uu.seUppsala University Publications
Change search
Refine search result
1 - 34 of 34
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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. Bone, L.
    et al.
    Dahl, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Lensch, M.
    Chance, P.
    Kelly, T.
    Le Guern, E.
    Magi, S.
    Parry, G.
    Shapiro, H.
    Wang, S.
    Fischbeck, K.
    New connexin32 muations associated with X-linked Charcot-Marie-Tooth disease1995In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 45, no 10, p. 1863-6Article in journal (Refereed)
    Abstract [en]

    Analysis of the connexin32 gene in patients with X-linked Charcot-Marie-Tooth disease shows mutations distributed throughout the molecule, with all domains affected except the fourth transmembrane domain and the distal carboxy terminus. Sequence analysis of DNA from 19 unrelated patients detected six novel mutations and three previously reported mutations. Identification of additional mutations extends the distribution of connexin32 mutations in X-linked Charcot-Marie-Tooth disease and shows that specific mutations recur in additional families.

  • 2.
    Burman, Joachim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Fox, Robert J.
    Cleveland Clin, Neurol Inst, Mellen Ctr Multiple Sclerosis, Cleveland, OH 44106 USA..
    Autologous hematopoietic stem cell transplantation for MS: Safer than previously thought2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, no 22, p. 2072-2073Article in journal (Other academic)
  • 3.
    Burman, Joachim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zelano, Johan
    University of Gothenburg, Sahlgrenska Academy, Department of Clinical Neuroscience, Gothenburg.; Sahlgrenska University Hospital, Gothenburg.
    Epilepsy in multiple sclerosis: A nationwide population-based register study.2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, no 24, p. 2462-2468Article in journal (Refereed)
    Abstract [en]

    Objective: To determine the cumulative incidence of epilepsy in a population-based cohort of patients with multiple sclerosis (MS) and to investigate the association between epilepsy and clinical features of MS.

    Methods: All available patients in the Swedish MS register (n = 14,545) and 3 age- and sex-matched controls per patient randomly selected from the population register (n = 43,635) were included. Data on clinical features of MS were retrieved from the Swedish MS register, and data on epilepsy and death were retrieved from comprehensive patient registers.

    Results: The cumulative incidence of epilepsy was 3.5% (95% confidence interval [CI] 3.17–3.76) in patients with MS and 1.4% (95% CI 1.30–1.52) in controls (risk ratio 2.5, 95% CI 2.19–2.76). In a Cox proportional model, MS increased the risk of epilepsy (hazard ratio 3.2, 95% CI 2.64–3.94). Patients with relapsing-remitting MS had a cumulative incidence of epilepsy of 2.2% (95% CI 1.88–2.50), whereas patients with progressive disease had a cumulative incidence of 5.5% (95% CI 4.89–6.09). The cumulative incidence rose continuously with increasing disease duration to 5.9% (95% CI 4.90–7.20) in patients with disease duration ≥34 years. Patients with an Expanded Disability Status Scale (EDSS) score ≥7 had a cumulative incidence of epilepsy of 5.3% (95% CI 3.95–7.00). Disease duration and EDSS score were associated with epilepsy after multiple logistic regression (odds ratio [OR] 1.03, 95% CI 1.01–1.04 per year, p = 0.001; and OR 1.2, 95% CI 1.09–1.26 per EDSS step, p < 0.0001).

    Conclusions: Epilepsy is more common among patients with MS than in the general population, and a diagnosis of MS increases the risk of epilepsy. Our data suggest a direct link between severity of MS and epilepsy.

  • 4.
    Canto Moreira, Nuno
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ribeiro, Valentina
    Hospital S. Antonio, Porto, Portugal.
    Teixeira, João
    Hospital S. Antonio, Porto, Portugal.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Visualisation of the fetal lip and palate: is brain-targeted MRI reliable?2011In: Neurology, ISSN 0028-3878, E-ISSN 1526-632XArticle in journal (Other academic)
    Abstract [en]

    Introduction: The purpose of the study was to evaluate the ability of brain-targeted MRI to assess the anatomy of the fetal upper lip and palate.

     

    Methods: Two independent readers made a blind retrospective review of 60 MRI of fetuses of 20 to 38 gestational weeks (GW). Fifty-five fetuses had normal post-natal follow-up.  Five fetuses had oro-facial anomalies at post-natal follow-up, including five cleft lips (two bilateral, three unilateral), four cleft primary palates (two bilateral, two unilateral) and two cleft secondary palates.

    The upper lip, primary palate, secondary palate and nasal septum were scored into four levels, from evidently normal to evidently abnormal. In case of a suspected pathology, the readers attempted a diagnosis.

     

    Results: Interobserver agreement (weighted kappa) was 0.79 for the upper lip, 0.70 for the primary palate, 0.86 for the secondary palate, and 0.90 for the nasal septum. The scoring levels of the readers did not change significantly across gestational age.

    The readers identified 100% of all pathological cases. The normality was correctly scored in 96-100% of the normal lips and primary palates and in 93-97% of the normal secondary palates depending on the reader. A deviated septum was only scored in two fetuses with unilateral cleft palates.

     

    Conclusion:  MRI in experienced hands seems reliable for assessment of the fetal lip and palate, even in brain-targeted examinations. Attention should therefore be paid to the lip and palate in all fetal MRI examinations, since unsuspected clefts may be revealed.

     

     

  • 5. Caroli, Anna
    et al.
    Prestia, Annapaola
    Galluzzi, Samantha
    Ferrari, Clarissa
    van der Flier, Wiesje M.
    Ossenkoppele, Rik
    Van Berckel, Bart
    Barkhof, Frederik
    Teunissen, Charlotte
    Wall, Anders E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Carter, Stephen F.
    Schoell, Michael
    Choo, Il Han
    Grimmer, Timo
    Redolfi, Alberto
    Nordberg, Agneta
    Scheltens, Philip
    Drzezga, Alexander
    Frisoni, Giovanni B.
    Mild cognitive impairment with suspected nonamyloid pathology (SNAP) Prediction of progression2015In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 84, no 5, p. 508-515Article in journal (Refereed)
    Abstract [en]

    Objectives:The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI).Methods:We measured markers of amyloid pathology (CSF -amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [F-18]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A+/A- and N+/N- based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A-N+ cases.Results:The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A-N-, A+N-, SNAP, and A+N+, respectively; the proportion of APOE epsilon 4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N- and A+N+ groups (p 0.005). Hypometabolism in SNAP patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A-N-, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N- patients did not (hazard ratio = 1.13, p = 0.771). In A+N- and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r = 0.42, p = 0.073).Conclusions:Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile.

