac disease, and physical activity. Results: In total, 176 patients with INPH and 368 controls participated. Multivariable logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 2.380; 95% confidence interval [CI] 1.434-3.950), diabetes (OR 2.169; 95% CI 1.195-3.938), obesity (OR 5.428; 95% CI 2.502-11.772), and psychosocial factors (OR 5.343; 95% CI 3.219-8.868) were independently associated with INPH. Hypertension, physical inactivity, and cerebrovascular and peripheral vascular disease were also overrepresented in INPH. Moderate alcohol intake and physical activity were overrepresented among the controls. The population-attributable risk percentage was 24%. Conclusions: Our findings confirm that patients with INPH have more VRFs and lack the protective factors present in the general population. Almost 25% of cases of INPH may be explained by VRFs. This suggests that INPH may be a subtype of vascular dementia. Targeted interventions against modifiable VRFs are likely to have beneficial effects on INPH.

  • 21.
    Kockum, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lilja-Lund, Otto
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Larsson, E. -M
    Rosell, M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Söderström, L.
    Virhammar, J.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    The idiopathic normal-pressure hydrocephalus Radscale: a radiological scale for structured evaluation2018In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 3, p. 569-576Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Despite the important role of imaging in diagnosing idiopathic normal‐pressure hydrocephalus (iNPH), a structured overall assessment of radiological signs is still lacking. The purpose of this study was to construct a radiological scale, composed of morphological signs of iNPH, and compare it with clinical symptoms.

    Methods: In this prospective, population‐based study of iNPH, 168 individuals (93 females) [mean age 75 (range 66–92) years] underwent computed tomography of the brain and a neurological examination with assessment of clinical symptoms according to Hellström's iNPH scale. Two radiologists, blinded to clinical data, independently evaluated and measured eight radiological parameters, i.e. Evans’ index, callosal angle, size of temporal horns, narrow high‐convexity sulci, dilated Sylvian fissures, focally dilated sulci, peri‐ventricular hypodensities and bulging of the lateral ventricular roof.

    Results: In a linear regression model, all parameters except ventricular roof bulging were significantly associated with clinical iNPH symptoms. The seven remaining parameters were summarized into a total iNPH Radscale score ranging from 0 to 12. There was a significant correlation (r = 0.55, < 0.001) between the total iNPH Radscale score and clinical symptoms. The inter‐rater agreement for the included radiological parameters was high (intraclass correlation, 0.74–0.97).

    Conclusion: The iNPH Radscale may become a valuable diagnostic screening tool, allowing a structured radiological assessment. A high iNPH Radscale score together with clinical symptoms should raise suspicion of iNPH, motivating further evaluation for shunt surgery.

  • 22. Larsson, Bo
    et al.
    Dahlöf, Carl
    Eeg-Olofson, Orvar
    Fichtel, Åsa
    Laurell, Katarina
    Institutionen för neurovetenskap, Neurologi, Akademiska sjukhuset, Uppsala.
    Återkommande huvudvärk hos barn och tonåringar2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 23, p. 1802-1805Article in journal (Refereed)
    Abstract [sv]

    Återkommande huvudvärk är ett av de vanligaste hälsoproblemen bland skolbarn och rapporteras av cirka en fjärdedel. Den är särskilt vanlig bland flickor i tonåren. Vanligast är huvudvärk av spänningstyp och/eller migrän.

    Hos skolbarn medför återkommande huvudvärk sänkt livskvalitet, högre grad av emotionella och sociala problem samt andra somatiska symtom. Prognosen för sådan huvudvärk är också osäker.

    Det är av stor vikt att lärare och skolsköterskor/läkare tidigt uppmärksammar återkommande huvudvärk hos barn och ungdom så att den blir diagnostiserad och behandlad i enlighet med bästa tillgängliga kunskap. Ett sådant omhändertagande omfattar både aktiv psykologisk och farmakologisk behandling, vilket påtagligt kan minska besvären och deras psykosociala konsekvenser.

  • 23. Laudon Meyer, Eva
    et al.
    Laurell, Katarina
    Department of Neuroscience, Neurology, Uppsala University, Uppsala.
    Artto, Ville
    Bendtsen, Lars
    Linde, Mattias
    Kallela, Mikko
    Tronvik, Erling
    Zwart, John-Anker
    Jensen, Rikke M.
    Hagen, Knut
    Lateralization in cluster headache: a Nordic multicenter study2009In: Journal of Headache and Pain, ISSN 1129-2369, E-ISSN 1129-2377, Vol. 10, no 4, p. 259-263Article in journal (Refereed)
    Abstract [en]

    A slight predominance of cluster pain on the right side has been reported in several studies. The aim of this large retrospective Nordic multicenter study was to estimate the prevalence of right- and left-sided pain in cluster headache (CH) patients with side-locked pain, the prevalence of side shifts in episodic and chronic CH patients, and the occurrence of cranial autonomic symptoms related to pain side. Among 383 cluster patients, 55 (14%) had experienced pain side shift. Of the remaining 328 individuals without side shift, there was no significant difference between the occurrence of right-sided and left-sided pain (54 vs. 46%). The prevalence of side shift was similar for episodic and chronic CH and the occurrence of cranial autonomic symptoms was not influenced by the pain side. In conclusion, previous reports of a side difference in location of cluster pain could not be confirmed in this large Nordic sample.

