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BETA
Landtblom, Anne-MarieORCID iD iconorcid.org/0000-0001-9567-470x
Alternative names
Publications (10 of 80) Show all publications
Herman, S., Niemelä, V., Emami Khoonsari, P., Sundblom, J., Burman, J., Landtblom, A.-M., . . . Kultima, K. (2019). Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington's disease subjects. Scientific Reports, 9, Article ID 4129.
Open this publication in new window or tab >>Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington's disease subjects
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4129Article in journal (Refereed) Published
Abstract [en]

Huntington's disease (HD) is a severe neurological disease leading to psychiatric symptoms, motor impairment and cognitive decline. The disease is caused by a CAG expansion in the huntingtin (HTT) gene, but how this translates into the clinical phenotype of HD remains elusive. Using liquid chromatography mass spectrometry, we analyzed the metabolome of cerebrospinal fluid (CSF) from premanifest and manifest HD subjects as well as control subjects. Inter-group differences revealed that the tyrosine metabolism, including tyrosine, thyroxine, L-DOPA and dopamine, was significantly altered in manifest compared with premanifest HD. These metabolites demonstrated moderate to strong associations to measures of disease severity and symptoms. Thyroxine and dopamine also correlated with the five year risk of onset in premanifest HD subjects. The phenylalanine and the purine metabolisms were also significantly altered, but associated less to disease severity. Decreased levels of lumichrome were commonly found in mutated HTT carriers and the levels correlated with the five year risk of disease onset in premanifest carriers. These biochemical findings demonstrates that the CSF metabolome can be used to characterize molecular pathogenesis occurring in HD, which may be essential for future development of novel HD therapies.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-379886 (URN)10.1038/s41598-019-40186-5 (DOI)000460754600020 ()30858393 (PubMedID)
Funder
Åke Wiberg FoundationEU, Horizon 2020, 654241
Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-03-25Bibliographically approved
Berntsson, S. G., Gauffin, H., Melberg, A., Holtz, A. & Landtblom, A.-M. (2019). Inherited Ataxia and Intrathecal Baclofen for the Treatment of Spasticity and Painful Spasms. Stereotactic and Functional Neurosurgery, 97(1), 18-23
Open this publication in new window or tab >>Inherited Ataxia and Intrathecal Baclofen for the Treatment of Spasticity and Painful Spasms
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2019 (English)In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 97, no 1, p. 18-23Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
KARGER, 2019
Keywords
Intrathecal baclofen treatment, Inherited ataxia, Spasms, Spasticity, Pain
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-384476 (URN)10.1159/000497165 (DOI)000467683300003 ()31050312 (PubMedID)
Available from: 2019-06-05 Created: 2019-06-05 Last updated: 2019-06-05Bibliographically approved
Hallberg, P., Smedje, H., Eriksson, N., Kohnke, H., Daniilidou, M., Öhman, I., . . . Wadelius, M. (2019). Pandemrix-induced narcolepsy is associated with genes related to immunity and neuronal survival. EBioMedicine, 40, 595-604
Open this publication in new window or tab >>Pandemrix-induced narcolepsy is associated with genes related to immunity and neuronal survival
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2019 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 40, p. 595-604Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The incidence of narcolepsy rose sharply after the swine influenza A (H1N1) vaccination campaign with Pandemrix. Narcolepsy is an immune-related disorder with excessive daytime sleepiness. The most frequent form is strongly associated with HLA-DQB1*06:02, but only a minority of carriers develop narcolepsy. We aimed to identify genetic markers that predispose to Pandemrix-induced narcolepsy.

METHODS: We tested for genome-wide and candidate gene associations in 42 narcolepsy cases and 4981 controls. Genotyping was performed on Illumina arrays, HLA alleles were imputed using SNP2HLA, and single nucleotide polymorphisms were imputed using the haplotype reference consortium panel. The genome-wide significance threshold was p < 5 × 10-8, and the nominal threshold was p < 0.05. Results were replicated in 32 cases and 7125 controls. Chromatin data was used for functional annotation.

FINDINGS: Carrying HLA-DQB1*06:02 was significantly associated with narcolepsy, odds ratio (OR) 39.4 [95% confidence interval (CI) 11.3, 137], p = 7.9 × 10-9. After adjustment for HLA, GDNF-AS1 (rs62360233) was significantly associated, OR = 8.7 [95% CI 4.2, 17.5], p = 2.6 × 10-9, and this was replicated, OR = 3.4 [95% CI 1.2-9.6], p = 0.022. Functional analysis revealed variants in high LD with rs62360233 that might explain the detected association. The candidate immune-gene locus TRAJ (rs1154155) was nominally associated in both the discovery and replication cohorts, meta-analysis OR = 2.0 [95% CI 1.4, 2.8], p = 0.0002.