  • 6. Chaturvedi, S.
    et al.
    Zivin, J.
    Breazna, A.
    Amarenco, P.
    Callahan, A.
    Goldstein, L. B.
    Hennerici, M.
    Sillesen, H.
    Rudolph, A.
    Welch, M. A.
    Terent, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Effect of atorvastatin in elderly patients with a recent stroke or transient ischemic attack2009In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 72, no 8, p. 688-94Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It is unclear whether patients age 65 years and over with a recent stroke or TIA benefit from statin treatment to a similar degree as younger patients. METHODS: The 4,731 patient cohort in the SPARCL study was divided into an elderly group (65 and over) and a younger group. The primary endpoint (fatal or nonfatal stroke) and secondary endpoints were analyzed, with calculation of the hazard ratio (HR) and p values from a Cox regression model. RESULTS: There were 2,249 patients in the elderly group and 2,482 in the younger group. The baseline LDL (133 mg/dL) and total cholesterol were comparable in the two groups. The elderly and younger groups had a 61.4 mg/dL and 58.7 mg/dL decrease in mean LDL during the trial. The primary endpoint was reduced by 26% in younger patients (HR 0.74, 0.57-0.96, p = 0.02) and by 10% in elderly subjects (HR 0.90, 0.73-1.11, p = 0.33). A test of heterogeneity for a treatment-age interaction was not significant (p = 0.52). The risk of stroke or TIA (HR 0.79, p = 0.01), major coronary events (HR 0.68, p = 0.035), any coronary heart disease event (HR 0.61, p = 0.0006), and revascularization procedures (HR 0.55, p = 0.0005) was reduced in the elderly group. CONCLUSIONS: There was no heterogeneity in the stroke reduction seen with atorvastatin in the elderly and younger groups. Cardiac events and revascularization procedures were also lower in both the elderly and younger subgroups treated with atorvastatin. These results support the use of atorvastatin in elderly patients with recent stroke or TIA.

  • 7.
    Edelvik, Anna
    et al.
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Flink, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Malmgren, Kristina
    Univ Gothenburg, Dept Clin Neurosci & Rehabil, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Prospective and longitudinal long-term employment outcomes after resective epilepsy surgery2015In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 85, no 17, p. 1482-1490Article in journal (Refereed)
    Abstract [en]

    Objective:To investigate long-term employment outcomes after resective epilepsy surgery in a national population-based cohort of adults.Methods:In the Swedish National Epilepsy Surgery Register, all adults who were operated with resective epilepsy surgery from 1995 to 2010 were identified. Two-year follow-up was available for 473/496, 5-year follow-up for 220/240, 10-year follow-up for 240/278, and 15-year follow-up for 85/109 patients.Results:There were no significant changes in employment outcome over time at group level, but for those with full-time employment at baseline, 79%, 79%, 57%, and 47% of seizure-free patients were in full-time work at 2-, 5-, 10-, and 15-year follow-up, compared to patients with benefits at baseline, where 16%, 27%, 31%, and 33% of seizure-free patients worked full time at these time points (p = 0.018 at 10 years). More patients with full-time work had ability to drive, a family of their own, and higher educational status than patients in part-time work or on benefits. Univariate predictors for employment at long term were having employment preoperatively, higher education, favorable seizure outcome, male sex, and younger age at surgery. Multivariate predictors were having employment preoperatively, favorable seizure outcome, and younger age.Conclusions:The best vocational outcomes occurred in seizure-free patients who were employed or students at baseline, which may reflect a higher general psychosocial level of function. Younger age also predicted better employment outcomes and it therefore seems plausible that early referral for surgery could contribute to better vocational outcomes.

  • 8. Edelvik, Anna
    et al.
    Rydenhag, Bertil
    Olsson, Ingrid
    Flink, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kallen, Kristina
    Malmgren, Kristina
    Long-term outcomes of epilepsy surgery in Sweden A national prospective and longitudinal study2013In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 81, no 14, p. 1244-1251Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate prospective, population-based long-term outcomes concerning seizures and antiepileptic drug (AED) treatment after resective epilepsy surgery in Sweden. Methods: Ten-and 5-year follow-ups were performed in 2005 to 2007 for 278/327 patients after resective epilepsy surgery from 1995 to 1997 and 2000 to 2002, respectively. All patients had been prospectively followed in the Swedish National Epilepsy Surgery Register. Ninety-three patients, who were presurgically evaluated but not operated, served as controls. Results: In the long term (mean 7.6 years), 62% of operated adults and 50% of operated children were seizure-free, compared to 14% of nonoperated adults (p < 0.001) and 38% of nonoperated children (not significant). Forty-one percent of operated adults and 44% of operated children had sustained seizure freedom since surgery, compared to none of the controls (p < 0.0005). Multivariate analysis identified >= 30 seizures/month at baseline and long epilepsy duration as negative predictors and positive MRI to be a positive predictor of long-term seizure-free outcome. Ten years after surgery, 86% of seizure-free children and 43% of seizure-free adults had stopped AEDs in the surgery groups compared to none of the controls (p < 0.0005). Conclusions: This population-based, prospective study shows good long-term seizure outcomes after resective epilepsy surgery. The majority of the patients who are seizure-free after 5 and 10 years have sustained seizure freedom since surgery. Many patients who gain seizure freedom can successfully discontinue AEDs, more often children than adults. Classification of evidence: This study provides Class III evidence that more patients are seizure-free and have stopped AED treatment in the long term after resective epilepsy surgery than nonoperated epilepsy patients.