  • 24.
    Laurell, Katarina
    et al.
    Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden.
    Artto, V
    Bendtsen, L
    Hagen, K
    Kallela, M
    Meyer, E Laudon
    Putaala, J
    Tronvik, E
    Zwart, J-A
    Linde, M
    Migrainous infarction: a Nordic multicenter study2011In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 18, no 10, p. 1220-1226Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Migrainous infarction (MI), i.e., an ischemic stroke developing during an attack of migraine with aura is rare and the knowledge of its clinical characteristics is limited. Previous case series using the International Classification of Headache Disorders (ICHD) included <10 cases which make conclusions less valid. This study aimed to describe characteristics and outcome of MI in a larger sample.

    METHODS: We analyzed demographic data, risk factors, migraine medication, stroke localization, symptoms, and outcome in a sample of 33 patients with MI according to second edition of the ICHD criteria collected from seven Nordic headache clinics.

    RESULTS: Amongst 33 patients with MI, there were 20 (61%) women and 13 (39%) men with the median age for stroke of 39 (range 19-76) years. Traditional risk factors for stroke were rare compared with Scandinavian young ischemic stroke populations. During the acute phase, 12 (36%) patients used ergotamines or triptans. Stroke was located in the posterior circulation in 27 (82%) patients and cerebellum was involved in 7 (21%). Except in two patients with brainstem infarctions, the outcome was favorable with total recovery or limited residual symptoms.

    CONCLUSIONS: The prevalence of traditional risk factors was low and the infarctions were predominantly located in posterior circulation territory, supporting theories of migraine specific mechanisms. The outcome was in general favorable.

  • 25.
    Laurell, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Artto, Ville
    Bendtsen, Lars
    Hagen, Knut
    Häggström, Johan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Linde, Mattias
    Söderström, Lars
    Tronvik, Erling
    Wessman, Maija
    Zwart, John Anker
    Kallela, Mikko
    Premonitory symptoms in migraine: a cross-sectional study in 2714 persons2016In: Cephalalgia, ISSN 0333-1024, E-ISSN 1468-2982, Vol. 36, no 10, p. 951-959Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 26.
    Laurell, Katarina
    et al.
    Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden.
    Larsson, B
    Eeg-Olofsson, O
    Headache in schoolchildren: agreement between different sources of information2003In: Cephalalgia, ISSN 0333-1024, E-ISSN 1468-2982, Vol. 23, no 6, p. 420-428Article in journal (Refereed)
    Abstract [en]

    The level of agreement between different sources of information, i.e. questionnaires, interviews and diaries, was evaluated in a sample of 129 schoolchildren, 69 girls and 60 boys, ranging in age from 7 to 17 years. Headache diagnoses and headache features showed high agreement between questionnaires and subsequent interviews. The concordance between questionnaires and interviews for headache diagnoses increased, and the number of unclassified headaches decreased, when the International Headache Society (IHS) duration criterion was excluded. When comparing headache frequency reported in questionnaires and interviews with diary recordings, the agreement was low and the frequency higher in the diaries. Overall, the agreement between questionnaires, interviews and diaries was not related to age or gender. The questionnaire may serve as a valid source of information in studies of headache in schoolchildren. Prospective recordings in diaries provide additional information, in particular of low-intensity headache. In children, the IHS duration criterion should be modified or excluded.

  • 27.
    Laurell, Katarina
    et al.
    Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden.
    Larsson, B
    Eeg-Olofsson, O
    Prevalence of headache in Swedish schoolchildren, with a focus on tension-type headache2004In: Cephalalgia, ISSN 0333-1024, E-ISSN 1468-2982, Vol. 24, no 5, p. 380-388Article in journal (Refereed)
    Abstract [en]

    To estimate the prevalence of tension-type headache, migraine and other headaches, 1850 schoolchildren, age 7-15 years, from the city of Uppsala, were invited to complete a questionnaire. The response rate was 74.1%. To validate the information from the questionnaires, 131 children and their parents were interviewed. Using the criteria of the International Headache Society, the 1-year prevalence of tension-type headache and migraine was 9.8 and 11.0%, respectively. However, these prevalence rates increased considerably, to 23.0 and 17.0%, respectively, when excluding the criteria defining the number of earlier episodes and duration of headache. The prevalence of headache increased with age, similarly in girls and boys up to 11 years, and thereafter only in girls. The preponderance in teenage girls was even more pronounced for tension-type headache than for migraine. Our results indicate an increase over time in headache prevalence when compared with findings in a study conducted in the same city in 1955.

