Change search
Refine search result
1 - 22 of 22
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Birnefeld, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    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.
    Cerebral arterial pulsatility is associated with features of small vessel disease in patients with acute stroke and TIA: a 4D flow MRI study2020In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 267, no 3, p. 721-730Article in journal (Refereed)
    Abstract [en]

    Cerebral small vessel disease (SVD) is a major cause of stroke and cognitive impairment. However, the underlying mechanisms behind SVD are still poorly understood. High cerebral arterial pulsatility has been suggested as a possible cause of SVD. In population studies, arterial pulsatility has been linked to white matter hyperintensities (WMH), cerebral atrophy, and cognitive impairment, all features of SVD. In stroke, pulsatility data are scarce and contradictory. The aim of this study was to investigate the relationship between arterial pulsatility and SVD in stroke patients. With a cross-sectional design, 89 patients with acute ischemic stroke or TIA were examined with MRI. A neuropsychological assessment was performed 1 year later. Using 4D flow MRI, pulsatile indices (PI) were calculated for the internal carotid artery (ICA) and middle cerebral artery (M1, M3). Flow volume pulsatility (FVP), a measure corresponding to the cyclic expansion of the arterial tree, was calculated for the same locations. These parameters were assessed for associations with WMH volume, brain volume and cognitive function. ICA-FVP was associated with WMH volume (β = 1.67, 95% CI: [0.1, 3.24], p = 0.037). M1-PI and M1-FVP were associated with decreasing cognitive function (β = - 4.4, 95% CI: [- 7.7, - 1.1], p = 0.009 and β = - 13.15, 95% CI: [- 24.26, - 2.04], p = 0.02 respectively). In summary, this supports an association between arterial pulsatility and SVD in stroke patients, and provides a potential target for further research and preventative treatment. FVP may become a useful biomarker for assessing pulsatile stress with PCMRI and 4D flow MRI.

  • 2.
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Environmental risk factors for the occurrence of multiple sclerosis2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background. Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system that typically debuts around age 30. About 2.3 million people are affected in the world today, and besides trauma it is the most common cause of neurological disability among young adults in the western world. The disease likely develops via a complex interplay of genetic vulnerability and environmental risk factors, and adolescence is assumed to be a critical time for disease initiation. The aim of this study was to investigate how MS risk in different age groups is influenced by vitamin D, infections with Epstein-Barr virus and Human herpesviruses 6A and B as well as the metabolic markers leptin and insulin.

    Methods. In this nested case-control study we identified pre-symptomatically drawn blood samples from individuals below age 40, that later developed relapsing remitting MS. This was done through crosslinking of the Swedish MS registry, or a local database, with six Swedish biobanks containing remainders of samples used in microbiological analyses. For each case, one control matched for biobank, sex, date of sampling and age of sampling was selected. These samples were then analysed to determine antibody reactivity against Epstein-Barr virus and Human herpesvirus 6A and B, as well as measure concentrations of leptin, insulin and 25-hydroxyvitamin D. The effect of these variables on MS risk was estimated using conditional logistic regression, both in the entire case-control material as well as stratified into three groups by age at sampling (<20, 20-29 and 30-39) and by sex.

    Results. Human herpesvirus 6A, but not B, was consistently associated with an increased risk of developing MS. In contrast, Epstein-Barr virus demonstrated an age dependent pattern indicating that early infection may be protective against MS while later infection increases the risk. As for the metabolic markers, insulin was not associated with MS while elevated levels of leptin showed an association with increased MS risk both among individuals below 20 years of age and among all men. For women there was instead an inverse association in the oldest group, aged 30-39, when adjusting the leptin analysis for insulin concentrations. Finally, having vitamin D concentrations in the top quintile was associated with decreased MS risk, without evidence of a stronger effect in young subjects.

    Conclusion. These results implicate Human herpesvirus 6A and leptin as risk factors for MS development. They also further support a protective role for vitamin D in MS etiology and provide serological evidence of an age dependency of Epstein-Barr virus infection as it relates to MS risk.

  • 3.
    Biström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Andersen, Oluf
    Alonso-Magdalena, Lucia
    Jons, Daniel
    Gunnarsson, Martin
    Vrethem, Magnus
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Leptin levels are associated with multiple sclerosis risk2020In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, article id 1352458520905033Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obesity early in life has been linked to increased risk of developing multiple sclerosis (MS). Leptin and insulin are both associated with obesity, making them suitable candidates for investigating this connection.