  • 9.
    Ekbom, Karl-Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Restless legs syndrome1960In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 10, no 9, p. 868-873Article in journal (Refereed)
  • 10. Fertleman, C. R.
    et al.
    Ferrie, C. D.
    Aicardi, J.
    Bednarek, N. A. F.
    Eeg-Olofsson, Orvar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Elmslie, F. V.
    Griesemer, D. A.
    Goutières, F.
    Kirkpatrick, M.
    Malmros, I. N. O.
    Pollitzer, M.
    Rossiter, M.
    Roulet-Perez, E.
    Schubert, R.
    Smith, V. V.
    Testard, H.
    Wong, V.
    Stephenson, J. B. P.
    Paroxysmal extreme pain disorder (previously familial rectal pain syndrome)2007In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 69, no 6, p. 586-595Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To describe the clinical phenotype of paroxysmal extreme pain disorder (previously called familial rectal pain syndrome), an autosomal dominant condition recently shown to be a sodium channelopathy involving SCN9A. METHODS: An international consortium of clinicians, scientists, and affected families was formed. Clinical details of all accessible families worldwide were collected, including age at onset, features of attacks, problems between attacks, investigational results, treatments tried, and evolution over time. A validated pain questionnaire was completed by 14 affected individuals. RESULTS: Seventy-seven individuals from 15 families were identified. The onset of the disorder is in the neonatal period or infancy and persists throughout life. Autonomic manifestations predominate initially, with skin flushing in all and harlequin color change and tonic attacks in most. Dramatic syncopes with bradycardia and sometimes asystole are common. Later, the disorder is characterized by attacks of excruciating deep burning pain often in the rectal, ocular, or jaw areas, but also diffuse. Attacks are triggered by factors such as defecation, cold wind, eating, and emotion. Carbamazepine is effective in almost all who try it, but the response is often incomplete. CONCLUSIONS: Paroxysmal extreme pain disorder is a highly distinctive sodium channelopathy with incompletely carbamazepine-sensitive bouts of pain and sympathetic nervous system dysfunction. It is most likely to be misdiagnosed as epilepsy and, particularly in infancy, as hyperekplexia and reflex anoxic seizures.

  • 11. Gonzalez-Perez, Antonio
    et al.
    Gaist, David
    Wallander, Mari-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    McFeat, Gillian
    Garcia-Rodriguez, Luis A.
    Mortality after hemorrhagic stroke Data from general practice (The Health Improvement Network)2013In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 81, no 6, p. 559-565Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate short-term case fatality and long-term mortality after intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) using data from The Health Improvement Network database. Methods: Thirty-day case fatality was stratified by age, sex, and calendar year after ICH and SAH using logistic regression. Cox proportional hazards regression analyses were used to estimate the risk of death during the first year of follow-up and survivors at 1 year. Results: Case fatality after ICH was 42.0%, compared with 28.7% after SAH. It increased with age (ICH: 29.7% for 20-49 years, 54.6% for 80-89 years; SAH: 20.3% for 20-49 years, 56.7% for 80-89 years; both p-trend < 0.001), and decreased over the period 2000-2001 to 2006-2008 (ICH: from 53.1% to 35.8%, p-trend < 0.001; SAH: from 33.3% to 24.7%, p-trend = 0.02). Risk of death was significantly higher among stroke patients during the first year of follow-up compared with controls (ICH: hazard ratio [HR] 2.60, 95% confidence interval [CI] 2.09-3.24, p < 0.01; SAH: HR 2.87,95% CI 2.07-3.97, p < 0.01) and remained elevated among survivors at 1 year (ICH: HR 2.02, 95% CI 1.75-2.32, p < 0.01; SAH: HR 1.32, 95% CI 1.02-1.69, p = 0.03). Conclusions: More than one-third of individuals die in the first month after hemorrhagic stroke, and patients younger than 50 years are more likely to die after ICH than SAH. Short-term case fatality has decreased over time. Patients who survive hemorrhagic stroke have a continuing elevated risk of death compared with matched individuals from the general population.

  • 12. Kilarski, Laura L.
    et al.
    Achterberg, Sefanja
    Devan, William J.
    Traylor, Matthew
    Malik, Rainer
    Lindgren, Arne
    Pare, Guillame
    Sharma, Pankaj
    Slowik, Agniesczka
    Thijs, Vincent
    Walters, Matthew
    Worrall, Bradford B.
    Sale, Michele M.
    Algra, Ale
    Kappelle, L. Jaap
    Wijmenga, Cisca
    Norrving, Bo
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Goris, An
    Franke, Andre
    Sudlow, Cathie
    Rothwell, Peter M.
    Levi, Christopher
    Holliday, Elizabeth G.
    Fornage, Myriam
    Psaty, Bruce
    Gretarsdottir, Solveig
    Thorsteinsdottir, Unnar
    Seshadri, Sudha
    Mitchell, Braxton D.
    Kittner, Steven
    Clarke, Robert
    Hopewell, Jemma C.
    Bis, Joshua C.
    Boncoraglio, Giorgio B.
    Meschia, James
    Ikram, M. Arfan
    Hansen, Bjorn M.
    Montaner, Joan
    Thorleifsson, Gudmar
    Stefanson, Kari
    Rosand, Jonathan
    de Bakker, Paul I. W.
    Farrall, Martin
    Dichgans, Martin
    Markus, Hugh S.
    Bevan, Steve
    Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.122014In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 83, no 8, p. 678-685Article in journal (Refereed)
    Abstract [en]

    Objectives: To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases. Methods: Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls. Results: In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p = 7.12 x 10(-11)) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p = 0.695). Conclusion: Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage.

  • 13.
    Kimber, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tajsharghi, H.
    Kroksmark, A-K
    Oldfors, A.
    Tulinius, M.
    A mutation in the fast skeletal muscle troponin I gene causes myopathy and distal arthrogryposis2006In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 67, no 4, p. 597-601Article in journal (Refereed)
    Abstract [en]

    Objective: To describe a three-generation family with distal arthrogryposis associated with myopathy and caused by a mutation in the gene encoding for sarcomeric thin filament protein troponin I, TNNI2. Methods: The authors performed clinical investigations and reviewed medical records. Muscle biopsy specimens were obtained for morphologic analysis. Genomic DNA was extracted from blood and analyzed for mutations in TNNI2. Results: The five affected individuals had predominantly distal congenital joint contractures, mild facial involvement (mild micrognathia, narrow palpebral fissures), and no detectable muscle weakness. The four affected adults had slightly increased levels of creatine kinase in blood, and muscle biopsy specimens showed findings of myopathy with changes restricted to type 2 fibers. These included variability of muscle fiber size, internalized nuclei, and increased interstitial connective tissue. Analysis of TNNI2 encoding the troponin I isoform expressed in type 2 muscle fibers disclosed a heterozygous three-base in-frame deletion, 2,918-2,920del, skipping the highly conserved lysine at position 176. The mutation was present in all 5 affected individuals but was not identified in any of the 11 unaffected family members. Conclusion: Distal arthrogryposis type 1 is genetically heterogeneous, and myopathy due to sarcomeric protein dysfunction may be one underlying cause of the disease.