  • 28.
    Laurell, Katarina
    et al.
    Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden.
    Larsson, Bo
    Eeg-Olofsson, Orvar
    Headache in schoolchildren: association with other pain, family history and psychosocial factors2005In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 119, no 1-3, p. 150-158Article in journal (Refereed)
    Abstract [en]

    Limited information exist about associations between different headache types and other pains, family history of pain, and psychosocial factors among children from the general population suffering from less severe headache. We interviewed 130 schoolchildren together with a parent to find out whether such factors differ between children with mainly infrequent and moderate migraine or tension-type headache as compared to those without primary headache. Children with headache, especially those with migraine reported other pains and physical symptoms more frequently than children without primary headache. Coherently, parents of children suffering from migraine reported their children to have significantly more somatic symptoms than parents of children without primary headache. In addition, first-degree relatives of children with headache suffered from more migraine, other pains, and physical symptoms compared with first-degree relatives of children without primary headache. Children with migraine visited the school nurse, used medication and were absent from school because of headache more often than those with tension-type headache. Few other differences in psychosocial factors were found between the three groups. Migraine among first-degree relatives and the total sum of physical symptoms in children were the strongest predictors of headache in logistic regression analysis. It is concluded that in schoolchildren with mainly infrequent and moderate headache, pain and physical symptoms cluster within individuals as well as their families, however, psychological and social problems are uncommon.

  • 29.
    Laurell, Katarina
    et al.
    Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden.
    Larsson, Bo
    Mattsson, P
    Eeg-Olofsson, O
    A 3-year follow-up of headache diagnoses and symptoms in Swedish schoolchildren2006In: Cephalalgia, ISSN 0333-1024, E-ISSN 1468-2982, Vol. 26, no 7, p. 809-815Article in journal (Refereed)
    Abstract [en]

    Information is sparse concerning the incidence and prognosis of headache in children from the general population, especially of tension-type headache. In this study, headache diagnoses and symptoms were reassessed in 122 out of 130 schoolchildren after 3 years. Nearly 80% of those with headache at first evaluation still reported headache at follow-up. Although the likelihood of experiencing the same headache diagnosis and symptoms was high, about one-fifth of children with tension-type headache developed migraine and vice versa. Female gender predicted migraine and frequent headache episodes predicted overall headache at follow-up. The estimated average annual incidence was 81 and 65 per 1000 children, for tension-type headache and migraine, respectively. We conclude that there is a considerable risk of developing and maintaining headache during childhood. Headache diagnoses should be reassessed regularly and treatment adjusted. Girls and children with frequent headache have a poorer prognosis and therefore intervention is particularly important in these groups.

  • 30.
    Laurell, Katarina
    et al.
    Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden.
    Lundström, Erik
    Migrainous infarction: aspects on risk factors and therapy2012In: Current Pain and Headache Reports, ISSN 1531-3433, E-ISSN 1534-3081, Vol. 16, no 3, p. 255-260Article in journal (Refereed)
    Abstract [en]

    Migraine and stroke are related in more than one way. Migraine with aura is a risk factor for ischemic stroke in women under age 45 years, particularly when combined with other risk factors such as smoking and oral contraceptives. Further, individuals with migraine with aura seem to have more white matter lesions and ischemic infarctions than control patients. Migraine has been correlated to cervical artery dissection, the symptoms of which can mimic migraine. Correspondingly, migraine with aura sometimes is mistaken for stroke. Migrainous infarction is a rare but specific type of ischemic stroke developing during an attack of migraine with aura. It is important to recognize this unusual complication of migraine because the management probably is important. In this review, we will discuss the present knowledge of migrainous infarction, the clinical picture, possible mechanisms, and potential prevention and treatment.

