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  • 1.
    Gauffin, Helena
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Boström, Inger
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Berntsson, Shala Ghaderi
    Uppsala Univ, Sweden.
    Kristoffersson, Anna
    Uppsala Univ, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Characterization of the Increase in Narcolepsy following the 2009 H1N1 Pandemic in Sweden2024In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 13, no 3, article id 652Article in journal (Refereed)
    Abstract [en]

    (1) Background: In the context of the H1N1 pandemic and the Pandemrix vaccination campaign, an increased number of narcolepsy cases were noted in several countries. In Sweden, this phenomenon was attributed to the effect of the Pandemrix vaccination in the first place. Studies from China indicated that narcolepsy could occur as a consequence of the H1N1 infection itself. We performed an analysis of the increase, with a specific interest in age and sex distribution. We also aimed to validate the origin of the excess cases, post hoc. (2) Methods: Data for narcolepsy patients (ICD code G 47.4, both type 1 and type 2) distributed by sex and age at 5-year intervals, annually between 2005 and 2017, were retrieved from the National Patient Register. Information on the total population was collected from the Swedish Population Register. (3) Results: The number of narcolepsy cases increased markedly from 2009 to 2014 compared to the period before 2009. A particular increase in 2011 among children and teenagers was observed. The sex ratio did not change significantly during the study period. (4) Conclusions: Our results support an association between the increased prevalence of narcolepsy cases and Pandemrix vaccination, but the effect of the virus itself cannot be ruled out as a contributing factor.

  • 2.
    Korman, Maria
    et al.
    Ariel Univ, Israel.
    Zarina, Daria
    Ariel Univ, Israel.
    Tkachev, Vadim
    Ariel Univ, Israel.
    Merikanto, Ilona
    Univ Helsinki, Finland; Orton Orthopaed Hosp, Finland.
    Bjorvatn, Bjorn
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Bjelajac, Adrijana Koscec
    Inst Med Res & Occupat Hlth, Croatia.
    Penzel, Thomas
    Charite Univ Med Berlin, Germany.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Benedict, Christian
    Uppsala Univ, Sweden.
    Chan, Ngan Yin
    Chinese Univ Hong Kong, Peoples R China.
    Wing, Yun Kwok
    Chinese Univ Hong Kong, Peoples R China.
    Dauvilliers, Yves
    Univ Montpellier, France.
    Morin, Charles M.
    Univ Laval, Canada.
    Matsui, Kentaro
    Natl Ctr Hosp, Japan.
    Nadorff, Michael
    Mississippi State Univ, MS USA.
    Bolstad, Courtney J.
    Mississippi State Univ, MS USA; South Texas Vet Hlth Care Syst, TX USA.
    Chung, Frances
    Univ Toronto, Canada.
    Mota-Rolim, Sergio
    Univ Fed Rio Grande do Norte, Brazil; Univ Fed Rio Grande do Norte, Brazil.
    De Gennaro, Luigi
    Sapienza Univ Rome, Italy; IRCCS Fdn Santa Lucia, Italy.
    Plazzi, Giuseppe
    Irccs Ist Sci Neurol Bologna, Italy; Univ Modena & Reggio Emilia, Italy.
    Yordanova, Juliana
    Bulgarian Acad Sci, Bulgaria.
    Holzinger, Brigitte
    Med Univ Vienna, Austria.
    Partinen, Markku
    Univ Helsinki, Finland; Terveystalo Healthcare Serv, Finland.
    Reis, Catia
    Univ Catolica Portuguesa, Portugal; Univ Lisbon, Portugal.
    Estimation bias and agreement limits between two common self-report methods of habitual sleep duration in epidemiological surveys2024In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 3420Article in journal (Refereed)
    Abstract [en]

    Accurate measurement of habitual sleep duration (HSD) is crucial for understanding the relationship between sleep and health. This study aimed to assess the bias and agreement limits between two commonly used short HSD self-report methods, considering sleep quality (SQ) and social jetlag (SJL) as potential predictors of bias. Data from 10,268 participants in the International COVID Sleep Study-II (ICOSS-II) were used. Method-Self and Method-MCTQ were compared. Method-Self involved a single question about average nightly sleep duration (HSDself), while Method-MCTQ estimated HSD from reported sleep times on workdays (HSDMCTQwork) and free days (HSDMCTQfree). Sleep quality was evaluated using a Likert scale and the Insomnia Severity Index (ISI) to explore its influence on estimation bias. HSDself was on average 42.41 +/- 67.42 min lower than HSDMCTQweek, with an agreement range within +/- 133 min. The bias and agreement range between methods increased with poorer SQ. HSDMCTQwork showed less bias and better agreement with HSDself compared to HSDMCTQfree. Sleep duration irregularity was - 43.35 +/- 78.26 min on average. Subjective sleep quality predicted a significant proportion of variance in HSDself and estimation bias. The two methods showed very poor agreement and a significant systematic bias, both worsening with poorer SQ. Method-MCTQ considered sleep intervals without adjusting for SQ issues such as wakefulness after sleep onset but accounted for sleep irregularity and sleeping in on free days, while Method-Self reflected respondents' interpretation of their sleep, focusing on their sleep on workdays. Including an SQ-related question in surveys may help bidirectionally adjust the possible bias and enhance the accuracy of sleep-health studies.

  • 3.
    Bolstad, Courtney J.
    et al.
    Mississippi State Univ, MS USA; South Texas Vet Hlth Care Syst, TX 78229 USA.
    Holzinger, Brigitte
    Inst Consciousness & Dream Res, Austria; Med Univ Vienna, Austria.
    Scarpelli, Serena
    Univ Rome, Italy.
    De Gennaro, Luigi
    Univ Rome, Italy; IRCCS Fdn Santa Lucia, Italy.
    Yordanova, Juliana
    Bulgarian Acad Sci, Bulgaria.
    Koumanova, Silvia
    Bulgarian Acad Sci, Bulgaria.
    Mota-Rolim, Sergio
    Univ Fed Rio Grande do Norte, Brazil.
    Benedict, Christian
    Uppsala Univ, Sweden.
    Bjorvatn, Bjorn
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Chan, Ngan Yin
    Chinese Univ Hong Kong, Peoples R China.
    Chung, Frances
    Univ Toronto, Canada.
    Dauvilliers, Yves
    Univ Montpellier, France.
    Espie, Colin A.
    Univ Oxford, England; Univ Oxford, England.
    Inoue, Yuichi
    Tokyo Med Univ, Japan.
    Korman, Maria
    Ariel Univ, Israel.
    Koscec Bjelajac, Adrijana
    Inst Med Res & Occupat Hlth, Croatia.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Matsui, Kentaro
    Natl Ctr Hosp, Japan.
    Merikanto, Ilona
    Univ Helsinki, Finland; Orton Orthopaed Hosp, Finland.
    Morin, Charles M.
    Laval Univ, Canada; Ctr Rech CERVO, Canada.
    Partinen, Markku
    Terveystalo Healthcare, Finland; Univ Helsinki, Finland.
    Penzel, Thomas
    Charite Univ Med Berlin, Germany.
    Plazzi, Giuseppe
    Univ Modena & Reggio Emilia, Italy; IRCCS Ist Sci Neurol Bologna, Italy.
    Reis, Catia
    Univ Catolica Portuguesa, Portugal; Univ Lisbon, Portugal.
    Ross, Biserka
    Inst Med Res & Occupat Hlth, Croatia.
    Wing, Yun Kwok
    Chinese Univ Hong Kong, Peoples R China.
    Nadorff, Michael R.
    Mississippi State Univ, MS USA; Baylor Coll Med, TX USA.
    Nightmare frequency is a risk factor for suicidal ideation during the COVID-19 pandemic2024In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869Article in journal (Refereed)
    Abstract [en]

    The association between nightmare frequency (NMF) and suicidal ideation (SI) is well known, yet the impact of the COVID-19 pandemic on this relation is inconsistent. This study aimed to investigate changes in NMF, SI, and their association during the COVID-19 pandemic. Data were collected in 16 countries using a harmonised questionnaire. The sample included 9328 individuals (4848 women; age M[SD] = 46.85 [17.75] years), and 17.60% reported previous COVID-19. Overall, SI was significantly 2% lower during the pandemic vs. before, and this was consistent across genders and ages. Most countries/regions demonstrated decreases in SI during this pandemic, with Austria (-9.57%), Sweden (-6.18%), and Bulgaria (-5.14%) exhibiting significant declines in SI, but Italy (1.45%) and Portugal (2.45%) demonstrated non-significant increases. Suicidal ideation was more common in participants with long-COVID (21.10%) vs. short-COVID (12.40%), though SI did not vary by COVID-19 history. Nightmare frequency increased by 4.50% during the pandemic and was significantly higher in those with previous COVID-19 (14.50% vs. 10.70%), during infection (23.00% vs. 8.10%), and in those with long-COVID (18.00% vs. 8.50%). The relation between NMF and SI was not significantly stronger during the pandemic than prior (rs = 0.18 vs. 0.14; z = 2.80). Frequent nightmares during the pandemic increased the likelihood of reporting SI (OR = 1.57, 95% CI 1.20-2.05), while frequent dream recall during the pandemic served a protective effect (OR = 0.74, 95% CI 0.59-0.94). These findings have important implications for identifying those at risk of suicide and may offer a potential pathway for suicide prevention.

  • 4.
    Matsui, Kentaro
    et al.
    Natl Ctr Hosp, Japan.
    Chung, Frances
    Univ Toronto, Canada.
    Bjelajac, Adrijana Koscec
    Inst Med Res & Occupat Hlth, Croatia.
    Merikanto, Ilona
    Univ Helsinki, Finland; Orton Orthopaed Hosp, Finland.
    Korman, Maria
    Ariel Univ, Israel.
    Mota-Rolim, Sergio
    Univ Fed Rio Grande do Norte, Brazil.
    Cunha, Ana Suely
    Univ Potiguar, Brazil.
    Bjorvatn, Bjorn
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Xue, Pei
    Uppsala Univ, Sweden.
    Benedict, Christian
    Uppsala Univ, Sweden.
    Morin, Charles M.
    Univ Laval, Canada.
    Espie, Colin A.
    Univ Oxford, England.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Penzel, Thomas
    Charite, Germany.
    De Gennaro, Luigi
    Sapienza Univ Rome, Italy; IRCCS, Italy.
    Holzinger, Brigitte
    Med Univ Vienna, Austria.
    Hrubos-Strom, Harald
    Akershus Univ Hosp, Norway; Univ Oslo, Norway.
    Leger, Damien
    Univ Paris Cite, France; Hop Hotel Dieu, France.
    Bolstad, Courtney J.
    Mississippi State Univ, MS USA; South Texas Vet Hlth Care Syst, TX USA.
    Nadorff, Michael R.
    Mississippi State Univ, MS USA.
    Plazzi, Giuseppe
    IRCCS Ist Sci Neurol Bologna, Italy; Univ Modena & Reggio Emilia, Italy.
    Reis, Catia
    Univ Catolica Portuguesa, Portugal; Univ Lisbon, Portugal.
    Chan, Ngan Yin
    Chinese Univ Hong Kong, Peoples R China.
    Wing, Yun Kwok
    Chinese Univ Hong Kong, Peoples R China.
    Yordanova, Juliana
    Bulgarian Acad Sci, Bulgaria.
    Dauvilliers, Yves
    Univ Montpellier, France.
    Partinen, Markku
    Univ Helsinki, Finland; Terveystalo Healthcare Serv, Finland.
    Inoue, Yuichi
    Japan Somnol Ctr, Japan; Tokyo Med Univ, Japan.
    Associations between changes in habitual sleep duration and lower self-rated health among COVID-19 survivors: findings from a survey across 16 countries/regions2023In: BMC Public Health, E-ISSN 1471-2458, Vol. 23, no 1, article id 2352Article in journal (Refereed)
    Abstract [en]