  • 14. Kors, E. E.
    et al.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Vanmolkot, K. R.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Haan, Jan
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Flink, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Ginjaar, H.B.
    Frants, R.R.
    Ferrari, M.D.
    van den Maagdenberg, A. M.
    Childhood, epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new CACNA1A mutation2004In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 63, no 6, p. 1136-1137Article in journal (Refereed)
  • 15.
    Lee, Duk-Hee
    et al.
    Kyungpook Natl Univ, Sch Med, Dept Prevent Med, Daegu, South Korea.
    Porta, Miquel
    Univ Autonoma Barcelona, Sch Med, Hosp del Mar, Inst Med Res IMIM, Barcelona, Spain.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Jacobs, David R
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Neurotoxic chemicals in adipose tissue: A role in puzzling findings on obesity and dementia2018In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, no 4, p. 176-182Article in journal (Refereed)
    Abstract [en]

    Midlife obesity is associated with increased risk of dementia, whereas late-life obesity is commonly associated with a lower risk of dementia. Although methodologic issues are often discussed in this apparent risk reversal, chronic exposure to low-dose organochlorine pesticides (OCPs), an emerging risk factor for dementia in general populations, may contribute to a direct explanation for these differences. OCPs are strong lipophilic chemicals with very long half-lives (several years), primarily stored in adipose tissue and very slowly released and metabolized over years. As serum concentrations of neurotoxic OCPs strongly correlate with brain OCPs (r = 0.95), any condition enhancing the release of OCPs from the adipose tissue into circulation would increase the risk of dementia. Increased release of OCPs from adipose tissue typically occurs in (1) dysfunctional adipocytes accompanied by uncontrolled lipolysis and (2) weight loss. Weight gain may help sequester circulating OCPs in adipose tissue. As obesity is the most common reason that adipocytes become dysfunctional, midlife obesity can increase dementia risk through the chronic release of OCPs into circulation. However, late-life obesity potentially decreases dementia risk because weight loss after midlife will increase the release of OCPs while weight gain may actually decrease the release. These countervailing forces may underlie paradoxical associations with dementia of obesity in midlife vs late life which is influenced by weight change after midlife. This hypothesis should be tested in future experimental and human studies on obesity and dementia.

  • 16. LeWitt, Peter
    et al.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    New developments in levodopa therapy2004In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 62, no Suppl. 1, p. s9-S16Article in journal (Refereed)
    Abstract [en]

    More than 30 years after its development, levodopa is still the most effective treatment for the symptomatic control of Parkinson's disease (PD). Although a number of therapies have been developed in an attempt to improve PD management, such as dopaminergic agonists and inhibitors of COMT and MAO-B, most patients still depend on levodopa alone because of its superior ability to control PD symptoms. The issue of toxicity has been raised by in vitro studies suggesting that levodopa might be toxic to dopaminergic neurons, but this has since been answered by in vivo studies finding no evidence of toxicity and possibly even neurotrophic-like effects. A more pressing concern regarding levodopa is its association with the development of motor complications after long-term use. Pulsatile dopaminergic stimulation as a result of erratic absorption and the short half-life of levodopa have been central issues in attempts to explain this occurrence. Evidence suggests that altering the delivery of levodopa to provide a more continuous supply of this drug to the brain may result in improved control of PD symptoms.

  • 17. Linnankivi, T
    et al.
    Valanne, L
    Paetau, A
    Alafuzoff, Irina
    Kuopio University, Finland.
    Hakumäki, J M
    Kivelä, T
    Lönnqvist, T
    Mäkitie, O
    Pääkkönen, L
    Vainionpää, L
    Vanninen, R
    Herva, R
    Pihko, H
    Cerebroretinal microangiopathy with calcifications and cysts.2006In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 67, no 8, p. 1437-43Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Extensive cerebral calcifications and leukoencephalopathy have been reported in two rare disorders Coats plus and leukoencephalopathy with calcifications and cysts. In the latter, a progressive formation of parenchymal brain cysts is a special feature, whereas Coats plus is characterized by intrauterine growth retardation, bilateral retinal telangiectasias and exudations (Coats disease), sparse hair, and dysplastic nails without cyst formation.

    METHODS: We identified 13 patients, including two pairs of siblings, with extensive cerebral calcifications and leukoencephalopathy. We reviewed clinical, ophthalmologic, radiologic and neuropathologic data of seven deceased patients and studied five patients prospectively.

    RESULTS: Eleven patients were small for gestational age; the other symptoms emerged from infancy to adolescence. All patients had neurologic symptoms including seizures, spasticity, dystonia, ataxia, and cognitive decline. Progressive intracerebral calcifications involved deep gray nuclei, brainstem, cerebral and cerebellar white matter, and dentate nuclei and were accompanied by diffuse white matter signal changes and, in five patients, cerebral cysts. Eleven patients had retinal telangiectasias or angiomas. Additional features were skeletal and hematologic abnormalities, intestinal bleeding, and poor growth. Neuropathologic examination showed extensive calcinosis and abnormal small vessels with thickened, hyalinized wall and reduced lumen.

    CONCLUSIONS: Our data suggest that Coats plus syndrome and leukoencephalopathy with calcifications and cysts belong to the same spectrum. The primary abnormality seems to be an obliterative cerebral angiopathy involving small vessels, leading to dystrophic calcifications via slow necrosis and finally to formation of cysts and secondary white matter abnormalities.