  • 31. Libard, Sylwia
    et al.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Cesarini, Kristina Giuliana
    Alafuzoff, Irina
    Neuronal loss and progression of Alzheimer's disease related pathology observed in a Swedish patient with clinical diagnosis of idiopathic normal pressure hydrocephalus2019In: Brain Pathology, ISSN 1015-6305, E-ISSN 1750-3639, Vol. 29, p. 69-69Article in journal (Other academic)
  • 32.
    Libard, Sylwia
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Cesarini, Kristina Giuliana
    Alafuzoff, Irina
    Progression of Alzheimer's Disease-Related Pathology and Cell Counts in a Patient with Idiopathic Normal Pressure Hydrocephalus2018In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 61, no 4, p. 1451-1462Article in journal (Refereed)
    Abstract [en]

    We had an opportunity to assess the change observed in the brain regarding Alzheimer's disease (AD)-related alterations, cell count, and inflammation that took place during a period of 21 months in a subject with a definite diagnosis of AD and idiopathic Normal Pressure Hydrocephalus (iNPH). Four neuronal markers, i.e., synaptophysin, microtubule associated protein 2, non-phosphorylated neurofilament H (SMI32), and embryonic lethal abnormal visual system proteins 3/4 HuC/HuD (HuC/HuD); three microglial markers CD68, Human Leucocytic Antigen DR, ionized calcium-binding adaptor molecule 1, glial fibrillary acidic protein (GFAP); and AD-related markers, hyperphosphorylated iota (HP iota) and amyloid-beta (A beta, A beta(40), A beta(42)) were assessed. Morphometrically assessed immunoreactivity of all neuronal and all microglial markers and A beta(42) decreased parallel with an increase in the HP iota in the frontal cortex. The expression of GFAP was stable with time. The first sample was obtained during the therapeutic shunting procedure for iNPH, and the second sample was obtained postmortem. Negligible reactive changes were observed surrounding the shunt channel. In conclusion, in the late stage of AD with time, a neuronal loss, increase in the HP iota, and decrease in A beta(42) and microglia was observed, whereas the expression of GFAP was rather stable. The observations described here suggest that when a brain biopsy has been obtained from an adult subject with iNPH, the assessment of postmortem brain is of major significance.

  • 33.
    Molde, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderström, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Parkinsonian symptoms in normal pressure hydrocephalus: a population-based study2017In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 264, no 10, p. 2141-2148Article in journal (Refereed)
    Abstract [en]

    It may be challenging to differentiate normal pressure hydrocephalus (NPH) from neurodegenerative disorders such as Parkinson's disease. In this population-based study, we wanted to describe the frequency of parkinsonian symptoms among individuals with and without NPH, and whether the motor examination part of the Unified Parkinson's Disease Rating Scale (UPDRS-m) score differs between these groups. Furthermore, we wanted to find out whether there was a relationship between UPDRS-m score, NPH symptoms, and radiological signs of NPH. A sample of 168 individuals over the age of 65 with and without self-reported symptoms of NPH underwent a computerized tomography of the brain and clinical examination, including UPDRS-m to grade parkinsonian symptoms. According to diagnostic guidelines, 38 fulfilled criteria for NPH, whereas 130 had unlikely NPH. Bradykinesia was significantly more common among those with NPH (79%) compared to those with unlikely NPH (32%) (p < 0.001). The corresponding figures for rigidity were 43 vs. 15% (p < 0.001), for postural instability 71 vs. 22% (p < 0.001), and for tremor at rest 5 vs. 6% (not significant). The total UPDRS-m score was significantly higher among individuals with NPH (median = 12) than without (median = 1) and correlated significantly with the degree of NPH symptoms (r = -0.72) and ventriculomegaly (r = 0.31). In this study, parkinsonian symptoms, except resting tremor, were frequent in individuals with NPH and correlated with the severity of NPH symptoms. Asymmetric symptoms were uncommon. We recommend a liberal use of neuroradiological imaging when investigating a patient with parkinsonian features.

  • 34. Roos, A.-K.
    et al.
    Wiklund, L.
    Laurell, K.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Discrepancy in prevalence of Huntington's disease in two Swedish regions2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, no 5, p. 511-515Article in journal (Refereed)
    Abstract [en]

    Background: Huntington's disease (HD) is a neurodegenerative disease with an autosomal dominant pattern of inheritance. The prevalence varies between different geographical regions with an estimated average in Europe of about 6/100 000. Parts of northern Sweden are known to have an accumulation of HD, but no prevalence studies have been undertaken for 50 years. Object: The aim of this study was to estimate the prevalence of HD in the two different Swedish counties of Jamtland and Uppsala and compare them with the reported prevalence in Europe. Method: Patients registered with the diagnosis of HD were identified through medical records in each county. Presymptomatic patients were excluded. We also compared the annual number of individuals with HD registered in the database of the National Board of Health and Welfare in these regions, with all of Sweden. Results: The prevalence of HD was found to be 22.1/100 000 in Jamtland and 4.9/100 000 in Uppsala county. The mean age was 62.2 years and 61.8 years, respectively. The annual average of patients with HD registered at inpatient care was 1.5/100 000 in Jamtland, 0.44/100 000 in Uppsala county, and 0.56/100 000 in all of Sweden. Conclusion: The prevalence of patients with the diagnosis of HD is four times higher in the county of Jamtland than in the county of Uppsala, where the prevalence is more similar to the average in Europe. Our results support earlier findings of regional variations of HD prevalence with an accumulation in certain parts of northern Sweden.