    OBJECTIVE: To determine if leptin and insulin are risk factors for relapsing-remitting multiple sclerosis (RRMS).

    METHODS: In this nested case-control study using blood samples from Swedish biobanks, we compared concentrations of leptin and insulin in 649 individuals who later developed RRMS with 649 controls matched for biobank, sex, age and date of sampling. Only pre-symptomatically drawn samples from individuals below the age of 40 years were included. Conditional logistic regression was performed on z-scored values to calculate odds ratios (ORs) with 95% confidence intervals (CIs).

    RESULTS: A 1-unit leptin z-score increase was associated with increased risk of MS in individuals younger than 20 years (OR = 1.4, 95% CI = 1.1-1.9) and in all men (OR = 1.4, 95% CI = 1.0-2.0). In contrast, for women aged 30-39 years, there was a lower risk of MS with increased leptin levels (OR = 0.74, 95% CI = 0.54-1.0) when adjusting for insulin levels.

    CONCLUSION: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals.

  • 4.
    Biström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Jons, Daniel
    Engdahl, Elin
    Gustafsson, Rasmus
    Huang, Jesse
    Brenner, Nicole
    Butt, Julia
    Alonso-Magdalena, Lucia
    Gunnarsson, Martin
    Vrethem, Magnus
    Bender, Noemi
    Waterboer, Tim
    Granåsen, Gabriel
    Olsson, Tomas
    Kockum, Ingrid
    Andersen, Oluf
    Fogdell-Hahn, Anna
    Sundström, Peter
    Epstein-Barr virus infection after adolescence and Human herpesvirus 6A as risk factors for multiple sclerosisManuscript (preprint) (Other academic)
  • 5. Engdahl, Elin
    et al.
    Gustafsson, Rasmus
    Huang, Jesse
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Lima Bomfim, Izaura
    Stridh, Pernilla
    Khademi, Mohsen
    Brenner, Nicole
    Butt, Julia
    Michel, Angelika
    Jons, Daniel
    Hortlund, Maria
    Alonso-Magdalena, Lucia
    Hedström, Anna Karin
    Flamand, Louis
    Ihira, Masaru
    Yoshikawa, Tetsushi
    Andersen, Oluf
    Hillert, Jan
    Alfredsson, Lars
    Waterboer, Tim
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Olsson, Tomas
    Kockum, Ingrid
    Fogdell-Hahn, Anna
    Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis2019In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 2715Article in journal (Refereed)
    Abstract [en]

    Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10-22), and increased risk of future MS (OR = 2.22, p = 2 × 10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1*13:01-DQA1*01:03-DQB1*06:03 haplotype while the main association for IE1B was DRB1*13:02-DQA1*01:02-DQB1*06:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.

  • 6.
    Israelsson Larsen, Hanna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Cerebrospinal Fluid Shunting Improves Long-Term Quality of Life in Idiopathic Normal Pressure Hydrocephalus2019In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, article id nyz297Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The short- and long-term impact of cerebrospinal fluid shunting on quality of life (QoL) in idiopathic normal pressure hydrocephalus (INPH) is poorly understood.

    OBJECTIVE: To investigate QoL in shunted INPH patients compared to the population and to investigate which factors influence QoL in INPH.

    METHODS: INPH patients consecutively shunted in Sweden during 2008-2010 were scrutinized. Population-based controls were age- and sex-matched to the patients. Included participants were the following: 176 INPH patients and 368 controls. QoL was assessed using the EuroQol 5-dimension 5-level (EQ5D5L) instrument, which measures overall QoL and health status in 5 dimensions. Independency (accommodation and/or need for in-home care) and comorbidities were assessed. Patients were followed up 6-45 mo after surgery (mean follow-up time: 21 mo).

    RESULTS: Shunting improved QoL (P < .001) and health status in all dimensions (P < .005). Shunted INPH patients had lower QoL than controls (P < .001). The patients' health status in mobility, self-care, daily activities, and anxiety/depression was worse than the controls both before and after surgery (P < .001). The main predictors of low QoL in INPH were symptoms of depression (P < .001) and severity of gait disturbance (P = .001). Fewer INPH patients than controls lived independently (45% vs 85%, P < .001). Time after shunting had no influence on QoL.

    CONCLUSION: QoL remains improved in shunted INPH patients at a mean follow-up time of 21 mo, but the patients do not reach the same QoL as the population. Symptoms of depression and severity of gait disturbance are the strongest predictors of low QoL in INPH.