INTERPRETATION: We found a novel association between Pandemrix-induced narcolepsy and the non-coding RNA gene GDNF-AS1, which has been shown to regulate expression of the essential neurotrophic factor GDNF. Changes in regulation of GDNF have been associated with neurodegenerative diseases. This finding may increase the understanding of disease mechanisms underlying narcolepsy. Associations between Pandemrix-induced narcolepsy and immune-related genes were replicated.

Keywords
(MeSH), Autoimmune diseases, Drug-related side effects and adverse reactions, Genetic variation, Genome-wide association study, Glial cell line-derived neurotrophic factor, H1N1 subtype, Influenza A virus, Influenza vaccines, Narcolepsy, Pharmacogenetics, RNA, long noncoding
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-377169 (URN)10.1016/j.ebiom.2019.01.041 (DOI)000460696900067 ()30711515 (PubMedID)
Funder
Swedish Research Council, 521-2011-2440Swedish Research Council, 521-2014-3370Swedish Research Council, 2018-03307Swedish Heart Lung Foundation, 20120557Swedish Heart Lung Foundation, 20140291Swedish Heart Lung Foundation, 20170711Erik, Karin och Gösta Selanders FoundationThuréus stiftelse för främjande av geriatrisk forskningSwedish Research Council, 2017-00641
Available from: 2019-02-15 Created: 2019-02-15 Last updated: 2019-05-13Bibliographically approved
Demirbuker, S. S., Kagström, S., Fält, A., Berglund, A., Hillert, J., Nilsson, P., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 701-702
Open this publication in new window or tab >>A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5)
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2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 701-702Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369957 (URN)000446861401580 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2018-12-17Bibliographically approved
Kagström, S., Fält, A., Demirbuker, S. S., Berglund, A., Hillert, J., Nilsson, P., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of natalizumab (IMSE 1). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 699-700
Open this publication in new window or tab >>A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of natalizumab (IMSE 1)
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2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 699-700Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369956 (URN)000446861401578 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2018-12-18Bibliographically approved
Fält, A., Kågström, S., Demirbuker, S. S., Hillert, J., Nilsson, P., Dahle, C., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 706-707
Open this publication in new window or tab >>A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3)
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2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 706-707Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369958 (URN)000446861401586 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2018-12-17Bibliographically approved
Fält, A., Kagstrom, S., Demirbuker, S. S., Hillert, J., Nilsson, P., Dahle, C., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of fingolimod (IMSE 2). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 696-697
Open this publication in new window or tab >>A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of fingolimod (IMSE 2)
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2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 696-697Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369955 (URN)000446861401574 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2018-12-18Bibliographically approved
Demirbuker, S. S., Kågström, S., Fält, A., Hillert, J., Nilsson, P., Dahle, C., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of teriflunomid (IMSE 4). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 922-923
Open this publication in new window or tab >>A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of teriflunomid (IMSE 4)
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2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 922-923Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369960 (URN)000446861402334 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2018-12-17Bibliographically approved
Witt, S. T., Drissi, N. M., Tapper, S., Wretman, A., Szakács, A., Hallböök, T., . . . Engström, M. (2018). Evidence for cognitive resource imbalance in adolescents with narcolepsy. Brain Imaging and Behavior, 12(2), 411-424
Open this publication in new window or tab >>Evidence for cognitive resource imbalance in adolescents with narcolepsy
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2018 (English)In: Brain Imaging and Behavior, ISSN 1931-7557, E-ISSN 1931-7565, Vol. 12, no 2, p. 411-424Article in journal (Refereed) Published
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.

Keywords
EEG, GABA, MRS, Narcolepsy, Working memory, fMRI
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-318746 (URN)10.1007/s11682-017-9706-y (DOI)000429029000011 ()28321606 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationMedical Research Council of Southeast Sweden (FORSS)
Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2018-06-13Bibliographically approved
Boström, I., Bjornevik, K., Riise, T., Myhre, K.-M. -., Wolfson, C., Pugliatti, M. & Landtblom, A.-M. (2018). Increased risk of MS after organic solvent exposure. Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 139-140
Open this publication in new window or tab >>Increased risk of MS after organic solvent exposure
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2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 139-140Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369954 (URN)000446861400213 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2018-12-18Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9567-470x

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