  • 35. Shanks, J.
    et al.
    Bloch, K. Markenroth
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Cesarini, K. G.
    Fahlstroem, M.
    Larsson, E-M
    Virhammar, J.
    Aqueductal CSF Stroke Volume Is Increased in Patients with Idiopathic Normal Pressure Hydrocephalus and Decreases after Shunt Surgery2019In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 40, no 3, p. 453-459Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Increased CSF stroke volume through the cerebral aqueduct has been proposed as a possible indicator of positive surgical outcome in patients with idiopathic normal pressure hydrocephalus; however, consensus is lacking. In this prospective study, we aimed to compare CSF flow parameters in patients with idiopathic normal pressure hydrocephalus with those in healthy controls and change after shunt surgery and to investigate whether any parameter could predict surgical outcome.

    MATERIALS AND METHODS: Twenty-one patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched healthy controls were prospectively included and examined clinically and with MR imaging of the brain. Eighteen patients were treated with shunt implantation and were re-examined clinically and with MR imaging the day before the operation and 3 months postoperatively. All MR imaging scans included a phase-contrast sequence.

    RESULTS: The median aqueductal CSF stroke volume was significantly larger in patients compared with healthy controls (103.5 μL; interquartile range, 69.8–142.8 μL) compared with 62.5 μL (interquartile range, 58.3–73.8 μL; P < .01) and was significantly reduced 3 months after shunt surgery from 94.8 μL (interquartile range, 81–241 μL) to 88 μL (interquartile range, 51.8–173.3 μL; P < .05). Net flow in the caudocranial direction (retrograde) was present in 11/21 patients and in 10/21 controls. Peak flow and net flow did not differ between patients and controls. There were no correlations between any CSF flow parameters and surgical outcomes.

    CONCLUSIONS: Aqueductal CSF stroke volume was increased in patients with idiopathic normal pressure hydrocephalus and decreased after shunt surgery, whereas retrograde aqueductal net flow did not seem to be specific for patients with idiopathic normal pressure hydrocephalus. On the basis of the results, the usefulness of CSF flow parameters to predict outcome after shunt surgery seem to be limited.

  • 36.
    Sundström, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lundin, Fredrik
    Kahlon, Babar
    Cesarini, Kristina G
    Leijon, Göran
    Wikkelsö, Carsten
    Incidence and outcome of surgery for adult hydrocephalus patients in Sweden2017In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 31, no 1, p. 21-27Article in journal (Refereed)
    Abstract [en]

    OBJECT: To present population-based and age related incidence of surgery and clinical outcome for adult patients operated for hydrocephalus, registered in the Swedish Hydrocephalus Quality Registry (SHQR).

    METHODS: All patients registered in SHQR during 2004-2011 were included. Data on age, gender, type of hydrocephalus and type of surgery were extracted as well as three months outcome for patients with idiopathic normal pressure hydrocephalus (iNPH).

    RESULTS: The material consisted of 2360 patients, 1229 men and 1131 women, age 63.8 ± 14.4 years (mean ± standard deviation (SD)). The mean total incidence of surgery was 5.1 ± 0.9 surgeries/100,000/year; 4.7 ± 0.9 shunt surgeries and 0.4 ± 0.1 endoscopic third ventriculostomies. For iNPH, secondary communicating hydrocephalus and obstructive hydrocephalus, the incidence of surgery was 2.2 ± 0.8, 1.9 ± 0.3 and 0.8 ± 0.1/100,000/year, respectively. During 2004-2011, the incidence of surgery increased in total (p = .044), especially in age groups 70-79 years and ≥80 years (p = .012 and p = .031). After surgery, 253 of 652 iNPH patients (38.8%) improved at least one step on the modified Rankin scale (mRS). Number needed to treat was 3.0 for improving one patient from unfavourable (mRS 3-5) to favourable (mRS 0-2). The mean score of a modified iNPH scale increased from 54 ± 23 preoperatively to 63 ± 25 postoperatively (p < .0001, n = 704), and 58% improved. No significant regional differences in incidence, surgical techniques or outcome were found.

    CONCLUSIONS: Incidence of hydrocephalus surgery increased significantly during 2004-2011, specifically in elderly patients. Surgical treatment of iNPH markedly improved functional independence, but the improvement rate was low compared to recent single- and multicentre studies. Thus, the potential for surgical improvement is likely lower than generally reported when treating patients as part of everyday clinical care.