  • 7. Karlsson, Britt M.
    et al.
    Koch, Mona
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Nimodipine affects the microcirculation and modulates the vascular effects of acetylcholinesterase inhibition2003In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 108, no 2, p. 141-149Article in journal (Refereed)
    Abstract [en]

    The present investigation was undertaken in order to study whether microvascular effects of the calcium antagonist nimodipine induces changes that can explain an increased detoxification of the highly toxic cholinesterase inhibitor soman. Anaesthetised, tracheotomised and artificially ventilated rats were treated intra-peritoneally (ip) with nimodipine, 10 mg kg(-1) or vehicle followed one hour later by the exposure to 45 microg kg(-1) soman (iv). Nimodipine per se induced a vasodilation in the intestine, myocardium and other muscles. In the abdominal skin soman elicited a significant vasoconstriction that was turned into an increased blood flow after nimodipine pre-treatment. A slight vasoconstriction in diaphragm of soman intoxicated rats was turned into a significant vasodilation by nimodipine pre-treatment. In the intestinal parts no effect of soman was detected. However, in nimodipine pretreated animals soman induced a significant vasoconstriction. The capacity of soman detoxifying processes, i.e. enzymatic hydrolysis and covalent binding to different esterases, is unequally distributed throughout the body. Together with the knowledge of the detoxifying processes of cholinesterase inhibition the results support our theory, that nimodipine alters the peripheral blood flow in a beneficial way resulting in improved detoxification ability.

  • 8.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Vasodilation: Vascular smooth muscle, Peptides, Autonomic Nerves and Endothelium: Thyrotropin-releasing hormone and cerebral blood flow.1988Book (Refereed)
  • 9.
    Koskinen, Lars-Owe D.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sperber, Göran O.
    Regional glucose metabolism in the rabbit brain in control and TRH-treated animals1986In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 126, no 3, p. 349-353Article in journal (Refereed)
    Abstract [en]

    The local cerebral metabolism in urethane anaesthetized control and TRH-treated rabbits was studied with the [14C]2-deoxyglucose method. In the controls, the glucose use was found to be highest in regions known to have a high blood flow and low in regions with low flow. The glucose consumption was, calculated using the constants found by Kennedy et al. in monkeys, 23.5 +/- 6.0 mumol 100 g-1 min-1 in parietal cortex. The TRH was infused at a dose of 0.06 mg kg-1 min-1 which is known to cause vasodilation in the brain. No marked influence of the peptide on the glucose use was detected. It was concluded that the previously reported cerebral vasodilation caused by TRH is not due to an increase in cerebral metabolism.

  • 10. Lehtipalo, S
    et al.
    Winsö, O
    Koskinen, L O
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Johansson, G
    Biber, B
    Cutaneous sympathetic vasoconstrictor reflexes for the evaluation of interscalene brachial plexus block.2000In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 44, no 8, p. 946-52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although signs of sympathetic blockade following interscalene brachial plexus block include Horner's syndrome, increased skin temperature and vasodilatation, the degree of sympathetic blockade is not easily determined. The aim of this study was, therefore, to use activation of cutaneous finger pad vasoconstrictor reflexes for description and quantification of the degree of sympathetic blockade following unilateral interscalene brachial plexus block.

    METHODS: Eight patients scheduled for acromioplasty under general anesthesia were studied. An interscalene plexus catheter was inserted preoperatively on the side to be operated upon and used postoperatively for administration of bupivacaine, given as a bolus (1.25 mg kg(-1)) followed by a continuous infusion (0.25 mg kg(-1) h(-1)). Skin blood flow (SBF) in the pad of the index finger was assessed by the laser Doppler technique, and regional skin vascular resistance (RVR) was calculated. The inspiratory gasp test (apnea at end-inspiration) or a local heat provocation were used as provocations of the cutaneous microcirculation.

    RESULTS: Interscalene brachial plexus block increased SBF and decreased RVR at rest, and produced satisfactory sensory and motor block. The inspiratory gasp test decreased SBF and increased RVR in the unblocked arm, while the opposite, increased SBF and decreased RVR, were observed during local heat provocation. In the blocked arm, these gasp-induced cutaneous vasoconstrictor and heat-induced vasodilator responses were attenuated.

    CONCLUSIONS: Interscalene brachial plexus block reduces regional sympathetic nervous activity, illustrated by increases in skin blood flow, skin temperature and attenuated vasoconstrictor responses to an inspiratory gasp. The inspiratory gasp vasoconstrictive response is a powerful and sensitive indicator for monitoring the sympathetic blockade following interscalene brachial plexus block.