    Background Self-rated health (SRH) is widely recognized as a clinically significant predictor of subsequent mortality risk. Although COVID-19 may impair SRH, this relationship has not been extensively examined. The present study aimed to examine the correlation between habitual sleep duration, changes in sleep duration after infection, and SRH in subjects who have experienced SARS-CoV-2 infection.Methods Participants from 16 countries participated in the International COVID Sleep Study-II (ICOSS-II) online survey in 2021. A total of 10,794 of these participants were included in the analysis, including 1,509 COVID-19 individuals (who reported that they had tested positive for COVID-19). SRH was evaluated using a 0-100 linear visual analog scale. Habitual sleep durations of < 6 h and > 9 h were defined as short and long habitual sleep duration, respectively. Changes in habitual sleep duration after infection of <= -2 h and >= 1 h were defined as decreased or increased, respectively.Results Participants with COVID-19 had lower SRH scores than non-infected participants, and those with more severe COVID-19 had a tendency towards even lower SRH scores. In a multivariate regression analysis of participants who had experienced COVID-19, both decreased and increased habitual sleep duration after infection were significantly associated with lower SRH after controlling for sleep quality (beta = -0.056 and -0.058, respectively, both p < 0.05); however, associations between current short or long habitual sleep duration and SRH were negligible. Multinomial logistic regression analysis showed that decreased habitual sleep duration was significantly related to increased fatigue (odds ratio [OR] = 1.824, p < 0.01), shortness of breath (OR = 1.725, p < 0.05), diarrhea/nausea/vomiting (OR = 2.636, p < 0.01), and hallucinations (OR = 5.091, p < 0.05), while increased habitual sleep duration was significantly related to increased fatigue (OR = 1.900, p < 0.01).Conclusions Changes in habitual sleep duration following SARS-CoV-2 infection were associated with lower SRH. Decreased or increased habitual sleep duration might have a bidirectional relation with post-COVID-19 symptoms. Further research is needed to better understand the mechanisms underlying these relationships for in order to improve SRH in individuals with COVID-19.

  • 5.
    Berntsson, Shala Ghaderi
    et al.
    Uppsala Univ, Sweden.
    Matsson, Hans
    Uppsala Univ, Sweden; Uppsala Univ Hosp, Sweden.
    Kristoffersson, Anna
    Uppsala Univ, Sweden.
    Niemela, Valter
    Uppsala Univ, Sweden.
    van Duyvenvoorde, Hermine A.
    Leiden Univ, Netherlands.
    Richel-van Assenbergh, Cindy
    Leiden Univ, Netherlands.
    van der Klift, Heleen M.
    Leiden Univ, Netherlands.
    Casar-Borota, Olivera
    Uppsala Univ, Sweden; Uppsala Univ Hosp, Sweden.
    Frykholm, Carina
    Uppsala Univ, Sweden; Uppsala Univ Hosp, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Case report: a novel deep intronic splice-altering variant in DMD as a cause of Becker muscular dystrophy2023In: Frontiers in Genetics, E-ISSN 1664-8021, Vol. 14, article id 1226766Article in journal (Refereed)
    Abstract [en]

    We present the case of a male patient who was ultimately diagnosed with Becker muscular dystrophy (BMD; MIM# 300376) after the onset of muscle weakness in his teens progressively led to significant walking difficulties in his twenties. A genetic diagnosis was pursued but initial investigation revealed no aberrations in the dystrophin gene (DMD), although immunohistochemistry and Western blot analysis suggested the diagnosis of dystrophinopathy. Eventually, after more than 10 years, an RNA analysis captured abnormal splicing where 154 nucleotides from intron 43 were inserted between exon 43 and 44 resulting in a frameshift and a premature stop codon. Normal splicing of the DMD gene was also observed. Additionally, a novel variant c.6291-13537A>G in DMD was confirmed in the genomic DNA of the patient. The predicted function of the variant aligns with the mRNA results. To conclude, we here demonstrate that mRNA analysis can guide the diagnosis of non-coding genetic variants in DMD.

  • 6.
    Lafta, Muataz S.
    et al.
    Uppsala Univ, Sweden.
    Sokolov, Aleksandr V.
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Ericson, Hans
    Uppsala Univ, Sweden.
    Schioeth, Helgi B.
    Uppsala Univ, Sweden.
    Abu Hamdeh, Sami
    Uppsala Univ, Sweden; Uppsala Univ Hosp, Sweden.
    Exploring biomarkers in trigeminal neuralgia patients operated with microvascular decompression: A comparison with multiple sclerosis patients and non-neurological controls2023In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149Article in journal (Refereed)
    Abstract [en]

    BackgroundTrigeminal neuralgia (TN) is a severe facial pain condition often associated with a neurovascular conflict. However, neuroinflammation has also been implicated in TN, as it frequently co-occurs with multiple sclerosis (MS).MethodsWe analysed protein expression levels of TN patients compared to MS patients and controls. Proximity Extension Assay technology was used to analyse the levels of 92 proteins with the Multiplex Neuro-Exploratory panel provided by SciLifeLab, Uppsala, Sweden. Serum and CSF samples were collected from TN patients before (n = 33 and n = 27, respectively) and after (n = 28 and n = 8, respectively) microvascular decompression surgery. Additionally, we included samples from MS patients (n = 20) and controls (n = 20) for comparison.ResultsIn both serum and CSF, several proteins were found increased in TN patients compared to either MS patients, controls, or both, including EIF4B, PTPN1, EREG, TBCB, PMVK, FKBP5, CD63, CRADD, BST2, CD302, CRIP2, CCL27, PPP3R1, WWP2, KLB, PLA2G10, TDGF1, SMOC1, RBKS, LTBP3, CLSTN1, NXPH1, SFRP1, HMOX2, and GGT5. The overall expression of the 92 proteins in postoperative TN samples seems to shift towards the levels of MS patients and controls in both serum and CSF, as compared to preoperative samples. Interestingly, there was no difference in protein levels between MS patients and controls.ConclusionsWe conclude that TN patients showed increased serum and CSF levels of specific proteins and that successful surgery normalizes these protein levels, highlighting its potential as an effective treatment. However, the similarity between MS and controls challenges the idea of shared pathophysiology with TN, suggesting distinct underlying mechanisms in these conditions.SignificanceThis study advances our understanding of trigeminal neuralgia (TN) and its association with multiple sclerosis (MS). By analysing 92 protein biomarkers, we identified distinctive molecular profiles in TN patients, shedding light on potential pathophysiological mechanisms. The observation that successful surgery normalizes many protein levels suggests a promising avenue for TN treatment. Furthermore, the contrasting protein patterns between TN and MS challenge prevailing assumptions of similarity between the two conditions and point to distinct pathophysiological mechanisms.

  • 7.
    Ahmadpour, Doryaneh
    et al.
    Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala. Chalmers Univ Technol, Sweden.
    Kristoffersson, Anna
    Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Fredrikson, Mats
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences, Forum Östergötland.
    Link, Yumin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Eriksson, Anne
    Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Iacobaeus, Ellen
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Uppsala Univ, Sweden.
    Haghighi, Sara
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Inventory study of an early pandemic COVID-19 cohort in South-Eastern Sweden, focusing on neurological manifestations2023In: PLOS ONE, E-ISSN 1932-6203, Vol. 18, no 1, article id e0280376Article in journal (Refereed)
    Abstract [en]

    BackgroundNeurological manifestations in patients with COVID-19 have been reported previously as outcomes of the infection.The purpose of current study was to investigate the occurrence of neurological signs and symptoms in COVID-19 patients, in the county of ostergotland in southeastern Sweden. MethodsThis is a retrospective, observational cohort study. Data were collected between March 2020 and June 2020. Information was extracted from medical records by a trained research assistant and physician and all data were validated by a senior neurologist. ResultsSeventy-four percent of patients developed at least one neurological symptom during the acute phase of the infection. Headache (43%) was the most common neurological symptom, followed by anosmia and/or ageusia (33%), confusion (28%), hallucinations (17%), dizziness (16%), sleep disorders in terms of insomnia and OSAS (Obstructive Sleep Apnea) (9%), myopathy and neuropathy (8%) and numbness and tingling (5%). Patients treated in the ICU had a higher male presentation (73%). Several risk factors in terms of co-morbidities, were identified. Hypertension (54.5%), depression and anxiety (51%), sleep disorders in terms of insomnia and OSAS (30%), cardiovascular morbidity (28%), autoimmune diseases (25%), chronic lung diseases (24%) and diabetes mellitus type 2 (23%) founded as possible risk factors. ConclusionNeurological symptoms were found in the vast majority (74%) of the patients. Accordingly, attention to neurological, mental and sleep disturbances is warranted with involvement of neurological expertise, in order to avoid further complications and long-term neurological effect of COVID-19. Furthermore, risk factors for more severe COVID-19, in terms of possible co-morbidities that identified in this study should get appropriate attention to optimizing treatment strategies in COVID-19 patients.

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  • 8.
    Xue, Pei
    et al.
    Uppsala Univ, Sweden.
    Merikanto, Ilona
    Univ Helsinki, Finland.
    Chung, Frances
    Univ Toronto, Canada.
    Morin, Charles M.
    Univ Laval, Canada.
    Espie, Colin
    Univ Oxford, England.
    Bjorvatn, Bjorn
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Cedernaes, Jonathan
    Uppsala Univ, Sweden; Uppsala Univ, Sweden; Northwestern Univ, IL USA.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Penzel, Thomas
    Charite, Germany.
    De Gennaro, Luigi
    Sapienza Univ Rome, Italy; IRCCS Fdn Santa Lucia, Italy.
    Holzinger, Brigitte
    Med Univ Vienna, Austria.
    Matsui, Kentaro
    Natl Ctr Hosp, Japan.
    Hrubos-Strom, Harald
    Akershus Univ Hosp, Norway; Univ Oslo, Norway.
    Korman, Maria
    Ariel Univ, Israel.
    Leger, Damien
    Hop Hotel Dieu Paris, France; Univ Paris, France.
    Mota-Rolim, Sergio
    Onofre Lopes Univ Hosp, Brazil; Univ Fed Rio Grande do Norte, Brazil.
    Bolstad, Courtney J.
    Mississippi State Univ, MS USA.
    Nadorff, Michael
    Mississippi State Univ, MS USA.
    Plazzi, Giuseppe
    IRCCS Ist Sci Neurol Bologna, Italy; Univ Modena & Reggio Emilia, Italy.
    Reis, Catia
    Univ Catolica Portuguesa, Portugal; Univ Lisbon, Portugal; Univ Lisbon, Portugal.
    Chan, Rachel Ngan Yin
    Chinese Univ Hong Kong, Peoples R China.
    Wing, Yun Kwok
    Chinese Univ Hong Kong, Peoples R China.
    Yordanova, Juliana
    Bulgarian Acad Sci, Bulgaria.
    Bjelajac, Adrijana Koscec
    Inst Med Res & Occupat Hlth, Croatia.
    Inoue, Yuichi
    Tokyo Med Univ, Japan; Japan Somnol Ctr, Japan.
    Partinen, Markku
    Univ Helsinki, Finland; Terveystalo Healthcare Serv, Finland.
    Dauvilliers, Yves
    Univ Montpellier, France.
    Benedict, Christian
    Uppsala Univ, Sweden.
    Persistent short nighttime sleep duration is associated with a greater post-COVID risk in fully mRNA-vaccinated individuals2023In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, no 1, article id 32Article in journal (Refereed)
    Abstract [en]

    Short nighttime sleep duration impairs the immune response to virus vaccination, and long nighttime sleep duration is associated with poor health status. Thus, we hypothesized that short (<6 h) and long (>9 h) nighttime sleepers have a higher post-COVID risk than normal nighttime sleepers, despite two doses of mRNA vaccine (which has previously been linked to lower odds of long-lasting COVID-19 symptoms). Post-COVID was defined as experiencing at least one core COVID-19 symptom for at least three months (e.g., shortness of breath). Multivariate logistic regression adjusting for age, sex, BMI, and other factors showed in 9717 respondents (age span 18-99) that two mRNA vaccinations lowered the risk of suffering from post-COVID by about 21% (p < 0.001). When restricting the analysis to double-vaccinated respondents (n = 5918), short and long sleepers exhibited a greater post-COVID risk than normal sleepers (adjusted OR [95%-CI], 1.56 [1.29, 1.88] and 1.87 [1.32, 2.66], respectively). Among respondents with persistent sleep duration patterns during the pandemic compared to before the pandemic, short but not long sleep duration was significantly associated with the post-COVID risk (adjusted OR [95%-CI], 1.59 [1.24, 2.03] and 1.18 [0.70, 1.97], respectively). No significant association between sleep duration and post-COVID symptoms was observed in those reporting positive SARS-CoV-2 test results (n = 538). Our findings suggest that two mRNA vaccinations against SARS-CoV-2 are associated with a lower post-COVID risk. However, this protection may be less pronounced among those sleeping less than 6 h per night. Our findings warrant replication in cohorts with individuals with confirmed SARS-CoV-2 infection.