  • 18.
    Mattsson, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Tomson, T
    Eriksson, Ö
    Brännström, L
    Ringbäck Weitoft, G
    Sociodemographic differences in antiepileptic drug prescriptions to adult epilepsy patients2010In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 74, no 4, p. 295-301Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: According to the Swedish Health Care Act, patients should be provided with the health care they need, regardless of sociodemographic status. We investigated whether in Sweden sociodemographic differences are associated with access to expert health care and antiepileptic drug (AED) prescriptions in epilepsy. METHOD: Patients with epilepsy were identified in the National Patient Register. Persons >or=18 years on continuous AED treatment in 2006 were identified in the recently established Swedish Prescribed Drug Register. Data on sociodemographic variables were obtained from several other national registers. We linked data to examine whether epilepsy patients' access to neurologists and the prescription of individual AEDs are related to sex, age, educational level, area of residence, region of birth, or income. We also assessed whether AEDs are prescribed differently to patients with epilepsy by neurologists as compared to non-neurologists. RESULTS: We identified 26,124 epilepsy patients in the register who were on continuous AED treatment (effective sample). Being women, young, highly educated, having high incomes, and residing in a larger city meant being more often treated by a neurologist than by other specialists. The prescriptions of AEDs differed according to gender, age, education, place of residence, and income. Lamotrigine and levetiracetam were prescribed to a larger extent by a neurologist rather than by other specialists. CONCLUSIONS: This nationwide cross-sectional study of epilepsy patients indicates that sociodemographic characteristics are important for access to neurologists and prescriptions of individual antiepileptic drugs. Prospective studies using patient-related outcomes are needed to analyze the consequences of these differences.

  • 19.
    Melberg, Atle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Dahl, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Hetta, Jerker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Valind, S.
    Nennesmo, I.
    Lundberg, Per Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Neuroimaging study in autosomal dominant cerebellar ataxia, deafness, and narcolepsy1999In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 53, no 9, p. 2190-2Article in journal (Refereed)
    Abstract [en]

    Four patients affected with autosomal dominant cerebellar ataxia, deafness, and narcolepsy underwent brain CT and MRI. Radiologic findings were supratentorial atrophy (more pronounced than infratentorial atrophy), pronounced dilatation of the third ventricle, low T2 signal intensity in the basal ganglia, loss of cerebral cortex-white matter differentiation, and periventricular high-signal rims. 2-[18F]Fluoro-2-deoxy-D-glucose PET was done with one patient, without specific findings. Genetic analyses excluded SCA-1, SCA-2, SCA-3, SCA-6, SCA-7, DRPLA, and huntingtin gene mutations.

  • 20. Moeller, Sina
    et al.
    Lau, Nga M.
    Green, Peter H. R.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Higgins, Joseph J.
    Rajadhyaksha, Anjali M.
    Alaedini, Armin
    Lack of association between autism and anti-GM1 ganglioside antibody2013In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 81, no 18, p. 1640-1641Article in journal (Other academic)
    Abstract [en]

    Forty of 54 children with autism were reported to have an elevated antibody response to GM1 ganglioside that correlated with disease severity.1 Antiganglioside autoantibodies, especially those directed at GM1, are known to be associated with and play a pathogenic role in some immune-mediated peripheral neuropathies.2,3 The presumed link between autism and anti-GM1 antibodies, therefore, implies that testing may identify a sizable subset of patients who would benefit from immunomodulatory therapy. To evaluate the proposed association between autism and anti-GM1 antibodies, serum samples from children diagnosed with autism by strict clinical criteria and those without autism were analyzed using a standard, validated immunoassay protocol.

  • 21.
    Neubauer, Bernd A.
    et al.
    Dept of Pediatric Neurology, University of Giessen-Marburg, Giessen, Germany.
    Waldegger, S.
    Heinzinger, J.
    Hahn, A.
    Kurlemann, G.
    Fiedler, B.
    Eberhard, F.
    Muhle, H.
    Stephani, U.
    Garkisch, S.
    Eeg-Olofsson, Orvar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Müller, U.
    Sander, T.
    KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes2008In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 71, no 3, p. 177-183Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To explore the involvement of M-type potassium channels KCNQ2, Q3, and Q5 in the pathogenesis of common idiopathic epilepsies. METHODS: Sequence analysis of the KCNQ2, Q3, and Q5 coding regions was performed in a screening sample consisting of 58 nuclear families with rolandic epilepsy. Subsequently, an association study was conducted for all discovered variants in a case-control sample comprising 459 German patients with idiopathic generalized epilepsy (IGE) and 462 population controls. RESULTS: An in-frame deletion of codon 116 in KCNQ2 (p.Lys116del) and a missense mutation in KCNQ3 (p.Glu299Lys) were detected in two index cases exhibiting rolandic epilepsy and benign neonatal convulsions. Both mutations resulted in reduced potassium current amplitude in Xenopus oocytes. Mutation analysis of families with rolandic epilepsy without neonatal seizures discovered three novel missense variations (KCNQ2 p.Ile592Met, KCNQ3 p.Ala381Val, KCNQ3 p.Pro574Ser). The KCNQ2 p.Ile592Met variant displayed a significant reduction of potassium current amplitude in Xenopus oocytes and was present only once in 552 controls. Both missense variants identified in KCNQ3 (p.Ala381Val and p.Pro574Ser) were present in all affected family members and did not occur in controls, but did not show obvious functional abnormalities. The KCNQ3 missense variant p.Pro574Ser was also detected in 8 of 455 IGE patients but not in 454 controls (p = 0.008). In KCNQ2, a silent single nucleotide polymorphism (rs1801545) was found overrepresented in both epilepsy samples (IGE, p = 0.004). CONCLUSION: Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common idiopathic epilepsy syndromes.

  • 22. Nutt, JG
    et al.
    Deleu, D
    Hanssens, Y
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Jansson, R
    Willows, T
    Remahl, IN
    Long-term 24-hour duodenal infusion of levodopa: Outcome and dose requirements2006In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 66, no 10, p. 1611-1612Article in journal (Other academic)
  • 23.
    Nyrén, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    McLaughlin, Joseph K.
    Yin, Li
    Josefsson, Staffan
    Engkvist, Martin
    Hakelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Blot, William J.
    Adami, Hans-Olov
    Breast implants and risk of neurologic disease: a population-based cohort study in Sweden1998In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 50, no 4, p. 956-961Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine the risk of neurologic disorders among women with breast implants. BACKGROUND: Case reports in the literature have raised concern about a possible link between silicone breast implants and some types of neurologic disorders, but there is a dearth of epidemiologic studies in this area. METHODS: Through the nationwide Swedish hospital discharge register, we identified a population-based cohort of 7433 women with breast implants. A similarly identified cohort of 3351 women who underwent breast reduction surgery served as a comparison. The women were followed from 1972 (or date of breast surgery if it occurred later) through 1993 by means of record linkages and review of inpatient medical records. Ratios of observed to expected numbers, and relative risks (RR) with 95% confidence intervals (CI), were calculated as measures of the risk of neurologic diseases among women with implants. RESULTS: A direct comparison of the exposed (implant) versus comparison (breast reduction) groups, after exclusion of patients with pre-existing disease or incorrect neurologic diagnoses, showed no excess risk among implant patients (RR = 0.8; 95% CI = 0.5 to 1.4). When external rates derived from the background population were used as comparison, we found a small, statistically nonsignificant excess of neurologic disorders both in the breast implant (RR = 1.3; 95% CI = 0.9 to 1.9) and the breast reduction (RR = 1.5; 95% CI = 0.9 to 2.4) cohorts. CONCLUSION: Our results provide no support for the conjecture that breast implants cause neurologic disease.