  • 11.
    Linden, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Svenningsson, Anders
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Inflammatory activity and vitamin D levels in an MS population treated with rituximab2019In: Multiple Sclerosis Journal, Experimental, Translational and Clinical, E-ISSN 2055-2173, Vol. 5, no 1, article id 2055217319826598Article in journal (Refereed)
    Abstract [en]

    Background: Most multiple sclerosis patients on disease-modifying treatment at Umeå University Hospital are treated with rituximab and the prevalence of vitamin D supplementation has increased over time. Follow-up studies of these off-label treatments are needed.

    Objective: To study inflammatory activity and adverse effects in rituximab-treated multiple sclerosis patients, and associations with 25-hydroxy-vitamin D levels.

    Methods: Retrospectively collected data on repeated estimates of relapses, disability, side effects, magnetic resonance imaging, laboratory measures including 25-hydroxy-vitamin D levels and self-perceived health.

    Results: In 272 multiple sclerosis patients with a mean follow-up of 43 months, we identified seven possible relapses during active rituximab treatment. On magnetic resonance imaging examination, new T2 lesions were seen in 1.3% (10 out of 792 scans), and 0.25% (two out of 785 scans) showed contrast enhancement. Adjusted 25-hydroxy-vitamin D levels in samples drawn close to all magnetic resonance images with new T2 lesions were lower compared to the remainder (62 vs. 81 nmol/l; P = 0.030). Levels of 25-hydroxy-vitamin D were associated with self-perceived health (r = 0.18, P = 0.041, n = 130) and C-reactive protein (r = -0.13, P = 0.042) but not with the risk of side effects.

    Conclusion: The inflammatory activity in this rituximab-treated multiple sclerosis population that increasingly used vitamin D supplementation was extremely low. Higher 25-hydroxy-vitamin D levels were associated with beneficial outcomes.

  • 12.
    Lindvall, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Intracranial Hypertension due to Cerebral Venous Sinus Thrombosis following Head Trauma: A Report of Two Cases.2013In: Case Reports in Neurology, ISSN 1662-680X, E-ISSN 1662-680X, Vol. 5, no 3, p. 168-174Article in journal (Refereed)
    Abstract [en]

    Cerebral venous sinus thrombosis (CVST) may occur following head trauma and contribute to intracranial hypertension that mandates immediate action. Anticoagulant therapy is the first line of treatment in CVST but may not be applicable in patients with head trauma. Here, we report on the treatment of 2 patients with CVST. In 1 patient, there was an attempt to perform thrombectomy and thrombolysis, and eventually a decompressive craniectomy was performed. In this patient, there was an excellent outcome. In the other patient, an immediate decompressive craniectomy was performed that did not improve the outcome.

  • 13. Luna, Gustavo
    et al.
    Alping, Peter
    Burman, Joachim
    Fink, Katharina
    Fogdell-Hahn, Anna
    Gunnarsson, Martin
    Hillert, Jan
    Langer-Gould, Annette
    Lycke, Jan
    Nilsson, Petra
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Svenningsson, Anders
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Vrethem, Magnus
    Olsson, Tomas
    Piehl, Fredrik
    Frisell, Thomas
    Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies2020In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 177, no 2, p. 184-191Article in journal (Refereed)
    Abstract [en]

    Importance: Although highly effective disease-modifying therapies for multiple sclerosis (MS) have been associated with an increased risk of infections vs injectable therapies interferon beta and glatiramer acetate (GA), the magnitude of potential risk increase is not well established in real-world populations. Even less is known about infection risk associated with rituximab, which is extensively used off-label to treat MS in Sweden.

    Objective: To examine the risk of serious infections associated with disease-modifying treatments for MS.

    Design, Setting, and Participants: This nationwide register-based cohort study was conducted in Sweden from January 1, 2011, to December 31, 2017. National registers with prospective data collection from the public health care system were used. All Swedish patients with relapsing-remitting MS whose data were recorded in the Swedish MS register as initiating treatment with rituximab, natalizumab, fingolimod, or interferon beta and GA and an age-matched and sex-matched general population comparator cohort were included.

    Exposures: Treatment with rituximab, natalizumab, fingolimod, and interferon beta and GA.

    Main Outcomes and Measures: Serious infections were defined as all infections resulting in hospitalization. Additional outcomes included outpatient treatment with antibiotic or herpes antiviral medications. Adjusted hazard ratios (HRs) were estimated in Cox regressions.