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  • 9.
    Bjorvatn, Bjorn
    et al.
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Merikanto, Ilona
    Univ Helsinki, Finland; Orton Orthopaed Hosp, Finland.
    Reis, Catia
    Univ Catolica Portuguesa, Portugal; Fac Med Lisbon, Portugal.
    Korman, Maria
    Ariel Univ, Israel.
    Bjelajac, Adrijana Koscec
    Inst Med Res & Occupat Hlth, Croatia.
    Holzinger, Brigitte
    Med Univ Vienna, Austria.
    De Gennaro, Luigi
    Sapienza Univ Rome, Italy; IRCCS Fdn Santa Lucia, Italy.
    Wing, Yun Kwok
    Chinese Univ Hong Kong, Peoples R China.
    Morin, Charles M.
    Univ Laval, Canada.
    Espie, Colin A.
    Univ Oxford, England.
    Benedict, Christian
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Uppsala Univ, Sweden.
    Matsui, Kentaro
    Natl Ctr Hosp, Japan.
    Hrubos-Strom, Harald
    Akershus Univ Hosp, Norway; Univ Oslo, Norway.
    Mota-Rolim, Sergio
    Univ Fed Rio Grande do Norte, Brazil; Univ Fed Rio Grande do Norte, Brazil.
    Nadorff, Michael R.
    Mississippi State Univ, MS USA.
    Plazzi, Giuseppe
    IRCCS Ist Sci Neurol Bologna, Italy; Univ Modena & Reggio Emilia, Italy.
    Chan, Rachel Ngan Yin
    Chinese Univ Hong Kong, Peoples R China.
    Partinen, Markku
    Univ Helsinki, Finland; Helsinki Sleep Clin, Finland.
    Dauvilliers, Yves
    Univ Montpellier, France.
    Chung, Frances
    Univ Hlth Network, Canada.
    Forthun, Ingeborg
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Shift workers are at increased risk of severe COVID-19 compared with day workers: Results from the international COVID sleep study (ICOSS) of 7141 workers2023In: Chronobiology International, ISSN 0742-0528, E-ISSN 1525-6073, Vol. 40, no 2, p. 114-122Article in journal (Refereed)
    Abstract [en]

    The present study had two main aims. First, to investigate whether shift/night workers had a higher prevalence and severity of COVID-19 compared with day workers. Second, to investigate whether people regularly working in face-to-face settings during the pandemic exhibited a higher prevalence and severity of COVID-19 compared with those having no need to be in close contact with others at work. Data consisted of 7141 workers from 15 countries and four continents who participated in the International COVID Sleep Study-II (ICOSS-II) between May and December 2021. The associations between work status and a positive COVID-19 test and several indications of disease severity were tested with chi-square tests and logistic regressions adjusted for relevant confounders. In addition, statistical analyses were conducted for the associations between face-to-face work and COVID-19 status. Results showed that shift/night work was not associated with an increased risk of COVID-19 compared to day work. Still, shift/night workers reported higher odds for moderate to life-threatening COVID-19 (adjusted odds ratio (aOR) = 2.71, 95%-confidence interval = 1.23-5.95) and need for hospital care (aOR = 5.66, 1.89-16.95). Face-to-face work was associated with an increased risk of COVID-19 (aOR = 1.55, 1.12-2.14) but not with higher disease severity. In conclusion, shift/night work was not associated with an increased risk of COVID-19, but when infected, shift/night workers reported more severe disease. Impaired sleep and circadian disruption commonly seen among shift/night workers may be mediating factors. Working face-to-face increased the risk of COVID-19, likely due to increased exposure to the virus. However, face-to-face work was not associated with increased disease severity.

  • 10.
    Merikanto, Ilona
    et al.
    Univ Helsinki, Finland; Finnish Inst Hlth & Welf, Finland; Orton Orthopaed Hosp, Finland.
    Dauvilliers, Yves
    Univ Montpellier, France.
    Chung, Frances
    Univ Hlth Network, Canada.
    Wing, Yun Kwok
    Chinese Univ Hong Kong, Peoples R China.
    De Gennaro, Luigi
    Sapienza Univ Rome, Italy; IRCCS Fdn Santa Lucia, Italy.
    Holzinger, Brigitte
    Med Univ Vienna, Austria.
    Bjorvatn, Bjorn
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Morin, Charles M.
    Univ Laval, Canada.
    Penzel, Thomas
    Charite, Germany.
    Benedict, Christian
    Uppsala Univ, Sweden.
    Bjelajac, Adrijana Koscec
    Inst Med Res & Occupat Hlth, Croatia.
    Chan, Ngan Yin
    Chinese Univ Hong Kong, Peoples R China.
    Espie, Colin A.
    Univ Oxford, England.
    Hrubos-Strom, Harald
    Akershus Univ Hosp, Norway; Univ Oslo, Norway.
    Inoue, Yuichi
    Tokyo Med Univ, Japan; Japan Somnol Ctr, Japan.
    Korman, Maria
    Ariel Univ, Israel.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Leger, Damien
    Hop Hotel Dieu de Paris, France; Univ Paris, France.
    Matsui, Kentaro
    Natl Ctr Hosp, Japan.
    Mota-Rolim, Sergio
    Univ Fed Rio Grande do Norte, Brazil; Univ Fed Rio Grande do Norte, Brazil.
    Nadorff, Michael R.
    Mississippi State Univ, MS 39762 USA.
    Plazzi, Giuseppe
    IRCCS Ist Sci Neurol Bologna, Italy; Univ Modena & Reggio Emilia, Italy.
    Reis, Catia
    Univ Catolica Portuguese, Portugal; Univ Lisbon, Portugal; Univ Lisbon, Portugal.
    Yordanova, Juliana
    Bulgarian Acad Sci, Bulgaria.
    Partinen, Markku
    Univ Helsinki, Finland; Terveystalo Healthcare, Finland.
    Sleep symptoms are essential features of long-COVID - Comparing healthy controls with COVID-19 cases of different severity in the international COVID sleep study (ICOSS-II)2023In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 32, no 1, article id e13754Article in journal (Refereed)
    Abstract [en]

    Many people report suffering from post-acute sequelae of COVID-19 or "long-COVID", but there are still open questions on what actually constitutes long-COVID and how prevalent it is. The current definition of post-acute sequelae of COVID-19 is based on voting using the Delphi-method by the WHO post-COVID-19 working group. It emphasizes long-lasting fatigue, shortness of breath and cognitive dysfunction as the core symptoms of post-acute sequelae of COVID-19. In this international survey study consisting of 13,628 subjects aged 18-99 years from 16 countries of Asia, Europe, North America and South America (May-Dec 2021), we show that post-acute sequelae of COVID-19 symptoms were more prevalent amongst the more severe COVID-19 cases, i.e. those requiring hospitalisation for COVID-19. We also found that long-lasting sleep symptoms are at the core of post-acute sequelae of COVID-19 and associate with the COVID-19 severity when COVID-19 cases are compared with COVID-negative cases. Specifically, fatigue (61.3%), insomnia symptoms (49.6%) and excessive daytime sleepiness (35.8%) were highly prevalent amongst respondents reporting long-lasting symptoms after hospitalisation for COVID-19. Understanding the importance of sleep-related symptoms in post-acute sequelae of COVID-19 has a clinical relevance when diagnosing and treating long-COVID.

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  • 11.
    Chen, Si-Jing
    et al.
    Univ Laval, Canada; Chinese Univ Hong Kong, Peoples R China.
    Morin, Charles M.
    Univ Laval, Canada.
    Ivers, Hans
    Univ Laval, Canada.
    Wing, Yun Kwok
    Chinese Univ Hong Kong, Peoples R China.
    Partinen, Markku
    Univ Helsinki, Finland; Terveystalo Healthcare, Finland.
    Merikanto, Ilona
    Univ Helsinki, Finland.
    Holzinger, Brigitte
    Med Univ Vienna, Austria.
    Espie, Colin A.
    Univ Oxford, England.
    De Gennaro, Luigi
    Univ Roma La Sapienza, Italy; IRCCS Fdn Santa Lucia, Italy.
    Dauvilliers, Yves
    Univ Montpellier, France.
    Chung, Frances
    Univ Toronto, Canada.
    Yordanova, Juliana
    Bulgarian Acad Sci, Bulgaria.
    Vidovic, Domagoj
    Univ Psychiat Hosp Vrapce, Croatia.
    Reis, Catia
    Univ Catolica Portuguesa, Portugal; Univ Lisbon, Portugal; Univ Lisbon, Portugal; IRCCS Ist Sci Neurol Bologna, Italy.
    Plazzi, Giuseppe
    Univ Modena & Reggio Emilia, Italy.
    Penzel, Thomas
    Charite Univ Med Berlin, Germany.
    Nadorff, Michael R.
    Mississippi State Univ, MS USA.
    Matsui, Kentaro
    Natl Ctr Hosp, Japan.
    Mota-Rolim, Sergio
    Univ Fed Rio Grande do Norte, Brazil.
    Leger, Damien
    Ctr Sommeil & Vigilance, France; Univ Paris Cite, France.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Korman, Maria
    Ariel Univ, Israel.
    Inoue, Yuichi
    Tokyo Med Univ, Japan; Inst Neuropsychiat, Japan.
    Hrubos-Strom, Harald
    Akershus Univ Hosp, Norway; Univ Oslo, Norway.
    Chan, Ngan Yin
    Chinese Univ Hong Kong, Peoples R China.
    Bjelajac, Adrijana Koscec
    Inst Med Res & Occupat Hlth, Croatia.
    Benrdict, Christian
    Uppsala Univ, Sweden.
    Bjorvatn, Bjorn
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    The association of insomnia with long COVID: An international collaborative study (ICOSS-II)2023In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 112, p. 216-222Article in journal (Refereed)
    Abstract [en]

    Objective: There is evidence of a strong association between insomnia and COVID-19, yet few studies have examined the relationship between insomnia and long COVID. This study aimed to investigate whether COVID-19 patients with pre-pandemic insomnia have a greater risk of developing long COVID and whether long COVID is in turn associated with higher incident rates of insomnia symptoms after infection.Methods: Data were collected cross-sectionally (May-Dec 2021) as part of an international collaborative study involving participants from 16 countries. A total of 2311 participants (18-99 years old) with COVID-19 provided valid responses to a web-based survey about sleep, insomnia, and health-related variables. Log-binomial regression was used to assess bidirectional associations between insomnia and long COVID. Analyses were adjusted for age, sex, and health conditions, including sleep apnea, attention and memory problems, chronic fatigue, depression, and anxiety.Results: COVID-19 patients with pre-pandemic insomnia showed a higher risk of developing long COVID than those without pre-pandemic insomnia (70.8% vs 51.4%; adjusted relative risk [RR]: 1.33, 95% confidence in-terval [CI]: 1.07-1.65). Among COVID-19 cases without pre-pandemic insomnia, the rates of incident insomnia symptoms after infection were 24.1% for short COVID cases and 60.6% for long COVID cases (p < .001). Compared with short COVID cases, long COVID cases were associated with an increased risk of developing insomnia symptoms (adjusted RR: 2.00; 95% CI: 1.50-2.66).Conclusions: The findings support a bidirectional relationship between insomnia and long COVID. These findings highlight the importance of addressing sleep and insomnia in the prevention and management of long COVID.