  • 24. Paloneva, J.
    et al.
    Autti, Taina
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Partanen, J.
    Salonen, Oili
    Puranen, M.
    Hakola, P.
    Haltia, Matti
    CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts2001In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 56, no 11, p. 1552-8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Nasu-Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a genetically heterogeneous disease characterized by a combination of systemic bone cysts and dementia. OBJECTIVE: The authors present a neurologic, neuroradiologic, and neuropathologic analysis of a series of PLOSL patients in which the diagnosis has been confirmed by molecular genetic methods. METHODS: Clinical, neurophysiologic, and imaging follow-up data on eight patients as well as autopsy samples of three patients were analyzed in this study. All eight patients were homozygous for a loss-of-function mutation in the DAP12 gene. RESULTS: In most patients, the disease debuted with pain in ankles and wrists after strain during the third decade, followed by fractures caused by cystic lesions in the bones of the extremities. Frontal lobe syndrome and dementia began to develop by age 30, leading to death by age 40. Neuroimaging disclosed abnormally high and progressively increasing bicaudate ratios and calcifications in the basal ganglia as well as increased signal intensities of the white matter on T2-weighted MR images even before the appearance of clinical neurologic symptoms. Three patients who had undergone autopsies showed an advanced sclerosing leukoencephalopathy with frontal accentuation, widespread activation of microglia, and microvascular changes. CONCLUSIONS: Although PLOSL in most patients manifests by bone fractures, some patients do not show any osseous symptoms and signs before the onset of neurologic manifestations. Consequently, patients with frontal-type dementia of unknown origin should be investigated by x-ray of ankles and wrists. The current results suggest early basal ganglia involvement in PLOSL.

  • 25. Prestia, Annapaola
    et al.
    Caroli, Anna
    van der Flier, Wiesje M.
    Ossenkoppele, Rik
    Van Berckel, Bart
    Barkhof, Frederik
    Teunissen, Charlotte E.
    Wall, Anders E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Carter, Stephen F.
    Scholl, Michael
    Choo, Il Han
    Nordberg, Agneta
    Scheltens, Philip
    Frisoni, Giovanni B.
    Prediction of dementia in MCI patients based on core diagnostic markers for Alzheimer disease2013In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 80, no 11, p. 1048-1056Article in journal (Refereed)
    Abstract [en]

    Objectives: The current model of Alzheimer disease (AD) stipulates that brain amyloidosis biomarkers turn abnormal earliest, followed by cortical hypometabolism, and finally brain atrophy ones. The aim of this study is to provide clinical evidence of the model in patients with mild cognitive impairment (MCI). Methods: A total of 73 patients with MCI from 3 European memory clinics were included. Brain amyloidosis was assessed by CSF A beta 42 concentration, cortical metabolism by an index of temporoparietal hypometabolism on FDG-PET, and brain atrophy by automated hippocampal volume. Patients were divided into groups based on biomarker positivity: 1) A beta 422- FDG-PET- Hippo-, 2) A beta 42+ FDG-PET- Hippo-, 3) A beta 42+ FDG-PET + Hippo-, 4) A beta 42+ FDG-PET+ Hippo+, and 5) any other combination not in line with the model. Measures of validity were prevalence of group 5, increasing incidence of progression to dementia with increasing biological severity, and decreasing conversion time. Results: When patients with MCI underwent clinical follow-up, 29 progressed to dementia, while 44 remained stable. A total of 26% of patients were in group 5. Incident dementia was increasing with greater biological severity in groups 1 to 5 from 4% to 27%, 64%, and 100% (p for trend, 0.0001), and occurred increasingly earlier (p for trend = 0.024). Conclusions: The core biomarker pattern is in line with the current pathophysiologic model of AD. Fully normal and fully abnormal pattern is associated with exceptional and universal development of dementia. Cases not in line might be due to atypical neurobiology or inaccurate thresholds for biomarker (ab) normality. 

  • 26.
    Rönnemaa, E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Zethelius, B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sundelöf, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sundström, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Degerman-Gunnarsson, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lannfelt, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kilander, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Impaired insulin secretion increases the risk of Alzheimer disease2008In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 71, no 14, p. 1046-47Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Subjects with diabetes are reported to have an increased risk of dementia and cognitive impairment. However, the underlying causes remain unknown. We investigated the longitudinal associations between midlife insulin secretion, glucose metabolism, and the subsequent development of Alzheimer disease (AD) and dementia. METHODS: The population-based Uppsala Longitudinal Study of Adult Men started 1970 when the 2,322 participants were 50 years old. Investigation at baseline included determinations of acute insulin response and glucose tolerance using the IV glucose tolerance test and Homeostasis Model Assessment insulin resistance index. During a median follow up of 32 years, 102 participants were diagnosed with AD, 57 with vascular dementia, and 394 with any dementia or cognitive impairment. Associations were analyzed using Cox proportional hazard models. RESULTS: A low insulin response at baseline was associated with a higher cumulative risk of AD (hazard ratio for 1 SD decrease, 1.31; 95% CI, 1.10-1.56) also after adjustment for age, systolic blood pressure, body mass index, serum cholesterol, smoking, education level, and insulin resistance. This association was stronger in subjects without the APOE epsilon4 allele. Impaired glucose tolerance increased the risk of vascular dementia (hazard ratio for 1 SD decrease, 1.45; 95% CI, 1.05-2.00) but not AD. Impaired insulin secretion, glucose intolerance, and estimates of insulin resistance were all associated with higher risk of any dementia and cognitive impairment. CONCLUSIONS: In this longitudinal study, impaired acute insulin response at midlife was associated with an increased risk of Alzheimer disease (AD) up to 35 years later suggesting a causal link between insulin metabolism and the pathogenesis of AD.