    Results: A total of 6421 patients (3260 taking rituximab, 1588 taking natalizumab, 1535 taking fingolimod, and 2217 taking interferon beta/GA) were included, plus a comparator cohort of 42 645 individuals. Among 6421 patients with 8600 treatment episodes, the mean (SD) age at treatment start ranged from 35.0 (10.1) years to 40.4 (10.6) years; 6186 patients were female. The crude rate of infections was higher in patients with MS taking interferon beta and GA than the general population (incidence rate, 8.9 [95% CI, 6.4-12.1] vs 5.2 [95% CI, 4.8-5.5] per 1000 person-years), and higher still in patients taking fingolimod (incidence rate, 14.3 [95% CI, 10.8-18.5] per 1000 person-years), natalizumab (incidence rate, 11.4 [95% CI, 8.3-15.3] per 1000 person-years), and rituximab (incidence rate, 19.7 [95% CI, 16.4-23.5] per 1000 person-years). After confounder adjustment, the rate remained significantly higher for rituximab (HR, 1.70 [95% CI, 1.11-2.61]) but not fingolimod (HR, 1.30 [95% CI, 0.84-2.03]) or natalizumab (HR, 1.12 [95% CI, 0.71-1.77]) compared with interferon beta and GA. In contrast, use of herpes antiviral drugs during rituximab treatment was similar to that of interferon beta and GA and lower than that of natalizumab (HR, 1.82 [1.34-2.46]) and fingolimod (HR, 1.71 [95% CI, 1.27-2.32]).

    Conclusions and Relevance: Patients with MS are at a generally increased risk of infections, and this differs by treatment. The rate of infections was lowest with interferon beta and GA; among newer treatments, off-label use of rituximab was associated with the highest rate of serious infections. The different risk profiles should inform the risk-benefit assessments of these treatments.

  • 14. Magnusson, B M
    et al.
    Koskinen, L D
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    In vitro percutaneous penetration of topically applied capsaicin in relation to in vivo sensation responses.2000In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 195, no 1-2, p. 55-62Article in journal (Refereed)
    Abstract [en]

    Capsaicin, the primary pungent element in several spices, elicits a variety of physiological effects which are due to neurogenic responses. The aim of the study was to explore the in vivo sensation responses of capsaicin and to compare the results with the in vitro percutaneous absorption of the substance. The overall objectives were to determining an in vitro-in vivo correlation for capsaicin. Capsaicin was applied in a chamber on the volar forearm of twelve volunteers and in a flow-through diffusion chamber on excised human epidermal membranes. Topical administration of capsaicin produced a complex cutaneous sensation that changed in intensity and quality as a function of time and was characterized by sting, prick, burn and pain. Percutaneous steady-state penetrations of capsaicin with a receptor fluid consisting either of 4% bovine serum albumin in phosphate buffered saline or 50% ethanol in water were 28.2+/-2.7 and 29.6+/-2.9 microg/cm(2) per h, respectively. The corresponding cumulative penetrated amounts of capsaicin after 30 min were 14. 7+/-1.7 and 19.2+/-2.1 microg/cm(2), respectively. The present investigation indicates that there is a good correlation between in vivo physiological responses and in vitro percutaneous penetration of topically applied capsaicin.

  • 15. Magnusson, B M
    et al.
    Koskinen, L O
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Koch, M
    Karlsson, K
    Biological effects after percutaneous absorption of thyrotropin-releasing hormone and its analogue M-TRH.2001In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 22, no 1, p. 73-9Article in journal (Refereed)
    Abstract [en]

    Besides its well known endocrinological effects, thyrotropin-releasing hormone (TRH) has potential clinical value in the treatment of neurotrauma and various neurologic and psychiatric disorders. The aim of this study was to assess if transdermal delivery of TRH and its analogue, M-TRH, in the presence of enhancers, is an effective means for administration of the peptides. Using the in vitro diffusion cell method, the effect of ethanol and a terpene on the transdermal penetration of the peptides across full-thickness rat skin were studied. Steady-state permeability values for TRH and M-TRH were 8.7 +/- 2.2 and 6.7 +/- 1.4 microg/cm(2) h, respectively. The addition of 3 % terpene in combination with 47 % ethanol increased the penetration of TRH and M-TRH to 16.2 +/- 1.7 and 14.6 +/- 2.1 microg/cm(2) h, respectively. Rats were studied in vivo for release of thyroid-stimulating hormone (TSH) as a biologic effect after transdermally delivered peptide. Topical application of TRH and M-TRH induced an increase in TSH serum concentration from 0.32 +/- 0.09 ng/ml to 32.6 +/- 5.0 and 22.9 +/- 7.6 ng/ml, respectively, after 30 min. The addition of terpene and ethanol in combination with TRH or M-TRH, increased the TSH release to 43.0 +/- 3.8 and 48.4 +/- 4.0 ng/ml, respectively. It is concluded that, in the rat, peptides can be absorbed through the skin with retained biologic activity, and in amounts sufficient to elicit a physiological response.