  • 12.
    Link, Yumin
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Yang, Ge
    Sun Yat sen Univ, Peoples R China.
    Gustafsson, Greta
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Gauffin, Helena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Mirabelli, Pierfrancesco
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Link, Hans
    Karolinska Inst, Sweden.
    The Importance of Optical Coherence Tomography in the Diagnosis of Atypical or Subclinical Optic Neuritis: A Case Series Study2023In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 12, no 4, article id 1309Article in journal (Refereed)
    Abstract [en]

    Background: Optic neuritis (ON) is an inflammatory condition of the optic nerve. ON is associated with development of demyelinating diseases of the central nervous system (CNS). CNS lesions visualized by magnetic resonance imaging (MRI) and the finding of oligoclonal IgG bands (OB) in the cerebrospinal fluid (CSF) are used to stratify the risk of MS after a "first" episode of ON. However, the diagnosis of ON in absence of typical clinical manifestations can be challenging. Methods and Materials: Here we present three cases with changes in the optic nerve and ganglion cell layer in the retina over the disease course. (1) A 34-year-old female with a history of migraine and hypertension had suspect amaurosis fugax (transient vision loss) in the right eye. This patient developed MS four years later. Optical coherence tomography (OCT) showed dynamic changes of the thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) over time. (2) A 29-year-old male with spastic hemiparesis and lesions in the spinal cord and brainstem. Six years later he showed bilateral subclinical ON identified using OCT, visual evoked potentials (VEP) and MRI. The patient fulfilled diagnosis criteria of seronegative neuromyelitis optica (NMO). (3) A 23-year-old female with overweight and headache had bilateral optic disc swelling. With OCT and lumbar puncture, idiopathic intracranial hypertension (IIH) was excluded. Further investigation showed positive antibody for myelin oligodendrocyte glycoprotein (MOG). Conclusions: These three cases illustrate the importance of using OCT to facilitate quick, objective and accurate diagnosis of atypical or subclinical ON, and thus proper therapy.

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  • 13.
    Kits, Annika
    et al.
    Karolinska Univ Hosp, Sweden.
    Pantalone, Mattia Russel
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Illies, Christopher
    Karolinska Univ Lab, Sweden.
    Antovic, Aleksandra
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Iacobaeus, Ellen
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Fatal Acute Hemorrhagic Encephalomyelitis and Antiphospholipid Antibodies following SARS-CoV-2 Vaccination: A Case Report2022In: Vaccines, E-ISSN 2076-393X, Vol. 10, no 12, article id 2046Article in journal (Refereed)
    Abstract [en]

    Acute hemorrhagic encephalomyelitis (AHEM) is a rare hyperacute form of acute disseminated encephalomyelitis (ADEM). The disease is characterized by fulminant inflammation and demyelination in the brain and spinal cord and is often preceded by an infection or vaccination. This case report presents a 53-year-old male with rheumatoid arthritis and ongoing treatment with methotrexate and etanercept who developed fatal AHEM following the second dose of the COVID-19 vaccine. The disease course was complicated by multiorgan thromboembolic disease and the presence of high/moderate levels of cardiolipin IgG antibodies and anti-beta-2 glycoprotein 1 IgG antibodies suggesting a possible antiphospholipid syndrome. Treatment with immunosuppressive therapies failed to improve the course. The report comprises comprehensive clinical, neuroimaging, and neuropathological findings. The case highlights diagnostic challenges in a patient with several preceding risk factors, including autoimmune disease, immunotherapy, and vaccination, with possible pathophysiological implications. The temporal association with the COVID-19 vaccination may suggest possible causality although evidence cannot be ascertained. Reporting possible adverse events following COVID-19 vaccination is important to identify at-risk populations and to accomplish control of the current pandemic.

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  • 14.
    Gauffin, Helena
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Fast, Thomas
    Inst Appl Econ & Hlth Res, Denmark; Univ Gothenburg, Sweden.
    Komkova, Anastasija
    Inst Appl Econ & Hlth Res, Denmark.
    Berntsson, Shala
    Uppsala Univ, Sweden.
    Boström, Inger
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Uppsala Univ, Sweden.
    Narcolepsy treatment in Sweden: An observational study2022In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 145, no 2, p. 185-192Article in journal (Refereed)
    Abstract [en]

    Objectives To describe the pharmacological treatments (2005-2017) and the healthcare utilization (1997-2016) for patients with narcolepsy in Sweden in order to create a framework for future organizational and economic analyses. Material & Methods Patients of all ages with a diagnosis of narcolepsy registered in the National Patient Registry in specialist care in Sweden were included and information on treatments for narcolepsy was retrieved from The Swedish Prescribed Drug Register. Results We collected 2508 patients with narcolepsy, 43,3% men and 56,7% women and 47,9% were prescribed modafenil, 33,8% metylphenidate and 26,2% amphetamine. In total, 3817 treatments were initiated. Patients treated with amphetamine had a higher mean age. More women than men used modafinil, methylphenidate, amphetamine and antidepressants. The narcolepsy population had more outpatient than inpatient healthcare. Patients treated with sodium oxybate had more outpatient visits than other narcolepsy patients, before and during treatment (p = .00). Conclusions This study gives valuable information on pharmaceutical treatments and healthcare utilization for patients with narcolepsy and can be used to estimate the healthcare cost in the future. Patients with sodium oxybate treatment had more outpatient visits than other patients before and during treatment which may be due to the need to monitor potentially severe side-effects or may indicate that patients with sodium oxybate treatment have a severe disease. The number of included patients was less than expected; however, this may depend on patients escaping our collection of data, which does not contain information from primary care.

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  • 15.
    Gauffin, Helena
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala. Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden; .
    Vigren, Patrick
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Frick, Andreas
    The Beijer Laboratory, Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
    Engström, Maria
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    McAllister, Anita
    Division of Speech Language Pathology, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden; Women's Health and Allied Health Professionals Theme, Medical Unit Speech and Language Pathology, Karolinska University Hospital, Stockholm, Sweden.
    Karlsson, Thomas
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
    Similar Profile and Magnitude of Cognitive Impairments in Focal and Generalized Epilepsy: A Pilot Study2022In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 12, article id 746381Article in journal (Refereed)
    Abstract [en]

    Introduction: Cognitive impairments in epilepsy are not well-understood. In addition, long-term emotional, interpersonal, and social consequences of the underlying disturbances are important to evaluate.

    Purpose: To compare cognitive function including language in young adults with focal or generalized epilepsy. In addition, quality of life and self-esteem were investigated.

    Patients and Methods: Young adults with no primary intellectual disability, 17 with focal epilepsy and 11 with generalized epilepsy participated and were compared to 28 healthy controls. Groups were matched on age (mean = 26 years), sex, and education. Participants were administered a battery of neuropsychological tasks and carried out self-ratings of quality of life, self-esteem, and psychological problems.

    Results: Similar impairments regarding cognitive function were noted in focal and generalized epilepsy. The cognitive domains tested were episodic long-term memory, executive functions, attention, working memory, visuospatial functions, and language. Both epilepsy groups had lower results compared to controls (effect sizes 0.24-1.07). The total number of convulsive seizures was predictive of episodic long-term memory function. Participants with focal epilepsy reported lower quality of life than participants with generalized epilepsy. Lowered self-esteem values were seen in both epilepsy groups and particularly in those with focal epilepsy. Along with measures of cognitive speed and depression, the total number of seizures explained more than 50% of variation in quality of life.

    Conclusion: Interestingly, similarities rather than differences characterized the widespread cognitive deficits that were seen in focal and generalized epilepsy, ranging from mild to moderate. These similarities were modified by quality of life and self-esteem. This study confirms the notion that epilepsy is a network disorder.

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  • 16.
    Roodakker, Kenney Roy
    et al.
    Uppsala Univ, Sweden.
    Ezra, Bisrat
    Uppsala Univ, Sweden.
    Gauffin, Helena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Latini, Francesco
    Uppsala Univ, Sweden.
    Zetterling, Maria
    Uppsala Univ, Sweden.
    Berntsson, Shala
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala. Uppsala Univ, Sweden.
    Ecstatic and gelastic seizures related to the hypothalamus2021In: Epilepsy & Behavior Reports, E-ISSN 2589-9864, Vol. 16, article id 100400Article in journal (Refereed)
    Abstract [en]

    Ecstatic seizures constitute a rare form of epilepsy, and the semiology is diverse. Previously, brain areas including the temporal lobe and the insula have been identified to be involved in clinical expression. The aim of this report is to review changes in ecstatic seizures in a patient before and after operation for a hypothalamic hamartoma, and to scrutinize the relation to gelastic seizures. In this case, the ecstatic seizures disappeared after surgery of the hamartoma but reappeared eleven years later. Clinical information was retrospectively obtained from medical records, interviews, and a questionnaire covering seizure semiology that pertained to ecstatic and gelastic seizures. Our findings imply a possible connection between gelastic and ecstatic seizures, originating from a hypothalamic hamartoma. To our knowledge, this location has not previously been described in ecstatic seizures. Gelastic seizures may in this case be associated with ecstatic seizures. We speculate that patients with ecstatic seizures may have an ictal activation of neuronal networks that involve the insula. Our case may add information to the knowledge concerning ecstatic seizures. (C) 2020 The Authors. Published by Elsevier Inc.

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  • 17.
    Roodakker, Kenney Roy
    et al.
    Uppsala Univ, Sweden.
    Ezra, Bisrat
    Uppsala Univ, Sweden.
    Gauffin, Helena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Latini, Francesco
    Uppsala Univ, Sweden.
    Zetterling, Maria
    Uppsala Univ, Sweden.
    Berntsson, Shala
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Uppsala Univ, Sweden;.
    Erratum to "Ecstatic and gelastic seizures related to the hypothalamus"  [Epilepsy Behav. Rep. 14 (2020) 100358]2021In: Epilepsy & Behavior Reports, E-ISSN 2589-9864, Vol. 15, article id 100399Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 18.
    Ambati, Aditya
    et al.
    Stanford Univ, CA 94304 USA.
    Hillary, Ryan
    Stanford Univ, CA 94304 USA.
    Leu-Semenescu, Smaranda
    Sorbonne Univ, France.
    Ollila, Hanna M.
    Stanford Univ, CA 94304 USA.
    Lin, Ling
    Stanford Univ, CA 94304 USA.
    During, Emmanuel H.
    Stanford Univ, CA 94305 USA; Stanford Univ, CA 94305 USA.
    Farber, Neal
    Kleine Levin Syndrome Fdn, MA 02468 USA.
    Rico, Thomas J.
    Stanford Univ, CA 94304 USA.
    Faraco, Juliette
    Stanford Univ, CA 94304 USA.
    Leary, Eileen
    Stanford Univ, CA 94304 USA.
    Goldstein-Piekarski, Andrea N.
    Stanford Univ, CA 94305 USA; Vet Affairs Palo Alto Hlth Care Syst, CA 94304 USA.
    Huang, Yu-Shu
    Chang Gung Mem Hosp & Univ, Taiwan; Chang Gung Mem Hosp & Univ, Taiwan.
    Han, Fang
    Peking Univ Peoples Hosp, Peoples R China.
    Sivan, Yakov
    Tel Aviv Univ, Israel.
    Lecendreux, Michel
    Hosp Robert Debre, France; Hosp Robert Debre, France.
    Dodet, Pauline
    Sorbonne Univ, France.
    Honda, Makoto
    Tokyo Metropolitan Inst Med Sci, Japan.
    Gadoth, Natan
    Maynei Hayeshua Med Ctr, Israel; Tel Aviv Univ, Israel.
    Nevsimalova, Sona
    Charles Univ Prague, Czech Republic.
    Pizza, Fabio
    Univ Bologna, Italy; IRCCS, Italy.
    Kanbayashi, Takashi
    Univ Tsukuba, Japan.
    Peraita-Adrados, Rosa
    Univ Complutense Madrid, Spain; Univ Complutense Madrid, Spain.
    Leschziner, Guy D.
    Guys Hosp, England; Kings Coll London, England.
    Hasan, Rosa
    Univ Sao Paulo, Brazil.
    Canellas, Francesca
    Hosp Univ Son Espases, Spain.
    Kume, Kazuhiko
    Nagoya City Univ, Japan.
    Daniilidou, Makrina
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Bourgin, Patrice
    Hop Univ Strasbourg, France.
    Rye, David
    Emory Univ, GA 30322 USA.
    Vicario, Jose L.
    Blood Ctr Community Madrid, Spain.
    Hogl, Birgit
    Innsbruck Med Univ, Austria.
    Hong, Seung Chul
    Catholic Univ Korea, South Korea.
    Plazzi, Guiseppe
    Univ Bologna, Italy; IRCCS, Italy.
    Mayer, Geert
    Philipps Univ Marburg, Germany.
    Landtblom, Anne-Marie
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Uppsala Univ, Sweden.
    Dauvilliers, Yves
    Univ Montpellier, France; Univ Montpellier, France.
    Arnulf, Isabelle
    Sorbonne Univ, France.
    Mignot, Emmanuel Jean-Marie
    Stanford Univ, CA 94304 USA.
    Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci2021In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 118, no 12, article id e2005753118Article in journal (Refereed)
    Abstract [en]

    Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 x 10(-9)) within the 3region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R-2 = 0.15; P < 2.0 x 10(-22) at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.

  • 19.
    Landtblom, Anne-Marie
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Uppsala Univ, Sweden.
    Berntsson, Shala G.
    Uppsala Univ, Sweden.
    Boström, Inger
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Iacobaeus, Ellen
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Multiple sclerosis and COVID-19: The Swedish experience2021In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 144, no 3, p. 229-235Article, review/survey (Refereed)
    Abstract [en]

    The COVID-19 pandemic has brought challenges for healthcare management of patients with multiple sclerosis (MS). Concerns regarding vulnerability to infections and disease-modifying therapies (DMTs) and their complications have been raised. Recent published guidelines on the use of DMTs in relation to COVID-19 in MS patients have been diverse between countries with lack of evidence-based facts. In Sweden, there exists a particular interest in anti-CD20 therapy as a possible risk factor for severe COVID-19 due to the large number of rituximab-treated patients off-label in the country. Rapid responses from the Swedish MS Association (SMSS) and the Swedish MS registry (SMSreg) have resulted in national guidelines on DMT use for MS patients and implementation of a COVID-19 module in the SMSreg. Recently updated guidelines also included recommendations on COVID-19 vaccination with regard to the different DMTs. Social distancing policies forced implementation of telemedicine consultation to replace in-person consultations as part of regular MS health care. Patient-reported outcome measures (PROMs) in SMSreg have been useful in this respect. This paper reports our experiences on the progress of national MS health care during the COVID-19 pandemic, in addition to offering an overview of the present scientific context.

  • 20.
    Teljas, Cecilia
    et al.
    Karolinska Inst, Sweden.
    Boström, Inger
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Marrie, Ruth Ann
    Univ Manitoba, Canada.
    Landtblom, Anne-Marie
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Uppsala Univ, Sweden.
    Manouchehrinia, Ali
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hillert, Jan
    Karolinska Inst, Sweden.
    McKay, Kyla A.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Validating the diagnosis of multiple sclerosis using Swedish administrative data in Värmland County2021In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 144, no 6, p. 680-686Article in journal (Refereed)
    Abstract [en]

    Objectives Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system. Identifying MS at the population level is important for disease surveillance and allocation of resources. The Swedish National Patient Registry (NPR) has been used to study the epidemiology of MS, but the accuracy of this resource is not known. We aimed to validate a definition of MS using the Swedish NPR in Varmland County using a longitudinal cohort design. Materials and Methods Data were extracted from the NPR, the Total Population Register, the Swedish MS Register, and medical records for the years 2001-2013. Fifteen algorithms of hospitalizations and clinic visits for MS were developed and compared with findings in medical records, which acted as the "gold standard" definition. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were estimated. Results Of 805 eligible persons identified in the NPR, 763 had MS (94.8%) according to medical records. Of these, 544 (71.3%) were also registered in the SMSreg. The case definition that had a well-balanced sensitivity and specificity required three or more clinic or hospital visits for MS (sensitivity of 85.3% (95% CI: 82.6-87.8) and specificity of 81.0% (95%CI: 65.9-91.4). Conclusions Multiple case definitions with high sensitivity and moderate specificity were found, suggesting that the NPR can be used to accurately identify persons with MS.

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  • 21.
    Berntsson, Shala Ghaderi
    et al.
    Uppsala Univ, Sweden.
    Kristoffersson, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Daniilidou, Makrina
    Uppsala Univ, Sweden.
    Dahl, Niklas
    Uppsala Univ, Sweden.
    Ekstrom, Curt
    Uppsala Univ, Sweden.
    Semnic, Robert
    Uppsala Univ, Sweden.
    Markstrom, Agneta
    Uppsala Univ, Sweden.
    Niemela, Valter
    Uppsala Univ, Sweden.
    Partinen, Markku
    Helsinki Sleep Clin, Finland; Univ Helsinki, Finland.
    Hallbook, Finn
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Uppsala Univ, Sweden.
    Aniridia with PAX6 mutations and narcolepsy2020In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 29, no 6, article id e12982Article in journal (Refereed)
    Abstract [en]

    PAX6 gene mutations cause a variety of eye and central nervous system (CNS) abnormalities. Aniridia is often accompanied by CNS abnormalities such as pineal gland atrophy or hypoplasia, leading to disturbed circadian rhythm and sleep disorders. Less is known on the coincidence of narcolepsy in this patient group. We aimed to find out whether the circadian rhythm or sleep-wake structure was affected in patients with aniridia. Four members of a family segregating with congenital aniridia in two generations were included in the study. The patients were subjected to genetic testing for a PAX6 mutation, multiple sleep latency test, whole-brain magnetic resonance imaging (MRI), hypocretin-1 in cerebrospinal fluid, and Human Leukocyte Antigen DQ beta1*06:02. All four members were heterozygous for the pathogenic c.959-1Gamp;gt;A mutation in the PAX6 gene. Sleep disturbance was observed in all family members. The index patient was diagnosed with narcolepsy. MRI showed a hypoplastic pineal gland in all members. We describe the first case of a patient with PAX6 haploinsufficiency, aniridia and pineal gland hypoplasia diagnosed with narcolepsy type-1, suggesting a complex sleep disorder pathogenesis.

  • 22.
    Roodakker, Kenney Roy
    et al.
    Uppsala Univ, Sweden.
    Ezra, Bisrat
    Uppsala Univ, Sweden.
    Gauffin, Helena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Latini, Francesco
    Uppsala Univ, Sweden.
    Zetterling, Maria
    Uppsala Univ, Sweden.
    Berntsson, Shala
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala. Uppsala Univ, Sweden.
    Ecstatic and gelastic seizures relate to the hypothalamus2020In: Epilepsy & Behavior Reports, E-ISSN 2589-9864, Vol. 14, article id 100358Article in journal (Refereed)
    Abstract [en]

    Ecstatic seizures constitute a rare form of epilepsy, and the semiology is diverse. Previously, brain areas including the temporal lobe and the insula have been identified to be involved in clinical expression. The aim of this report is to review changes in ecstatic seizures in a patient before and after operation of a hypothalamic hamartoma, and to scrutinize the relation to gelastic seizures. In this case, the ecstatic seizures disappeared after surgery of the hamartoma but reappeared eleven years later. Clinical information was retrospectively obtained from medical records, interviews, and a questionnaire covering seizure semiology that pertained to ecstatic and gelastic seizures. Our findings imply a possible connection between gelastic and ecstatic seizures, originating from a hypothalamic hamartoma. To our knowledge, this location has not previously been described in ecstatic seizures. Gelastic seizures may in this case were associated with ecstatic seizures. We speclate patients with ecstatic seizures may have an ictal activation of neuronal networks that involves the insula. Our case may add information to the growing knowledge concerning ecstatic seizures. (C) 2020 The Author(s). Published by Elsevier Inc.

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  • 23.
    Bolin, Kristian
    et al.
    Univ Gothenburg, Sweden.
    Niska, Per-Ake
    AOP Orphan Pharmaceut AG, Sweden.
    Pirhonen, Laura
    Univ Gothenburg, Sweden.
    Wasling, Pontus
    Gothenburg Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Uppsala Univ, Sweden.
    The cost utility of pitolisant as narcolepsy treatment2020In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 141, no 4, p. 301-310Article in journal (Refereed)
    Abstract [en]

    Objectives The cost-effectiveness of available pharmacological treatments for narcolepsy is largely unknown. Available pharmacological treatments are associated with tolerability, abuse, and adherence issues. Pitolisant is the first inverse agonist of the histamine H3 receptor to be prescribed for the treatment of narcolepsy with and without cataplexy. Studies suggest that pitolisant is both as effective as previously introduced drugs and is associated with fewer adverse effects. The objective in this study was to estimate the cost-effectiveness of pitolisant as monotherapy, and pitolisant as an adjunctive treatment to modafinil, compared with standard treatment. Materials amp; Methods Calculations were performed using a Markov model with a 50-year time horizon. Healthcare utilization and quality-adjusted life years (QALYs) for each treatment alternative were calculated assuming no treatment effect on survival. Probabilistic sensitivity analyses were performed for treatment effectiveness and healthcare cost parameters. Results The cost per additional quality-adjusted life year was estimated at SEK 356 337 (10 SEK approximate to 1 Euro) for pitolisant monotherapy, and at SEK 491 128 for pitolisant as an adjunctive treatment, as compared to standard treatment. The cost-effectiveness measure was demonstrated to be particularly sensitive to the assumptions made concerning indirect effects on total healthcare utilization and the pitolisant treatment cost. Conclusions The incremental cost-effectiveness ratios were below the unofficial willingness-to-pay threshold at SEK 500 000. The estimated costs per additional QALY obtained here are likely to overestimate the true cost-effectiveness ratio since significant potential indirect effects-pertaining both to labor-market and household-related productivity-of treatment are not taken into account.

  • 24.
    Morales Drissi, Natasha
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Szakacs, Attila
    Univ Gothenburg, Sweden.
    Witt, Suzanne Tyson
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Wretman, Anna
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Stahlbrandt, Henriettae
    Highland Hosp, Sweden.
    Darin, Niklas
    Univ Gothenburg, Sweden.
    Hallbook, Tove
    Univ Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping. Uppsala Univ, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Corrigendum: Altered Brain Microstate Dynamics in Adolescents With Narcolepsy (vol 10, 369, 2016)2019In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 13, article id 385Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 25.
    Berntsson, Shala G.
    et al.
    Uppsala Univ, Sweden.
    Gauffin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Melberg, Atle
    Uppsala Univ, Sweden.
    Holtz, Anders
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala Univ, Sweden.
    Inherited Ataxia and Intrathecal Baclofen for the Treatment of Spasticity and Painful Spasms2019In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 97, no 1, p. 18-23Article in journal (Refereed)
    Abstract [en]

    Background: Intrathecal baclofen (ITB) treatment is considered a powerful tool in the management of severe spasticity in neurological conditions such as multiple sclerosis, cerebral palsy, and traumatic spinal cord and brain injury. 

    Objectives: The objective of this study was to assess the effectiveness of the ITB in patients with inherited ataxia suffering from severe painful spasms and/or spasticity. 

    Method: A total of 5 patients with spinocerebellar ataxia 3 or 7 or Friedreich’s ataxia were included in this observational multicenter study. The patients were interviewed and completed outcome measures assessing pain (The Brief Pain Inventory), fatigue (Fatigue Severity Scale), and life satisfaction (LiSAT-9) before and 1 year after the treatment. Spasticity (Modified Ashworth Scale) and spasm frequency (SPFS) were measured objectively for each patient. 

    Results: The mean treatment time was 1.9 years. Evaluation of established standard forms revealed symptomatic relief from spasticity, spasms, pain, and fatigue in addition to improved body posture, sleep, and life satisfaction after ITB treatment. 