  • 27. Schöll, Michael
    et al.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Thordardottir, Steinunn
    Ferreira, Daniel
    Bogdanovic, Nenad
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Almkvist, Ove
    Graff, Caroline
    Nordberg, Agneta
    Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers2012In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, no 3, p. 229-236Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the particular pathology of the Arctic APP (APParc) early-onset familial Alzheimer disease (eoFAD) mutation for the first time in vivo with PET in comparison with other eoFAD mutations and sporadic Alzheimer disease (sAD).

    Methods: We examined 2 APParc mutation carriers together with 5 noncarrier siblings cross-sectionally with C-11-labeled Pittsburgh compound B (PiB) and F-18-fluorodeoxyglucose (FDG) PET, as well as MRI, CSF biomarkers, and neuropsychological tests. Likewise, we examined 7 patients with sAD, 1 carrier of a presenilin 1 (PSEN1) mutation, 1 carrier of the Swedish APP (APPswe) mutation, and 7 healthy controls (HCs).

    Results: Cortical PiB retention was very low in the APParc mutation carriers while cerebral glucose metabolism and CSF levels of A beta(1-42), total and phosphorylated tau were clearly pathologic. This was in contrast to the PSEN1 and APPswe mutation carriers revealing high PiB retention in the cortex and the striatum in combination with abnormal glucose metabolism and CSF biomarkers, and the patients with sAD who showed typically high cortical PiB retention and pathologic CSF levels as well as decreased glucose metabolism when compared with HCs.

    Conclusions: The lack of fibrillar beta-amyloid (A beta) as visualized by PiB PET in APParc mutation carriers suggests, given the reduced glucose metabolism and levels of A beta(1-42) in CSF, that other forms of A beta such as oligomers and protofibrils are important for the pathologic processes leading to clinical Alzheimer disease.

  • 28. Seppala, T. T.
    et al.
    Nerg, O.
    Koivisto, A. M.
    Rummukainen, J.
    Puli, L.
    Zetterberg, H.
    Pyykko, O. T.
    Helisalmi, S.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hiltunen, M.
    Jaaskelainen, J. E.
    Rinne, J.
    Soininen, H.
    Leinonen, V.
    Herukka, S. -K
    CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings2012In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 78, no 20, p. 1568-1575Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD.

    Methods: In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), A beta plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF A beta 42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia.

    Results: The patients with A beta 42 plaques in the cortical biopsy had lower (p = 0.009) CSF A beta 42 levels than those with no A beta plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) A beta 42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest A beta 42 and highest tau and p-tau 181 levels in CSF. The A beta 42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical A beta was independently predicted by the APOE epsilon 4 carrier status and age but not by CSF A beta 42 or tau levels.

    Conclusions: Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF A beta 42 and high CSF tau and p-tau levels, respectively.

  • 29.
    Shahim, Pashtun
    et al.
    Gothenburg Univ, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41124 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden..
    Tegner, Yelverton
    Lulea Univ Technol, Dept Hlth Sci, Div Med Sci, Lulea, Sweden..
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hoeglund, Kina
    Gothenburg Univ, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41124 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden..
    Portelius, Erik
    Gothenburg Univ, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41124 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden..
    Brody, David L.
    Washington Univ, Sch Med, St Louis, MO 63130 USA..
    Blennow, Kaj
    Gothenburg Univ, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41124 Gothenburg, Sweden..
    Zetterberg, Henrik
    Gothenburg Univ, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41124 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden.;UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England..
    Astroglial activation and altered amyloid metabolism in human repetitive concussion2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, no 15, p. 1400-1407Article in journal (Refereed)
    Abstract [en]

    Objective: To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood-brain barrier (BBB) impairment. Methods: A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25-12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (A beta 38, A beta 40, A beta 42, sAPPa, and sAPPb), and BBB function (CSF: serum albumin ratio). Results: Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS.1 year. Athletes with PCS.1 year had higher RPQ scores and number of concussions than athletes with PCS,1 year. Median concentrations of GFAP and YKL-40 were higher in athletes with PCS.1 year compared with controls, although with an overlap between the groups. YKL-40 correlated with RPQ score and the lifetime number of concussions. Athletes with rcTBI had lower concentrations of A beta 40 and A beta 42 than controls. The CSF: serum albumin ratio was unaltered. Conclusions: This study suggests that PCS may be associated with biomarker evidence of astroglial activation and b-amyloid (A beta) dysmetabolism in the brain. There was no clear evidence of Ab deposition as A beta 40 and A beta 42 were reduced in parallel. The CSF: serum albumin ratio was unaltered, suggesting that the BBB is largely intact in PCS.

  • 30. Skillbäck, T
    et al.
    Farahmand, B
    Bartlett, JW
    Rosén, C
    Mattsson, N
    Nägga, K
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Religa, D
    Wimo, A
    Winblad, B
    Rosengren, L
    Schott, JM
    Blennow, K
    Eriksdotter, M
    Zetterberg, H
    CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival2014In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 83, no 21, p. 1945-1953Article in journal (Refereed)
    Abstract [en]

    Objectives: We hypothesized that CSF neurofilament light (NFL) levels would be elevated in dementias with subcortical involvement, including vascular dementia (VaD), but less elevated in dementias primarily affecting gray matter structures, such as Alzheimer disease (AD), and that elevated CSF NFL would correlate with disease severity and shorter survival time irrespective of clinical diagnosis.

    Methods: We included 3,356 individuals with dementia who had CSF NFL analyzed in our laboratory between 2005 and 2012. Clinical diagnoses and Mini-Mental State Examination (MMSE) scores were obtained from the Swedish Dementia Registry, and in selected cases (n = 478), date of death from the Swedish Mortality Registry.

    Results: CSF NFL differed among clinical diagnoses, with the highest levels seen in frontotemporal dementia, VaD, and mixed AD and VaD. Early-onset AD (younger than 65 years) had the lowest levels. High CSF NFL correlated with low MMSE score and short survival time irrespective of diagnosis, and was also particularly evident in AD.

    Conclusions: CSF NFL differs among different neurodegenerative diseases and is especially high in dementias engaging subcortical brain regions, such as VaD and mixed AD and VaD, but also in frontotemporal dementia. The association of high CSF NFL levels with disease severity and short survival supports the notion that high CSF NFL levels indicate more aggressive disease processes.