  • 16. Neuwirth, Christoph
    et al.
    Braun, Nathalie
    Claeys, Kristl G
    Bucelli, Robert
    Fournier, Christina
    Bromberg, Mark
    Petri, Susanne
    Goedee, Stephan
    Lenglet, Timothée
    Leppanen, Ron
    Canosa, Antonio
    Goodman, Ira
    Al-Lozi, Muhammad
    Ohkubo, Takuya
    Hübers, Annemarie
    Atassi, Nazem
    Abrahao, Agessandro
    Funke, Andreas
    Appelfeller, Martin
    Tümmler, Anke
    Finegan, Eoin
    Glass, Jonathan D
    Babu, Suma
    Ladha, Shafeeq S
    Kwast-Rabben, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Juntas-Morales, Raul
    Coffey, Amina
    Chaudhry, Vinay
    Vu, Tuan
    Saephanh, Chow
    Newhard, Colleen
    Zakrzewski, Marion
    Rosier, Esther
    Hamel, Nancy
    Raheja, Divisha
    Raaijman, Jesper
    Ferguson, Toby
    Weber, Markus
    Implementing Motor Unit Number Index (MUNIX) in a large clinical trial: Real world experience from 27 centres2018In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 129, no 8, p. 1756-1762Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Motor Unit Number Index (MUNIX) is a quantitative neurophysiological method that reflects loss of motor neurons in Amyotrophic Lateral Sclerosis (ALS) in longitudinal studies. It has been utilized in one natural history ALS study and one drug trial (Biogen USA) after training and qualification of raters.

    METHODS: Prior to testing patients, evaluators had to submit test-retest data of 4 healthy volunteers. Twenty-seven centres with 36 raters measured MUNIX in 4 sets of 6 different muscles twice. Coefficient of variation of all measurements had to be <20% to pass the qualification process. MUNIX COV of the first attempt, number of repeated measurements and muscle specific COV were evaluated.

    RESULTS: COV varied considerably between raters. Mean COV of all raters at the first measurements was 12.9% ± 13.5 (median 8.7%). Need of repetitions ranged from 0 to 43 (mean 10.7 ± 9.1, median 8). Biceps and first dorsal interosseus muscles showed highest repetition rates. MUNIX variability correlated considerably with variability of compound muscle action potential.

    CONCLUSION: MUNIX revealed generally good reliability, but was rater dependent and ongoing support for raters was needed.

    SIGNIFICANCE: MUNIX can be implemented in large clinical trials as an outcome measure after training and a qualification process.

  • 17. Ryska, Pavel
    et al.
    Slezak, Ondrej
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Zizka, Jan
    Radiological markers of idiopathic normal pressure hydrocephalus: Relative comparison of their diagnostic performance2020In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 408, article id 116581Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Numerous radiological measures have been proposed as imaging biomarkers of idiopathic normal pressure hydrocephalus (iNPH), however, the number of studies systematically comparing their diagnostic values remains limited. The study objective was to compare the diagnostic performance of fifteen cross-sectional imaging iNPH biomarkers.

    MATERIALS AND METHODS: Eighty subjects were prospectively enrolled in the study: 35 subjects with clinically confirmed iNPH and 45 matched healthy controls (HC). Values of linear, angular and index measurements including three newly proposed biomarkers were obtained from 3T brain MRI studies by two independent readers. Diagnostic performance of biomarkers was studied by using receiver operating characteristic (ROC) analysis and t-statistic.

    RESULTS: All biomarkers studied were able to reliably differentiate iNPH subjects from HC (p < .001) except for cella media-to-temporal horn ratio. Z-Evans index, vertical cella media and vertical frontal horn diameters showed the highest discriminatory power between iNPH and HC groups (area under curve >0.99). Simple linear measurements of vertical (0.99) or horizontal (0.95) frontal horn diameters showed results comparable to calculated ratios, i.e. z-Evans (0.99) and Evans (0.96) indexes, respectively.