    Conclusions: We report the potential beneficial effects of ITB treatment in patients with inherited ataxia who also suffer from spasticity/spasms. ITB treatment indication in neurological disorders allows for extension to the treatment of spasticity/ spasms in patients with hereditary ataxia.

  • 26.
    Landtblom, Anne-Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping. Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Kristoffersson, A.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Boström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Organic solvent exposure as a risk factor for multiple sclerosis: An updated review2019In: Revue neurologique (Paris), ISSN 0035-3787, E-ISSN 2213-0004, Vol. 175, no 10, p. 625-630Article, review/survey (Refereed)
    Abstract [en]

    Organic solvents exposure has for a long time been suspected as a risk factor for developing multiple sclerosis. The evidence, containing case reports, case-control studies and cohort studies has been contradictory. An early meta-analysis, however, pointed to a doubled risk for MS. Recent major case-control studies confirm this, but also have elucidated the risk pattern, being dependent on another risk factor, i.e. smoking.

  • 27.
    Morales Drissi, Natasha
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Wessen, Alexander
    Linköping University.
    Szakacs, Attila
    Univ Gothenburg, Sweden.
    darin, Niklas
    Univ Gothenburg, Sweden.
    Hallbook, Tove
    Univ Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala Univ, Sweden.
    Gauffin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin2019In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 23, article id 101875Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate structural changes in the brain stem of adolescents with narcolepsy, a disorder characterized by excessive daytime sleepiness, fragmented night-time sleep, and cataplexy. For this purpose, we used quantitative magnetic resonance imaging to obtain R1 and R2 relaxation rates, proton density, and myelin maps in adolescents with narcolepsy (n = 14) and healthy controls (n = 14). We also acquired resting state functional magnetic resonance imaging (fMRI) for brainstem connectivity analysis. We found a significantly lower R2 in the rostral reticular formation near the superior cerebellar peduncle in narcolepsy patients, family wise error corrected p = .010. Narcolepsy patients had a mean R2 value of 1.17 s(-1) whereas healthy controls had a mean R2 of 1.31 s(-1), which was a large effect size with Cohen d = 4.14. We did not observe any significant differences in R1 relaxation, proton density, or myelin content. The sensitivity of R2 to metal ions in tissue and the transition metal ion chelating property of neuromelanin indicate that the R2 deviant area is one of the neuromelanin containing nuclei of the brain stem. The close proximity and its demonstrated involvement in sleep-maintenance, specifically through orexin projections from the hypothalamus regulating sleep stability, as well as the results from the connectivity analysis, suggest that the observed deviant area could be the locus coeruleus or other neuromelanin containing nuclei in the proximity of the superior cerebellar peduncle. Hypothetically, the R2 differences described in this paper could be due to lower levels of neuromelanin in this area of narcolepsy patients.

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  • 28.
    Witt, Suzanne T.
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Drissi, Natasha Morales
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Wretman, Anna
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Szakács, Attila
    Sahlgrenska Academy, University of Gothenburg, Sweden.
    Hallböök, Tove
    Sahlgrenska Academy, University of Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping. Uppsala University, Uppsala, Sweden.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Evidence for cognitive resource imbalance in adolescents with narcolepsy2018In: Brain Imaging and Behavior, ISSN 1931-7557, E-ISSN 1931-7565, Vol. 12, no 2, p. 411-424Article in journal (Refereed)
    Abstract [en]

    The study investigated brain activity changes during performance of a verbal working memory task in a population of adolescents with narcolepsy. Seventeen narcolepsy patients and twenty healthy controls performed a verbal working memory task during simultaneous fMRI and EEG acquisition. All subjects also underwent MRS to measure GABA and Glutamate concentrations in the medial prefrontal cortex. Activation levels in the default mode network and left middle frontal gyrus were examined to investigate whether narcolepsy is characterized by an imbalance in cognitive resources. Significantly increased deactivation within the default mode network during task performance was observed for the narcolepsy patients for both the encoding and recognition phases of the task. No evidence for task performance deficits or reduced activation within the left middle frontal gyrus was noted for the narcolepsy patients. Correlation analyses between the spectroscopy and fMRI data indicated that deactivation of the anterior aspect of the default mode in narcolepsy patients correlated more with increased concentrations of Glutamate and decreased concentrations of GABA. In contrast, deactivation in the default mode was correlated with increased concentrations of GABA and decreased concentrations of Glutamate in controls. The results suggested that narcolepsy is not characterized by a deficit in working memory but rather an imbalance of cognitive resources in favor of monitoring and maintaining attention over actual task performance. This points towards dysregulation within the sustained attention system being the origin behind self-reported cognitive difficulties in narcolepsy.

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  • 29.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Latini, Francesco
    Department of Neuroscience, Section of Neurosurgery, Uppsala University, Uppsala, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Department of Neuroscience, Section of Neurology, Uppsala University, Uppsala, Sweden.
    Neuroimaging in the Kleine-Levin Syndrome2018In: Current Neurology and Neuroscience Reports, ISSN 1528-4042, E-ISSN 1534-6293, Vol. 18, no 9, article id 58Article, review/survey (Refereed)
    Abstract [en]

    The purpose was to review the most recent literature on neuroimaging in the Kleine-Levin syndrome (KLS). We aimed to investigate if frontotemporal and thalamic dysfunction are key KLS signatures, and if recent research indicates other brain networks of interest that elucidate KLS symptomatology and aetiology. In a comprehensive literature search, we found 12 original articles published 2013-2018. Most studies report deviations related to cerebral perfusion, glucose metabolism, or blood-oxygen-level-dependent responses in frontotemporal areas and/or the thalamus. Studies also report dysfunction in the temporoparietal junction and the oculomotor network that also were related to clinical parameters. We discuss these findings based on recent research on thalamocortical networks and brain stem white matter tracts. The hypothesis of frontotemporal and thalamic involvement in KLS was confirmed, and additional findings in the temporoparietal junction and the oculomotor system suggest a broader network involvement, which can be investigated by future high-resolution and multimodal imaging.

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  • 30.
    Wesnes, Kristin
    et al.
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Myhr, Kjell-Morten
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Riise, Trond
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Cortese, Marianna
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Pugliatti, Maura
    Univ Bergen, Norway; Univ Ferrara, Italy.
    Boström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala Univ, Sweden.
    Wolfson, Christina
    McGill Univ, Canada.
    Bjornevik, Kjetil
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Physical activity is associated with a decreased multiple sclerosis risk: The EnvIMS study2018In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, no 2, p. 150-157Article in journal (Refereed)
    Abstract [en]

    Background: The lifestyle factors smoking and obesity have been associated with the risk of multiple sclerosis (MS). Physical activity (PA) may also be of importance. Objective: To examine the association between PA and MS risk in Italy, Norway, and Sweden and to evaluate the possible influence by established risk factors. Methods: In this case-control study, 1904 cases and 3694 controls were asked to report their average weekly amounts of light and vigorous PA during adolescence on a scale ranging from none to more than 3 hours activity. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for potential confounders. Results: Vigorous PA was inversely associated with MS risk in the pooled analysis (p-trend amp;lt; 0.001) with an age-and sex-adjusted OR of 0.74 (95% CI: 0.63-0.87) when comparing the highest and lowest levels. Adjusting for outdoor activity, infectious mononucleosis, body size, and smoking yielded similar results. The association was present in all countries and was not affected by exclusion of patients with early disease onset. Light PA was not associated with the risk of MS. Conclusion: Our findings suggest that vigorous PA can modify the risk of developing MS independent of established risk factors.

  • 31.
    Berntsson, S. G.
    et al.
    Uppsala Univ, Sweden.
    Kristoffersson, A.
    Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Boström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Feresiadou, A.
    Uppsala Univ, Sweden.
    Burman, J.
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden Outlier or predecessor?2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 327-331Article in journal (Refereed)
    Abstract [en]

    ObjectivesOff-label use of rituximab to treat MS patients in Sweden is high, and the need for long-term safety data may not be met. Our objectives were to assess the rate of rituximab prescription in patients with multiple sclerosis in Sweden and, in addition, to evaluate the safety of rituximab in a single centre for patients with multiple sclerosis. Material and MethodsReview of the Swedish MS register was performed to study the number of MS patients treated with rituximab during the last 6years. Investigation also included a retrospective review of medical files in search for possible side effects/adverse events in all adult patients with MS treated with rituximab at Uppsala University Hospital. ResultsPresently, in Sweden the rate of rituximab prescriptions in relation to other annually started of disease- modifying drugs in MS is 53.5%. ConclusionsThe share of MS patients in Sweden who are treated with rituximab is very high, and also rapidly increasing. Taken into account the off-label use, cases with adverse medical conditions that could possibly be related to rituximab use should be reported thoroughly.

  • 32.
    Morales Drissi, Natasha
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). AMRA Med AB, Linkoping, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala Univ, Sweden.
    Szakacs, Attila
    Univ Gothenburg, Sweden.
    Hallbook, Tove
    Univ Gothenburg, Sweden.
    Darin, Niklas
    Univ Gothenburg, Sweden.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). AMRA Med AB, Linkoping, Sweden.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). AMRA Med AB, Linkoping, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Unexpected Fat Distribution in Adolescents With Narcolepsy2018In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 9, article id 728Article in journal (Refereed)
    Abstract [en]

    Narcolepsy type 1 is a chronic sleep disorder with significantly higher BMI reported in more than 50% of adolescent patients, putting them at a higher risk for metabolic syndrome in adulthood. Although well-documented, the body fat distribution and mechanisms behind weight gain in narcolepsy are still not fully understood but may be related to the loss of orexin associated with the disease. Orexin has been linked to the regulation of brown adipose tissue (BAT), a metabolically active fat involved in energy homeostasis. Previous studies have used BMI and waist circumference to characterize adipose tissue increases in narcolepsy but none have investigated its specific distribution. Here, we examine adipose tissue distribution in 19 adolescent patients with narcolepsy type 1 and compare them to 17 of their healthy peers using full body magnetic resonance imaging (MRI). In line with previous findings we saw that the narcolepsy patients had more overall fat than the healthy controls, but contrary to our expectations there were no group differences in supraclavicular BAT, suggesting that orexin may have no effect at all on BAT, at least under thermoneutral conditions. Also, in line with previous reports, we observed that patients had more total abdominal adipose tissue (TAAT), however, we found that they had a lower ratio between visceral adipose tissue (VAT) and TAAT indicating a relative increase of subcutaneous abdominal adipose tissue (ASAT). This relationship between VAT and ASAT has been associated with a lower risk for metabolic disease. We conclude that while weight gain in adolescents with narcolepsy matches that of central obesity, the lower VAT ratio may suggest a lower risk of developing metabolic disease.

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  • 33.
    Ghaderi Berntsson, Shala
    et al.
    Uppsala University, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala University, Sweden.
    Flensner, Gullvi
    University of West, Sweden.
    Cerebellar ataxia and intrathecal baclofen therapy: Focus on patients experiences2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 6, article id e0180054Article in journal (Refereed)
    Abstract [en]

    Elucidating patients A experiences of living with chronic progressive hereditary ataxia and the symptomatic treatment with intrathecal baclofen (ITB) is the objective of the current study. A multicenter qualitative study with four patients included due to the rare combination of hereditary ataxia and ITB therapy was designed to elucidate participants experiences through semi-structured interviews. The transcribed text was analyzed according to content analysis guidelines. Overall we identified living in the present/taking one day at a time as the main theme covering the following categories: 1) Uncertainty about the future as a consequence of living with a hereditary disease; The disease; 2) Impact on life as a whole, 3) Influence on personal life in terms of feeling forced to terminate employment, 4) Limiting daily activities, and 5) ITB therapy, advantages, and disadvantages. Uncertainty about the future was the category that affected participants personal life, employment, and daily activities. The participants experience of receiving ITB therapy was expressed in terms of improved quality of life due to better body position and movement as well as better sleep and pain relief.

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  • 34.
    Björnevik, Kjetil
    et al.
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Riise, Trond
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Boström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Casetta, Ilaria
    University of Ferrara, Italy.
    Cortese, Marianna
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Granieri, Enrico
    University of Ferrara, Italy.
    Holmoy, Trygve
    University of Oslo, Norway; Akershus University Hospital, Norway.
    Kampman, Margitta T.
    University Hospital North Norway, Norway.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala University, Sweden.
    Magalhaes, Sandra
    McGill University, Canada.
    Pugliatti, Maura
    University of Bergen, Norway; University of Ferrara, Italy.
    Wolfson, Christina
    McGill University, Canada; McGill University, Canada.
    Myhr, Kjell-Morten
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Negative interaction between smoking and EBV in the risk of multiple sclerosis: The EnvIMS study2017In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 7, p. 1018-1024Article in journal (Refereed)
    Abstract [en]

    Background: Results from previous studies on a possible interaction between smoking and Epstein-Barr virus (EBV) in the risk of multiple sclerosis (MS) are conflicting. Objectives: To examine the interaction between smoking and infectious mononucleosis (IM) in the risk of MS. Methods: Within the case-control study on Environmental Factors In Multiple Sclerosis (EnvIMS), 1904 MS patients and 3694 population-based frequency-matched healthy controls from Norway, Italy, and Sweden reported on prior exposure to smoking and history of IM. We examined the interaction between the two exposures on the additive and multiplicative scale. Results: Smoking and IM were each found to be associated with an increased MS risk in all three countries, and there was a negative multiplicative interaction between the two exposures in each country separately as well as in the pooled analysis (p=0.001). Among those who reported IM, there was no increased risk associated with smoking (odds ratio (OR): 0.95, 95% confidence interval (CI): 0.66-1.37). The direction of the estimated interactions on the additive scale was consistent with a negative interaction in all three countries (relative excess risk due to interaction (RERI): -0.98, 95% CI: -2.05-0.15, p=0.09). Conclusion: Our findings indicate competing antagonism, where the two exposures compete to affect the outcome.

  • 35.
    Bolin, K.
    et al.
    University of Gothenburg, Sweden.
    Berggren, F.
    UCB Pharma, Denmark.
    Berling, P.
    UCB Pharma, Denmark.
    Morberg, S.
    UCB Pharma, Denmark.
    Gauffin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala. Uppsala University, Sweden.
    Patterns of antiepileptic drug prescription in Sweden: A register-based approach2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, no 5, p. 521-527Article in journal (Refereed)
    Abstract [en]

    Objectives: To determine drug utilization pathways from the incident healthcare visit due to epilepsy and three years onward. Material and methods: Anti-epileptic drug utilization was calculated using individual information on inpatient- and outpatient care utilization and drug sales. Throughout, we used national register information pertaining to pharmaceutical sales linked to diagnosis-related healthcare utilization. Information on pharmaceutical sales was collected for the 2007-2013 period. Results: For the entire studied period, a majority of new patients with epilepsy were initiated on anti-epileptic drug treatment with a monotherapy (98%); most of these patients remained on that first treatment (64%). The three most frequently prescribed drugs accounted for 72% of the initiated AED treatments. Patients with epilepsy (ICD-10: G40/41) were most commonly prescribed carbamazepine, lamotrigine and valproate. The most common second-line monotherapy was levetiracetam. About 12% of new patients with epilepsy who were initiated on AED treatment during the period eventually switched to an add-on therapy. The proportion of patients who were initiated on treatment with carbamazepine or valproate decreased, and the proportion of patients who remained on their initial monotherapy increased between 2007 and 2013. Conclusions: A limited number of anti-epileptic drugs accounted for the treatment of a majority of new patients with epilepsy (carbamazepine, lamotrigine and valproate accounted for more than 70%). Add-on therapies showed the same pattern, as the most frequently prescribed add-on regimens were the same ones that accounted for most of the monotherapies. There was a tendency towards fewer patients being initiated on AED treatment with either carbamazepine or valproate.

  • 36.
    Morales Drissi, Natasha
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Szakacs, Attila
    University of Gothenburg, Sweden.
    Witt, Suzanne
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Wretman, Anna
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Ståhlbrandt, Henriettae
    Highland Hospital, Sweden.
    Darin, Niklas
    University of Gothenburg, Sweden.
    Hallbook, Tove
    University of Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Altered Brain Microstate Dynamics in Adolescents with Narcolepsy2016In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 10, no 369Article in journal (Refereed)
    Abstract [en]

    Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13-20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional fMRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics.

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  • 37.
    Zetterling, Maria
    et al.
    Uppsala University, Sweden; Uppsala University Hospital, Sweden.
    Roodakker, Kenney R.
    Uppsala University, Sweden.
    Ghaderi Berntsson, Shala
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Edqvist, Per-Henrik
    Uppsala University, Sweden.
    Latini, Francesco
    Uppsala University, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Ponten, Fredrik
    Uppsala University, Sweden.
    Alafuzoff, Irina
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Smits, Anja
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden; Danish Epilepsy Centre, Denmark.
    Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data2016In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 125, no 5, p. 1155-1166Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Magnetic resonance imaging tends to underestimate the extent of diffuse low-grade gliomas (DLGGs). With the aim of studying the presence of tumor cells outside the radiological border, the authors developed a method of correlating MRI findings with histological data in patients with suspected DLGGs in whom en bloc resections were performed. METHODS Five patients with suspected DLGG suitable for en bloc resection were recruited from an ongoing prospective study. Sections of the entire tumor were immunostained with antibodies against mutated IDH1 protein (IDH1-R132H). Magnetic resonance images were coregistered with corresponding IDH1 images. The growth pattern of tumor cells in white and gray matter was assessed in comparison with signal changes on corresponding MRI slices. RESULTS Neuropathological assessment revealed DLGG in 4 patients and progression to WHO Grade III glioma in 1 patient. The tumor core consisted of a high density of IDH1-R132H positive tumor cells and was located in both gray and white matter. Tumor cells infiltrated along the peripheral fibers of the white matter tracts. In all cases, tumor cells were found outside the radiological tumor border delineated on T2-FLAIR MRI sequences. CONCLUSIONS The authors present a new method for the coregistration of histological and radiological characteristics of en bloc removed infiltrative brain tumors that discloses tumor invasion at the radiological tumor borders. This technique can be applied to evaluate the sensitivity of alternative imaging methods to detect scattered tumor cells at tumor borders. Accurate methods for detection of infiltrative tumor cells will improve the possibility of performing radical tumor resection. In future studies, the method could also be used for in vivo studies of tumor invasion.

  • 38.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    New hypothesis on pontine-frontal eye field connectivity in Kleine-Levin syndrome2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, no 6, p. 716-719Article in journal (Refereed)
    Abstract [en]

    Previous studies have indicated involvement of the thalamus and the pons in Kleine-Levin syndrome. In the present study, functional connectivity of the thalamus and the pons was investigated in asymptomatic patients with Kleine-Levin syndrome and healthy controls. Twelve patients and 14 healthy controls were investigated by functional magnetic resonance imaging during rest. Resting state images were analysed using seed regions of interest in the thalamus and the pons. The results showed significantly lower functional connectivity between the pons and the frontal eye field in persons with Kleine-Levin syndrome compared with healthy controls. There were no connectivity differences involving the thalamus. Based on these findings, a relation is proposed between the sleep disorder Kleine-Levin syndrome and cerebral control of eye movements, which in turn is related to visual attention and working memory. This hypothesis has to be tested in future studies of oculomotor control in Kleine-Levin syndrome.

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  • 39.
    Jonsson Gauffin, Helena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Flensner, Gullvi
    University of West, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Uppsala University, Sweden.
    Being parents with epilepsy: thoughts on its consequences and difficulties affecting their children2015In: Neuropsychiatric Disease and Treatment, ISSN 1176-6328, E-ISSN 1178-2021, Vol. 11, p. 1291-1298Article in journal (Refereed)
    Abstract [en]

    Objective: Parents with epilepsy can be concerned about the consequences of epilepsy affecting their children. The aim of this paper is to describe aspects of what it means being a parent having epilepsy, focusing the parents perspectives and their thoughts on having children. Methods: Fourteen adults aged 18-35 years with epilepsy and subjective memory decline took part in focus-group interviews. The interviews were conducted according to a semi-structured guideline. Material containing aspects of parenthood was extracted from the original interviews and a secondary analysis was done according to a content-analysis guideline. Interviews with two parents for the Swedish book Leva med epilepsi [To live with epilepsy] by AM Landtblom (Stockholm: Bilda ide; 2009) were analyzed according to the same method. Results: Four themes emerged: (1) a persistent feeling of insecurity, since a seizure can occur at any time and the child could be hurt; (2) a feeling of inadequacy - of not being able to take full responsibility for ones child; (3) acknowledgment that ones children are forced to take more responsibility than other children do; and (4) a feeling of guilt - of not being able to fulfill ones expectations of being the parent one would like to be. Conclusion: The parents with epilepsy are deeply concerned about how epilepsy affects the lives of their children. These parents are always aware that a seizure may occur and reflect on how this can affect their child. They try to foresee possible dangerous situations and prevent them. These parents were sad that they could not always take full responsibility for their child and could not live up to their own expectations of parenthood. Supportive programs may be of importance since fear for the safety of the child increases the psychosocial burden of epilepsy. There were also a few parents who did not acknowledge the safety issue of their child - the authors believe that it is important to identify these parents and provide extra information and support to them.

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  • 40.
    Wesnes, Kristin
    et al.
    University of Bergen/The Norwegian MS Competence Centre, Haukeland University Hospital, Norway.
    Riise, Trond
    University of Bergen/The Norwegian MS Competence Centre, Haukeland University Hospital, Norway.
    Casetta, Ilaria
    Section of Clinical Neurology, University of Ferrara, Italy.
    Drulovic, Jelena
    Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia.
    Granieri, Enrico
    Section of Clinical Neurology, University of Ferrara, Italy.
    Holmøy, Trygve
    Institute of Clinical Medicine, Faculty of Medicine, University of Oslo/Akershus University Hospital, Norway.
    Kampman, Margitta T
    University of Tromsø/University Hospital of North Norway, Norway.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lauer, Klaus
    Darmstadt, Germany.
    Lossius, Andreas
    Institute of Clinical Medicine, Faculty of Medicine, University of Oslo/Institute of Immunology, Oslo University .
    Magalhaes, Sandra
    Department of Epidemiology and Biostatistics and occupational health, McGill University, Montreal, Canada.
    Pekmezovic, Tatjana
    Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Serbia.
    Bjørnevik, Kjetil
    University of Bergen/The Norwegian MS Competence Centre, Haukeland University Hospital, Norway.
    Wolfson, Christina
    Research institute of the McGill University Health Centre, Montreal, Canada.
    Pugliatti, Maura
    University of Bergen, Norway/ Department of Clinical and Experimental Medicine, University of Sassari, Italy.
    Myhr, Kjell-Morten
    The Norwegian MS Competence Centre, Haukeland University Hospital/The KG Jebsen Centre for MS-Research, University of Bergen, Norway.
    Body size and the risk of multiple sclerosis in Norway and Italy: The EnvIMS study.2015In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, no 4, p. 388-395Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obesity may be a risk factor for developing multiple sclerosis (MS).

    OBJECTIVE: We examined if body size influences the risk of MS in a population-based, case control study.

    METHODS: A total of 953 cases and 1717 controls from Norway and 707 cases and 1333 controls from Italy reported their body size by choosing a silhouette 1 to 9 (largest) every fifth year from age 5 to 30 and at time of study. The body size-related MS risk was defined by odds ratios (ORs) in logistic regression analyses adjusting for age, smoking and outdoor activity.

    RESULTS: In Norway a large body size (silhouettes 6-9) compared to silhouette 3 increased the risk of MS, especially at age 25 (OR 2.21; 95% CI 1.09-4.46 for men and OR 1.43; 95% CI 0.90-2.27 for women). When comparing silhouette 9 to 1, we found a significant dose-response from age 10 until age 30 peaking at age 25 (sex-adjusted OR 2.83; 95% CI 1.68-4.78). The association was present for at least 15 years prior to disease onset. No significant associations were found in Italy.

    CONCLUSIONS: Obesity from childhood until young adulthood is a likely risk factor for MS with a seemingly stronger effect in Norway than in Italy.

  • 41.
    Landtblom, Anne-Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Brain circuitries involved in sleep disorders2015In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 6, no UNSP 66Article in journal (Refereed)
    Abstract [en]

    n/a

  • 42.
    Boström, Inger
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala University, Sweden.
    Does the changing sex ratio of multiple sclerosis give opportunities for intervention?2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, p. 42-45Article, review/survey (Refereed)
    Abstract [en]

    In several international studies, an increasing women-to-men (w/m) ratio in patients with multiple sclerosis (MS) has been reported. Such sex ratios have been analysed by year of onset or by year of birth. In a Swedish study, data from the Swedish MS register (SMSreg) were used to analyse the w/m ratio in Sweden. The sex ratio was analysed both by year of birth (8834 patients) and by year of onset (9098 patients). No increased w/m ratio was seen in this study. The age-specific sex ratio did not demonstrate any significant changes. However, a new investigation of the sex ratio in Sweden, based on data from all available data sources (19,510 patients), showed a significantly increased w/m ratio of MS in Sweden from 1.70 to 2.67. Environmental factors such as cigarette smoking, hormonal factors and nutrition are of interest in this context, but the cause of the increasing w/m ratio in MS is yet not possible to explain.

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  • 43.
    Ziemssen, Tjalf
    et al.
    Neurol University of Klin Klinikum Carl Gustav Carus, Germany.
    Bajenaru, Ovidiu A.
    Carol Davila University of Medical and Pharm, Romania.
    Carra, Adriana
    Hospital Britanico Buenos Aires, Argentina.
    de Klippel, Nina
    Virga Jessaziekenhuis, Belgium.
    Correia de Sa, Joao
    Hospital Santa Maria, Portugal.
    Edland, Astrid
    Central Hospital Buskerud, Norway.
    Frederiksen, Jette L.
    University of Copenhagen, Denmark.
    Heinzlef, Olivier
    Tenon Hospital, France.
    Karageorgiou, Klimentini E.
    Gen Hospital Athens, Greece.
    Delgado, Rafael H. Lander
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Macias Islas, Miguel A.
    Central University of Guadalajara, Mexico.
    Tubridy, Niall
    Dublin University, Ireland.
    Gilgun-Sherki, Yossi
    Teva Pharmaceut Ind Ltd, Israel.
    Erratum to: A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial2015In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 262, no 1, p. 248-248Article in journal (Other academic)
    Abstract [en]

    n/a

  • 44.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Swedish Institute for Disability Research.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Craig, Arthur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Barrow Neurol Institute, AZ 85013 USA.
    Evidence of conjoint activation of the anterior insular and cingulate cortices during effortful tasks2015In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 8, no 1071Article in journal (Refereed)
    Abstract [en]

    The ability to perform effortful tasks is a topic that has received considerable interest in the research of higher functions of the human brain. Neuroimaging studies show that the anterior insular and the anterior cingulate cortices are involved in a multitude of cognitive tasks that require mental effort. In this study, we investigated brain responses to effort using cognitive tasks with task-difficulty modulations and functional magnetic resonance imaging (fMRI). We hypothesized that effortful performance involves modulation of activation in the anterior insular and the anterior cingulate cortices, and that the modulation correlates with individual performance levels. Healthy participants performed tasks probing verbal working memory capacity using the reading span task, and visual perception speed using the inspection time task. In the fMRI analysis, we focused on identifying effort-related brain activation. The results showed that working memory and inspection time performances were directly related. The bilateral anterior insular and anterior cingulate cortices showed significantly increased activation during each task with common portions that were active across both tasks. We observed increased brain activation in the right anterior insula and the anterior cingulate cortex in participants with low working memory performance. In line with the reported results, we suggest that activation in the anterior insular and cingulate cortices is consistent with the neural efficiency hypothesis (Neubauer).

  • 45.
    Bolin, K.
    et al.
    University of Gothenburg, Sweden; University of Gothenburg, Sweden.
    Berggren, F.
    UCB Pharma, Denmark.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Prevalence and cost of epilepsy in Sweden - a register-based approach2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 131, no 1, p. 37-44Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo estimate the prevalence of epilepsy, costs associated with in- and outpatient care, drug utilization and productivity losses due to epilepsy in Sweden for the years 2005 and 2011. MethodsCost components were calculated using registry data on inpatient- and outpatient-care utilization, drug sales and early pensions granted due to permanent disability and mortality. Moreover, by cross-identification of information in healthcare and pharmaceutical registries, we were able to distinguish between pharmaceuticals prescribed for epilepsy and non-epilepsy indications. ResultsThe prevalence of epilepsy was estimated at 0.62% in 2005 and 0.88% in 2011. The total cost of epilepsy increased during the same period, while the per-patient cost decreased from Euro2929 to Euro1729. Direct medical costs accounted for about 36% of the estimated total cost in 2005 and 60% in 2011. The estimated healthcare cost due to epilepsy as a share of total healthcare costs for all illnesses was about the same in 2005 as in 2011 (0.2%), while the corresponding pharmaceutical cost increased from about 0.5% in 2005 to almost 1% in 2011. ConclusionsThe per-patient cost of epilepsy is substantial, implying a significant aggregated cost incurred on society (despite a prevalenceless than1%). Our results suggest that the per-patient pharmaceutical utilization increased, while the per-patient physician visits and hospitalizations decreased, between 2005 and 2011. Moreover, we demonstrate that the 2005 prevalence measure was underestimated the true prevalence in 2005.

  • 46.
    Magalhaes, Sandra
    et al.
    McGill University, Canada; McGill University, Canada.
    Pugliatti, Maura
    University of Sassari, Italy; University of Bergen, Norway; McGill University, Canada.
    Casetta, Ilaria
    University of Ferrara, Italy.
    Drulovic, Jelena
    University of Belgrade, Serbia.
    Granieri, Enrico
    University of Ferrara, Italy.
    Holmoy, Trygve
    University of Oslo, Norway; Akershus University Hospital, Norway.
    Kampman, Margitta T.
    University Hospital North Norway, Norway.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala University, Sweden.
    Lauer, Klaus
    Darmstadt, Germany.
    Myhr, Kjell-Morten
    Haukeland Hospital, Norway; University of Bergen, Norway.
    Parpinel, Maria
    University of Udine, Italy.
    Pekmezovic, Tatjana
    University of Belgrade, Serbia.
    Riise, Trond
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Wolfson, David
    McGill University, Canada.
    Zhu, Bin
    McGill University, Canada.
    Wolfson, Christina
    McGill University, Canada; McGill University, Canada; McGill University, Canada.
    The EnvIMS Study: Design and Methodology of an International Case-Control Study of Environmental Risk Factors in Multiple Sclerosis2015In: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208, Vol. 44, no 3, p. 173-181Article in journal (Refereed)
    Abstract [en]

    Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system, often resulting in significant neurological disability. The causes of MS are not known; however, the incidence of MS is increasing, thereby suggesting that changes in lifestyle and/or environmental factors may be responsible. On this background, the Environmental Risk Factors in MS Study or EnvIMS study was designed to further explore the etiology of MS. The design and methodology are described, providing details to enable investigators to (i) use our experiences to design their own studies; (ii) take advantage of, and build on the methodological work completed for, the EnvIMS study; (iii) become aware of this data source that is available for use by the research community. Methods: EnvIMS is a multinational case-control study, enrolling 2,800 cases with MS and 5,012 population-based controls in Canada, Italy, Norway, Serbia and Sweden. The study was designed to investigate the most commonly implicated risk factors for MS etiology using a self-report questionnaire. Results/Conclusions:The use of a common methodology to study MS etiology across several countries enhances the comparability of results in different geographic regions and research settings, reduces the resources required for study design and enhances the opportunity for data harmonization.

  • 47.
    Ziemssen, Tjalf
    et al.
    Klinikum Carl Gustav Carus, Germany.
    Bajenaru, Ovidiu A.
    Carol Davila University of Medical and Pharm, Romania.
    Carra, Adriana
    Hospital Britanico Buenos Aires, Argentina.
    de Klippel, Nina
    Virga Jessaziekenhuis, Belgium.
    de Sa, Joao C.
    Hospital Santa Mari, Belgium.
    Edland, Astrid
    Central Hospital Buskerud, Norway.
    Frederiksen, Jette L.
    University of Copenhagen, Denmark.
    Heinzlef, Olivier
    Hop Tenon, France.
    Karageorgiou, Klimentini E.
    Gen Hospital Athens, Greece.
    Lander Delgado, Rafael H.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Macias Islas, Miguel A.
    Central University of Guadalajara, Mexico.
    Tubridy, Niall
    Dublin City University, Ireland.
    Gilgun-Sherki, Yossi
    Teva Pharmaceut Ind Ltd, Israel.
    A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial2014In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 261, no 11, p. 2101-2111Article in journal (Refereed)
    Abstract [en]

    Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3-6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81-0.91] before the change to 0.32 (95 % CI 0.26-0.40; p less than 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p less than 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes.

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  • 48.
    Boström, Inger
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Stawiarz, Leszek
    Karolinska Institute, Sweden .
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Age-specific sex ratio of multiple sclerosis in the National Swedish MS Register (SMSreg)2014In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no 4, p. 513-514Article in journal (Other academic)
  • 49.
    Warntjes, Marcel Jan Bertus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Effects of Gadolinium Contrast Agent Administration on Automatic Brain Tissue Classification of Patients with Multiple Sclerosis2014In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 35, no 7, p. 1330-1336Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE:

    The administration of gadolinium contrast agent is a common part of MR imaging examinations in patients with MS. The presence of gadolinium may affect the outcome of automated tissue classification. The purpose of this study was to investigate the effects of the presence of gadolinium on the automatic segmentation in patients with MS by using the synthetic tissue-mapping method.

    MATERIALS AND METHODS:

    A cohort of 20 patients with clinically definite multiple sclerosis were recruited, and the T1 and T2 relaxation times and proton density were simultaneously quantified before and after the administration of gadolinium. Synthetic tissue-mapping was used to measure white matter, gray matter, CSF, brain parenchymal, and intracranial volumes. For comparison, 20 matched controls were measured twice, without gadolinium.

    RESULTS:

    No differences were observed for the control group between the 2 measurements. For the MS group, significant changes were observed pre- and post-gadolinium in intracranial volume (-13 mL, P < .005) and cerebrospinal fluid volume (-16 mL, P < .005) and the remaining, unclassified non-WM/GM/CSF tissue volume within the intracranial volume (+8 mL, P < .05). The changes in the patient group were much smaller than the differences, compared with the controls, which were -129 mL for WM volume, -22 mL for GM volume, +91 mL for CSF volume, 24 mL for the remaining, unclassified non-WM/GM/CSF tissue volume within the intracranial volume, and -126 mL for brain parenchymal volume. No significant differences were observed for linear regression values against age and Expanded Disability Status Scale.

    CONCLUSIONS:

    The administration of gadolinium contrast agent had a significant effect on automatic brain-tissue classification in patients with MS by using synthetic tissue-mapping. The observed differences, however, were much smaller than the group differences between MS and controls.

  • 50.
    Gauffin, Helena
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Epilepsy and violence: case series concerning physical trauma in children of persons with epilepsy2014In: Neuropsychiatric Disease and Treatment, ISSN 1176-6328, E-ISSN 1178-2021, Vol. 10, p. 2183-2189Article in journal (Refereed)
    Abstract [en]

    Historically, epilepsy has been associated with violence, but more recent studies have emphasized genetic and psychosocial factors as more important. The case series presented here aim to highlight the difficult situation the affected children are in. We report on three cases when children have been traumatized and, in one case, even been killed by their parent who was diagnosed with epilepsy. In the first case, we describe a woman with juvenile myoclonic epilepsy who was sentenced to forensic psychiatry care for killing her child. She lived under difficult psychosocial circumstances and a suicide attempt contributed to what happened. The second case describes a man with post-traumatic seizures