  • 37. Tronvik, Erling
    et al.
    Sørensen, Torgeir
    Linde, Mattias
    Bendtsen, Lars
    Artto, Ville
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Pharmacology and Clinical Neuroscience, Östersund Hospital, Östersund.
    Kallela, Mikko
    Zwart, John-Anker
    Hagen, Knut
    The relationship between headache and religious attendance (the Nord-Trøndelag health study- HUNT)2014In: Journal of Headache and Pain, ISSN 1129-2369, E-ISSN 1129-2377, Vol. 15, article id 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Religious belief can be used as a pain coping strategy. Our purpose was to evaluate the relationship between headache and religious activity using prospective data from a large population-based study.

    METHODS: This longitudinal cohort study used data from two consecutive surveys in the Nord-Trøndelag Health Survey (HUNT 2 and 3) performed in 1995-1997; and 2006-2008. Among the 51,383 participants aged ≥ 20 years who answered headache questions at baseline, 41,766 were eligible approximately 11 years later. Of these, 25,177 (60%) completed the question in HUNT 3 regarding religious activity. Frequent religious attendees (fRA) (used as a marker of stronger religious belief than average) were defined as those who had been to church/prayer house at least once monthly during the last six months.

    RESULTS: In the multivariate analyses, adjusting for known potential confounders, individuals with headache 1-14 days/month in HUNT 2 were more likely to be fRA 11 years later than headache-free individuals. Migraine at baseline predisposed more strongly to fRA at follow-up (OR = 1.25; 95% CI 1.19-1.40) than did non-migrainous headache (OR = 1.13; 95% 1.04-1.23). The odds of being fRA was 48% increased (OR 1.48; 95% 1.19-1.83) among those with migraine 7-14 days/month at baseline compared to subjects without headache. In contrast, headache status at baseline did not influence the odds of being frequent visitors of concerts, cinema and/or theatre at follow-up 11 years later.

    CONCLUSIONS: In this prospective study, headache, in particular migraine, at baseline slightly increased the odds of being fRA 11 years later.

  • 38. Virhammar, J
    et al.
    Cesarini, K G
    Laurell, Katarina
    Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden.
    The CSF tap test in normal pressure hydrocephalus: evaluation time, reliability and the influence of pain2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no 2, p. 271-276Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The cerebrospinal fluid tap test (TT) is a diagnostic tool used to select patients with idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. The procedure and the evaluation of the TT vary between centres. We aimed to describe the evaluation time after the TT, to assess the variability between repeated measurements, the interrater agreement of the gait tests chosen and finally to investigate whether pain affects the gait performance post-TT.

    METHODS: Forty patients (21 men and 19 women) under evaluation for iNPH underwent a TT. Standardized gait analyses were performed before and 2, 4, 6, 8 and 24 h after the TT and repeated twice on every occasion. Independent of each other, two investigators evaluated the quality of gait. At each assessment time, the patients graded headache and back pain on a visual analogue scale.

    RESULTS: Twenty-seven patients (15 men and 12 women) responded to TT. Improvements in gait speed and number of steps were significant at every assessment time post-TT. The variability between two measurements was low (Intra class correlation coefficient=0.97), and the inter-rater agreement was good with a κ=0.74. Pain correlated negatively with improvement in gait speed (r=-0.40, P<0.05).

    CONCLUSIONS: We suggest that the TT can be evaluated at any time within the first 24 h and should be repeated if the patient does not initially improve. Gait analysis appears reliable between two evaluators. Further, it is indicated that post-lumbar puncture pain negatively affects the gait and should be minimized.

  • 39. Virhammar, J.
    et al.
    Laurell, K.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ahlgren, A.
    Larsson, E.-M.
    Arterial spin-labeling perfusion MR imaging demonstrates regional CBF decrease in idiopathic normal pressure hydrocephalus2017In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, no 11, p. 2081-2088Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Regional cerebral blood flow has previously been studied in patients with idiopathic normal pressure hydrocephalus with imaging methods that require an intravenous contrast agent or expose the patient to ionizing radiation. The purpose of this study was to assess regional CBF in patients with idiopathic normal pressure hydrocephalus compared with healthy controls using the noninvasive quantitative arterial spin-labeling MR imaging technique. A secondary aim was to compare the correlation between symptom severity and CBF. MATERIALS AND METHODS: Differences in regional cerebral perfusion between patients with idiopathic normal pressure hydrocephalus and healthy controls were investigated with pseudocontinuous arterial spin-labeling perfusion MR imaging. Twenty-one consecutive patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched randomly selected healthy controls from the population registry were prospectively included. The controls did not differ from patients with respect to selected vascular risk factors. Twelve different anatomic ROIs were manually drawn on coregistered FLAIR images. The Holm-Bonferroni correction was applied to statistical analyses. RESULTS: In patients with idiopathic normal pressure hydrocephalus, perfusion was reduced in the periventricular white matter (P < .001), lentiform nucleus (P < .001), and thalamus (P < .001) compared with controls. Cognitive function in patients correlated with CBF in the periventricular white matter (r = 0.60, P < .01), cerebellum (r = 0.63, P < .01), and pons (r = 0.71, P < .001). CONCLUSIONS: Using pseudocontinuous arterial spin-labeling, we could confirm findings of a reduced perfusion in the periventricular white matter, basal ganglia, and thalamus in patients with idiopathic normal pressure hydrocephalus previously observed with other imaging techniques.