    CONCLUSION: The best diagnostic performance among fifteen radiological iNPH biomarkers was found in linear measurements referring to caudocranial alterations of the ventricular geometry, outweighing those referring to laterolateral ventricular enlargement (as e.g. commonly used Evans index). Simple linear measurements of vertical or horizontal frontal horn diameters showed comparable results to calculated, more time-consuming z-Evans or Evans indexes, respectively.

  • 18.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Department of Clinical Sciences, Danderyd Hospital AB, Karolinska Institutet Danderyd Hospital, Stockholm,Sweden.
    Prevention of post-dural puncture headache: a randomized controlled trial2020In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331Article in journal (Refereed)
    Abstract [en]

    Background and purpose: We investigated 952 subjects undergoing diagnostic lumbar puncture (LP) to study the effects of needle size, needle design and stylet reinsertion on the risk of post‐dural puncture headache (PDPH).

    Methods: This randomized double‐blind study was performed at Umeå University Hospital in Sweden during 2013–2018. Subjects were randomly assigned one of three needles [22 gauge (G) atraumatic, 25G atraumatic and 25G cutting] and stylet reinsertion before needle withdrawal or not. The main outcome measure was PDPH assessed by standardized telephone interview(s) 5 days after the LP, repeated until headache cessation. We used logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CI) for PDPH.

    Results: The mean (SD) age was 51.1 (16.7) years and 53.6% were females. The smaller bore (25G) atraumatic needle incurred a lower risk of headache compared with the larger bore (22G) atraumatic needle [22.0% (69/314) vs. 30.2% (98/324); OR, 0.65; 95% CI, 0.45–0.93] and compared with the cutting needle [32.8% (103/314); OR, 0.58; 95% CI, 0.40–0.82]. Reinserting the stylet before needle withdrawal did not reduce the risk of headache.

    Conclusions: These data suggest that a 25G atraumatic needle is superior to a larger atraumatic needle, and to a same‐sized cutting needle, in preventing PDPH after diagnostic LP. In contrast to one earlier report, this study did not find that stylet reinsertion was effective in preventing PDPH. This study provides class I evidence that a small atraumatic needle decreases the risk of PDPH and that stylet reinsertion does not influence PDPH risk.

  • 19.
    Sandström, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy. Umeå University.
    Schalling, Ellika
    Karolinska Institutet, Klinisk vetenskap, Intervention och teknik, Logopedi.
    Karlsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Hartelius, Lena
    Göteborgs universitet, Neurovetenskap och fysiologi, Sektionen för hälsa och rehabilitering.
    Speech following DBS for essential tremor: Effects of chronic and high-amplitude stimulation in the posterior subthalamic area2020Conference paper (Other academic)
    Abstract [en]

    Deep brain stimulation (DBS) can be very effective in alleviating tremor, but adverse effects on speech are frequently reported, especially following bilateral DBS. Most of the existing literature on DBS and speech deals with the effects of DBS targeting the subthalamic nucleus or the ventral intermediate nucleus of the thalamus, which are the traditional targets for Parkinson’s disease and essential tremor, respectively. More recently, the posterior subthalamic area (PSA) has been highlighted as a particularly effective target for tremor; however, there are limited studies of PSA-DBS effects on speech.

    We report speech outcomes for 14 persons with essential tremor during chronic PSA-DBS and at unilateral high-amplitude PSA-stimulation.

    The objectives were to answer the following questions:

    • To what extent is speech function, and in particular articulation and voice, affected by chronic PSA-DBS?
    • How is speech affected by unilateral high-amplitude stimulation
    • Is bilateral chronic PSA-DBS worse for speech than unilateral PSA-stimulation?
  • 20.
    Sjöberg, Rickard L
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Department of Neurosurgery, University Hospital of Northern Sweden, 901 85 Umeå, Sweden.
    Wu, Wendy Yi-Ying
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Dahlin, Anna M.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tsavachidis, Spiridon
    Bondy, Melissa L.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males: a case control study2019In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 145, no 2, p. 287-294Article in journal (Refereed)
    Abstract [en]

    Background: The Mono-amine oxidase-A (MAO-A) enzyme is involved in the degradation and regulation of catecholamines such as serotonin, dopamine, epinephrine and nor-epinephrine. Preclinical studies suggest that this enzyme may contribute to an environment favorable for growth of malignant glioma. The MAO-A gene is located on the X-chromosome and has at least one functional genetic polymorphism. The aim of the present study was to explore possible effects of MAO-A genotype on development of glioblastoma in males.