  • 31.
    Sundelöf, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, J.
    Ingelsson, E.
    Sundström, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Irizarry, M. C.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Rönnemaa, Elina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Degerman-Gunnarsson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hyman, B. T.
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum cystatin C and the risk of Alzheimer disease in elderly men2008In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 71, no 14, p. 1072-1079Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Multiple lines of research suggest that increased cystatin C activity in the brain protects against the development of Alzheimer disease (AD). METHODS: Serum cystatin C levels were analyzed at two examinations of the Uppsala Longitudinal Study of Adult Men, a longitudinal, community-based study of elderly men (age 70 years, n = 1,153 and age 77 years, n = 761, a subset of the age 70 examination). Cox regressions were used to examine associations between serum cystatin C and incident AD. AD cases were identified by cognitive screening and comprehensive medical chart review in all subjects. RESULTS: On follow-up (median 11.3 years), 82 subjects developed AD. At age 70 years, lower cystatin C was associated with higher risk of AD independently of age, APOE4 genotype, glomerular filtration rate, diabetes, hypertension, stroke, cholesterol, body mass index, smoking, education level, and plasma amyloid-beta protein 40 and 42 levels (hazard ratio [HR] for lowest [<1.12 micromol/L] vs highest [>1.30 micromol/L] tertile = 2.67, 95% CI 1.22-5.83, p < 0.02). The results were similar at age 77 years (43 participants developed AD during follow-up). Furthermore, a 0.1-mumol/L decrease of cystatin C between ages 70 and 77 years was associated with a 29% higher risk of incident AD (HR 1.29, 95% CI 1.03-1.63, p < 0.03). CONCLUSIONS: Low levels of serum cystatin C precede clinically manifest Alzheimer disease (AD) in elderly men free of dementia at baseline and may be a marker of future risk of AD. These findings strengthen the evidence for a role for cystatin C in the development of clinical AD.

  • 32. Tajsharghi, H.
    et al.
    Kimber, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Holmgren, D.
    Tulinius, M.
    Oldfors, A.
    Distal arthrogryposis and muscle weakness associated with a beta-tropomyosin mutation2007In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 68, no 10, p. 772-775Article in journal (Refereed)
    Abstract [en]

    Tropomyosin (TM), a sarcomeric thin-filament protein, plays an essential part in muscle contraction by regulating actin-myosin interaction. We describe two patients, a woman and her daughter, with muscle weakness and distal arthrogryposis (DA) type 2B, caused by a heterozygous missense mutation, R133W, in TPM2, the gene encoding beta-TM. Our results demonstrate the involvement of muscle dysfunction in the pathogenesis of DA and the fact that DA2B may be caused by mutations in TPM2.

  • 33. Tomson, Torbjörn
    et al.
    Battino, Dina
    Bonizzoni, Erminio
    Craig, John J
    Lindhout, Dick
    Perucca, Emilio
    Sabers, Anne
    Thomas, Sanjeev V
    Vajda, Frank
    Antiepileptic drugs and intrauterine death: A prospective observational study from EURAP2015In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 85, no 7, p. 580-588Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare the risk of spontaneous abortions and stillbirth associated with maternal use of different antiepileptic drugs (AEDs).

    METHODS: The EURAP registry is an observational international cohort study primarily designed to determine the risk of major congenital malformations (MCMs) after prenatal AED exposure. Using EURAP data, we prospectively monitored pregnancies exposed to the 6 most common AED monotherapies and to polytherapy. Intrauterine death (spontaneous abortion and stillbirth combined) was the primary endpoint.

    RESULTS: Of 7,055 pregnancies exposed to monotherapy with lamotrigine (n = 1,910), carbamazepine (n = 1,713), valproic acid (n = 1,171), levetiracetam (n = 324), oxcarbazepine (n = 262), or phenobarbital (n = 260), and to polytherapy (n = 1,415), 632 ended in intrauterine deaths (592 spontaneous abortions and 40 stillbirths). Rates of intrauterine death were similar across the different monotherapies (8.2%; 95% confidence interval [CI] 7.5%-8.9%), higher with polytherapy (12.1%; 95% CI 10.5%-13.9%), but showed no relationship with AED dose in monotherapy at conception. Multivariable analysis including 11 covariates in addition to the different AED exposures showed that the risk was greater with polytherapy vs monotherapy (risk ratio [RR] 1.38; 95% CI 1.14-1.66), parental history of MCMs (RR 1.92; 1.20-3.07), maternal age (RR 1.06; 1.04-1.07), and number of previous intrauterine deaths (RR 1.09; 1.00-1.19). The risk was greater with early enrollment and decreased with later gestational week at enrollment (RR 0.84; 0.82-0.86).

    CONCLUSIONS: The most important risk factors for intrauterine death in pregnancies of women with epilepsy include maternal exposure to AED polytherapy and the presence of MCMs in at least one of the parents.

  • 34.
    Wiberg, Bernice
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundelöf, Johan E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cognitive function and risk of stroke in elderly men2010In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 74, no 5, p. 379-385Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Vascular risk factors are associated with ischemic changes in the cerebral white matter. We studied the predictive value of cognitive test performance especially related to subcortico-frontal pathways, together with a cognitive screening test, for later incidence of fatal or nonfatal stroke or TIAs and stroke subtypes. METHODS: A sample of 930 70-year-old men without previous stroke/TIA from the community-based Uppsala Longitudinal Study of Adult Men was investigated at baseline using Trail Making Tests (TMT) A and B and the Mini-Mental State Examination (MMSE). RESULTS: During up to 13 years of follow-up, 166 men developed a stroke or TIA; 105 participants had a brain infarction. In Cox proportional hazards analyses adjusting for education, social group, and traditional cardiovascular risk factors, a 1-SD increase in TMT-B time was associated with a higher risk for brain infarction (hazard ratio 1.48, 95% confidence interval 1.11-1.97). The risk of brain infarction was more than threefold higher in the highest (TMT-B = 146-240 s) compared to the lowest (TMT-B = 43-84 s) TMT-B quartile. TMT-A and MMSE results were not consistently related to stroke outcomes. CONCLUSION: Impaired performance in elderly men measured by Trail Making Test B, a cognitive test especially reflecting subcortico-frontal activities, was an independent predictor of subsequent brain infarction in this community-based sample of elderly men. Our results extend previous findings of cognitive decline as an independent predictor of stroke and indicate that the risk of brain infarction is increased already in the subclinical phase of cognitive deficit.

1 - 34 of 34
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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