  • 40. Virhammar, J.
    et al.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cesarini, K. G.
    Larsson, E. -M
    Preoperative Prognostic Value of MRI Findings in 108 Patients with Idiopathic Normal Pressure Hydrocephalus2014In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 35, no 12, p. 2311-2318Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: MR imaging is used in the diagnostic evaluation of patients with idiopathic normal pressure hydrocephalus. The aim of this study was to describe the prevalence of several imaging features and their prognostic use in the selection of shunt candidates with idiopathic normal pressure hydrocephalus. MATERIALS AND METHODS: Preoperative MR imaging scans of the brain were retrospectively evaluated in 108 patients with idiopathic normal pressure hydrocephalus who had undergone a standardized, clinical evaluation before and 12 months after shunt surgery. The MR imaging features investigated were the Evans index, callosal angle, narrow sulci at the high convexity, dilation of the Sylvian fissure, diameters of the third ventricle and temporal horns, disproportionately enlarged subarachnoid space hydrocephalus, flow void through the aqueduct, focal bulging of the roof of the lateral ventricles, deep white matter hyperintensities, periventricular hyperintensities, and focal widening of sulci and aqueductal stenosis. RESULTS: In logistic regression models, with shunt outcome as a dependent variable, the ORs for the independent variables, callosal angle, disproportionately enlarged subarachnoid space hydrocephalus, and temporal horns, were significant (P < .05), both in univariate analyses and when adjusted for age, sex, and previous stroke. CONCLUSIONS: A small callosal angle, wide temporal horns, and occurrence of disproportionately enlarged subarachnoid space hydrocephalus are common in patients with idiopathic normal pressure hydrocephalus and were significant predictors of a positive shunt outcome. These noninvasive and easily assessed radiologic markers could aid in the selection of candidates for shunt surgery.

  • 41. Virhammar, J
    et al.
    Warntjes, M
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Larsson, E-M
    Quantitative MRI for Rapid and User-Independent Monitoring of Intracranial CSF Volume in Hydrocephalus2016In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 37, no 5, p. 797-801Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Quantitative MR imaging allows segmentation of different tissue types and automatic calculation of intracranial volume, CSF volume, and brain parenchymal fraction. Brain parenchymal fraction is calculated as (intracranial volume - CSF volume) / intracranial volume. The purpose of this study was to evaluate whether the automatic calculation of intracranial CSF volume or brain parenchymal fraction could be used as an objective method to monitor volume changes in the ventricles.

    MATERIALS AND METHODS: A lumbar puncture with drainage of 40 mL of CSF was performed in 23 patients under evaluation for idiopathic normal pressure hydrocephalus. Quantitative MR imaging was performed twice within 1 hour before the lumbar puncture and was repeated 30 minutes, 4 hours, and 24 hours afterward. For each time point, the volume of the lateral ventricles was manually segmented and total intracranial CSF volume and brain parenchymal fraction were automatically calculated by using Synthetic MR postprocessing.

    RESULTS: At 30 minutes after the lumbar puncture, the volume of the lateral ventricles decreased by 5.6 ± 1.9 mL (P < .0001) and the total intracranial CSF volume decreased by 11.3 ± 5.6 mL (P < .001), while brain parenchymal fraction increased by 0.78% ± 0.41% (P < .001). Differences were significant for manual segmentation and brain parenchymal fraction even at 4 hours and 24 hours after the lumbar tap. There was a significant association using a linear mixed model between change in manually segmented ventricular volume and change in brain parenchymal fraction and total CSF volume, (P < .0001).

    CONCLUSIONS: Brain parenchymal fraction is provided rapidly and fully automatically with Synthetic MRI and can be used to monitor ventricular volume changes. The method may be useful for objective clinical monitoring of hydrocephalus.

  • 42.
    Virhammar, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ahlgren, Andre
    Department of Medical Radiation Physics, Lund University.
    Cesarini, Kristina Giuliana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Idiopathic normal pressure hydrocephalus: cerebral perfusion measured with pCASL before and repeatedly after CSF removal2014In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 34, no 11, p. 1771-1778Article in journal (Refereed)
    Abstract [en]

    Pseudo-continuous arterial, spin labeling (pCASL) measurements were performed in 20 patients with idiopathic normal pressure hydrocephalus (iNPH) to investigate whether cerebral blood flow (CBF) increases during the first 24 hours after a cerebrospinal fluid tap test (CSF TT). Five pCASL magnetic resonance imaging (MRI) scans were performed. Two scans were performed before removal of 40 mL CSF, and the other three at 30 minutes, 4 hours, and 24 hours, respectively after the CSF TT. Thirteen different regions of interest (ROIs) were manually drawn on coregistered MR images. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal compared with baseline investigations. The repeatability of CBF measurements at baseline was high, with intraclass correlation coefficients of 0.60 to 0.90 for different ROIs, but the median regional variability was in the range of 5% to 17%. Our results indicate that CBF in white matter close to the lateral ventricles plays a role in the reversibility of symptoms after CSF removal in patients with iNPH.

  • 43. Virhammar, Johan
    et al.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cesarini, Kristina Giuliana
    Larsson, Elna-Marie
    Increase in callosal angle and decrease in ventricular volume after shunt surgery in patients with idiopathic normal pressure hydrocephalus2019In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 130, no 1, p. 130-135Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    Postoperative decrease in ventricle size is usually not detectable either by visual assessment or by measuring the Evans index in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of the present study was to investigate whether the angle between the lateral ventricles (the callosal angle [CA]) increases and ventricular volume decreases after shunt surgery in patients with iNPH.

    METHODS

    Magnetic resonance imaging of the brain was performed before and 3 months after shunt surgery in 18 patients with iNPH. The CA and Evans index were measured on T1-weighted 3D MR images, and ventricular volume contralateral to the shunt valve was measured with quantitative MRI.

    RESULTS

    The CA was larger postoperatively (mean 78°, 95% CI 69°–87°) than preoperatively (mean 67°, 95% CI 60°–73°; p < 0.001). The volume of the lateral ventricle contralateral to the shunt valve decreased from 73 ml (95% CI 66–80 ml) preoperatively to 63 ml (95% CI 54–72 ml) postoperatively (p < 0.001). The Evans index was 0.365 (95% CI 0.35–0.38) preoperatively and 0.358 (95% CI 0.34–0.38) postoperatively (p < 0.05). Postoperative change of CA showed a negative correlation with change of ventricular volume (r = −0.76, p < 0.01).

    CONCLUSIONS

    In this sample of patients with iNPH, the CA increased and ventricular volume decreased after shunt surgery. The relative difference was most pronounced for the CA, indicating that this accessible, noninvasive radiological marker should be evaluated further as an indirect method to determine shunt function in patients with iNPH.

  • 44. Virhammar, Johan
    et al.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Neurology, Department of Neuroscience, Uppsala University.
    Cesarini, Kristina Giuliana
    Larsson, Elna-Marie
    The callosal angle measured on MRI as a predictor of outcome in idiopathic normal-pressure hydrocephalus2014In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 120, no 1, p. 178-184Article in journal (Refereed)
    Abstract [en]

    Object Different neuroimaging biomarkers have been studied to find a tool for prediction of response to CSF shunting in idiopathic normal-pressure hydrocephalus (iNPH). The callosal angle (CA) has been described as useful in discriminating iNPH from ventricular dilation secondary to atrophy. However, the usefulness of the CA as a prognostic tool for the selection of shunt candidates among patients with iNPH is unclear. The aim of this study was to compare the CA in shunt responders with that in nonresponders and clarify whether the CA can serve as a predictor of the outcome. Methods Preoperative MRI brain scans were evaluated in 109 patients who had undergone shunt surgery for iNPH during 2006-2010. Multiplanar reconstruction was performed interactively to obtain a coronal image through the posterior commissure, perpendicular to the anterior-posterior commissure plane. The CA was measured as the angle between the lateral ventricles on the coronal image. The patients were examined clinically before surgery and at 12 months postoperatively. Results Shunt responders had a significantly smaller mean preoperative CA compared with nonresponders: 59° (95% CI 56°-63°) versus 68° (95% CI 61°-75°) (p < 0.05). A CA cutoff value of 63° showed the best prognostic accuracy. Conclusions The preoperative CA is smaller in patients whose condition improves after shunt surgery and may be a useful tool in the selection of shunt candidates among patients with iNPH.

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