    Methods: Genotypes for 437 glioma cases and 876 population-based controls from the Swedish Glioma International Case–Control study (GICC) were compared. We analyzed the germline DNA using the Illumina Oncoarray. We selected seven single nucleotide polymorphisms (SNPs) located in the MAO-A gene, and imputed genotypes based on data from the 1000 genomes project. We used 1579 male glioblastoma cases and 1875 controls comprising the whole GICC cohort for subsequent validation of findings.

    Results: The rs144551722 SNP was a significant predictor of development of glioblastoma in males (p-value = 0.0056) but not in females even after correction for multiple testing. We conducted haplotype analysis to confirm an association between MAO-A gene and risk of glioblastoma (p-value = 0.016). We found similar results in the validation sample.

    Conclusions: These results suggest the possibility of a role for the MAO-A enzyme and the MAO-A gene in the development of glioblastoma in males.

  • 21.
    Steensland, Ingrid
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Treatment of Restless legs with a pump: efficacy and complications2020In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Restless legs (RLS) has a prevalence of 2.5-15 % in the general population.. For those who suffer from a medically refractory RLS, intrathecal morphine treatment has been shown to be effective. The aim of this retrospective study was to investigate efficacy, complications and side effects in patients treated over several years with an implantable pump. A comparison was done to a group of patients treated with a similar pump system due to spasticity.

    MATERIALS AND METHODS: The charts of ten patients with severe or very severe RLS have been reviewed. These patients have received an intrathecal drug delivery system during 2000 -2016. To compare the rate of complications, a control group of 20 patients treated with intrathecal baclofen due to spasticity was included in the study. Their time of treatment corresponded to the RLS patients'.

    RESULTS: The severity of symptoms related to RLS decreased significantly after treatment. Doses required ranged from 68 to 140 µg/day. Two cases of side effects were detected; one case with nausea and dizziness and one case with headache and fatigue. The rate of mechanical-, infectious- and other complications were similar between the two groups.

    CONCLUSIONS: In light of the decrease in symptom severity and the low rate of side effects, intrathecal morphine can be considered an adequate treatment for those suffering from medically refractory RLS. The occurrence of complications did not differ between subjects with RLS and spasticity.

  • 22. Zeiler, Frederick A.
    et al.
    Ercole, Ari
    Beqiri, Erta
    Cabeleira, Manuel
    Thelin, Eric P.
    Stocchetti, Nino
    Steyerberg, Ewout W.
    Maas, Andrew I. R.
    Menon, David K.
    Czosnyka, Marek
    Smielewski, Peter
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Association between Cerebrovascular Reactivity Monitoring and Mortality Is Preserved When Adjusting for Baseline Admission Characteristics in Adult Traumatic Brain Injury: A CENTER-TBI Study2019In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042Article in journal (Refereed)
    Abstract [en]

    Cerebral autoregulation, as measured using the pressure reactivity index (PRx), has been related to global patient outcome in adult patients with traumatic brain injury (TBI). To date, this has been documented without accounting for standard baseline admission characteristics and intracranial pressure (ICP). We evaluated this association, adjusting for baseline admission characteristics and ICP, in a multi-center, prospective cohort. We derived PRx as the correlation between ICP and mean arterial pressure in prospectively collected multi-center data from the High-Resolution Intensive Care Unit (ICU) cohort of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Multi-variable logistic regression models were analyzed to assess the association between global outcome (measured as either mortality or dichotomized Glasgow Outcome Score-Extended [GOSE]) and a range of covariates (IMPACT [International Mission for Prognosis and Analysis of Clinical Trials] Core and computed tomography [CT] variables, ICP, and PRx). Performance of these models in outcome association was compared using area under the receiver operating curve (AUC) and Nagelkerke's pseudo-R2. One hundred ninety-three patients had a complete data set for analysis. The addition of percent time above threshold for PRx improved AUC and displayed statistically significant increases in Nagelkerke's pseudo-R2 over the IMPACT Core and IMPACT Core + CT models for mortality. The addition of PRx monitoring to IMPACT Core ± CT + ICP models accounted for additional variance in mortality, when compared to models with IMPACT Core ± CT + ICP alone. The addition of cerebrovascular reactivity monitoring, through PRx, provides a statistically significant increase in association with mortality at 6 months. Our data suggest that cerebrovascular reactivity monitoring may provide complementary information regarding outcomes in TBI.

1 - 22 of 22
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf